Disruption of spatiotemporal dependence in dengue transmission by wMel Wolbachia in Yogyakarta, Indonesia

AbstractDengue is known to exhibit focal clustering at the level of the household and neighbourhood, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacterium Wolbachia (wMel-strain) into the Aedes aegypti mosquito population in a randomized controlled trial in Yogyakarta, Indonesia. We analysed 318 serotyped dengue cases and 5,921 test-negative controls with geolocated residence enrolled over 27 months following randomized wMel deployments. We find evidence of spatial dependence up to 300m among the 265 dengue cases (3,083 controls) detected in the untreated trial arm. Spatial dependence is strongest within 50m, with a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds that a pair of individuals enrolled within 30 days and 50m of each other are homotypic dengue cases compared to pairs occurring at any distance. We find no evidence of spatial dependence among the 53 dengue cases (2,838 controls) detected in the wMel-treated arm. This provides compelling evidence that introgression of wMel Wolbachia into Aedes aegypti mosquito populations interrupts focal dengue virus transmission, leading to reduced case incidence.

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Fine scale spatiotemporal clustering of dengue virus transmission in children and Aedes aegypti in rural Thai villages

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2012.05.936 ◽

2012 ◽

Vol 16 ◽

pp. e276

Author(s):

I. Yoon

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Virus Transmission ◽

Fine Scale ◽

Spatiotemporal Clustering

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Fine Scale Spatiotemporal Clustering of Dengue Virus Transmission in Children and Aedes aegypti in Rural Thai Villages

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0001730 ◽

2012 ◽

Vol 6 (7) ◽

pp. e1730 ◽

Cited By ~ 93

Author(s):

In-Kyu Yoon ◽

Arthur Getis ◽

Jared Aldstadt ◽

Alan L. Rothman ◽

Darunee Tannitisupawong ◽

...

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Virus Transmission ◽

Fine Scale ◽

Spatiotemporal Clustering

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Faculty Opinions recommendation of Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732369982.793541519 ◽

2018 ◽

Cited By ~ 2

Author(s):

Jean-Luc Imler ◽

Nelson Martins

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Virus Transmission ◽

Transmission Potential

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A simple cognitive task intervention to prevent intrusive memories after trauma in patients in the Emergency Department: A randomized controlled trial terminated due to COVID-19

BMC Research Notes ◽

10.1186/s13104-021-05572-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Marie Kanstrup ◽

Laura Singh ◽

Katarina E. Göransson ◽

Beau Gamble ◽

Rod S. Taylor ◽

...

Keyword(s):

Emergency Department ◽

Traumatic Event ◽

Cognitive Task ◽

Controlled Trial ◽

Virus Transmission ◽

Computer Game ◽

Similar Time ◽

Intrusive Memories ◽

Randomised Controlled ◽

Simple Cognitive Task

Abstract Objective This randomised controlled trial (RCT) aimed to investigate the effects of a simple cognitive task intervention on intrusive memories ("flashbacks") and associated symptoms following a traumatic event. Patients presenting to a Swedish emergency department (ED) soon after a traumatic event were randomly allocated (1:1) to the simple cognitive task intervention (memory cue + mental rotation instructions + computer game "Tetris" for at least 20 min) or control (podcast, similar time). We planned follow-ups at one-week, 1-month, and where possible, 3- and 6-months post-trauma. Anticipated enrolment was N = 148. Results The RCT was terminated prematurely after recruiting N = 16 participants. The COVID-19 pandemic prevented recruitment/testing in the ED because: (i) the study required face-to-face contact between participants, psychology researchers, ED staff, and patients, incurring risk of virus transmission; (ii) the host ED site received COVID-19 patients; and (iii) reduced flow of patients otherwise presenting to the ED in non-pandemic conditions (e.g. after trauma). We report on delivery of study procedures, recruitment, treatment adherence, outcome completion (primary outcome: number of intrusive memories during week 5), attrition, and limitations. The information presented and limitations may enable our group and others to learn from this terminated study. Trial registration ClinicalTrials.gov: NCT04185155 (04-12-2019)

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Controling the Aedes aegypti mosquito population by Wolbachia-based strategies

10.1063/1.4952181 ◽

2016 ◽

Author(s):

Marat Rafikov ◽

Magno Enrique Mendoza Meza

Keyword(s):

Aedes Aegypti ◽

Mosquito Population

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Sequential Infection of Aedes aegypti Mosquitoes with Chikungunya Virus and Zika Virus Enhances Early Zika Virus Transmission

Insects ◽

10.3390/insects9040177 ◽

2018 ◽

Vol 9 (4) ◽

pp. 177 ◽

Cited By ~ 12

Author(s):

Tereza Magalhaes ◽

Alexis Robison ◽

Michael Young ◽

William Black ◽

Brian Foy ◽

...

Keyword(s):

Aedes Aegypti ◽

Blood Meal ◽

Zika Virus ◽

Chikungunya Virus ◽

Vector Competence ◽

Virus Transmission ◽

Mosquito Vector ◽

Molecular Aspects ◽

Virus Interactions ◽

Sequential Infection

In urban settings, chikungunya, Zika, and dengue viruses are transmitted by Aedes aegypti mosquitoes. Since these viruses co-circulate in several regions, coinfection in humans and vectors may occur, and human coinfections have been frequently reported. Yet, little is known about the molecular aspects of virus interactions within hosts and how they contribute to arbovirus transmission dynamics. We have previously shown that Aedes aegypti exposed to chikungunya and Zika viruses in the same blood meal can become coinfected and transmit both viruses simultaneously. However, mosquitoes may also become coinfected by multiple, sequential feeds on single infected hosts. Therefore, we tested whether sequential infection with chikungunya and Zika viruses impacts mosquito vector competence. We exposed Ae. aegypti mosquitoes first to one virus and 7 days later to the other virus and compared infection, dissemination, and transmission rates between sequentially and single infected groups. We found that coinfection rates were high after sequential exposure and that mosquitoes were able to co-transmit both viruses. Surprisingly, chikungunya virus coinfection enhanced Zika virus transmission 7 days after the second blood meal. Our data demonstrate heterologous arbovirus synergism within mosquitoes, by unknown mechanisms, leading to enhancement of transmission under certain conditions.

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Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1715788115 ◽

2017 ◽

Vol 115 (2) ◽

pp. 361-366 ◽

Cited By ~ 51

Author(s):

Lauren B. Carrington ◽

Bich Chau Nguyen Tran ◽

Nhat Thanh Hoang Le ◽

Tai Thi Hue Luong ◽

Truong Thanh Nguyen ◽

...

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Virus Transmission ◽

Field Testing ◽

Denv Infection ◽

Ho Chi Minh City ◽

Wild Type ◽

Transmission Potential ◽

Blood Meals ◽

Increased Susceptibility

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

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Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1905617116 ◽

2019 ◽

Vol 116 (38) ◽

pp. 19136-19144 ◽

Cited By ~ 17

Author(s):

Giel P. Göertz ◽

Joyce W. M. van Bree ◽

Anwar Hiralal ◽

Bas M. Fernhout ◽

Carmen Steffens ◽

...

Keyword(s):

Aedes Aegypti ◽

Zika Virus ◽

Affinity Purification ◽

Mechanistic Model ◽

Virus Transmission ◽

Protein Translation ◽

Mass Spectrometry Analysis ◽

Small Interfering Rnas ◽

Spectrometry Analysis ◽

Mosquito Infection

Zika virus (ZIKV) is an arthropod-borne flavivirus predominantly transmitted by Aedes aegypti mosquitoes and poses a global human health threat. All flaviviruses, including those that exclusively replicate in mosquitoes, produce a highly abundant, noncoding subgenomic flavivirus RNA (sfRNA) in infected cells, which implies an important function of sfRNA during mosquito infection. Currently, the role of sfRNA in flavivirus transmission by mosquitoes is not well understood. Here, we demonstrate that an sfRNA-deficient ZIKV (ZIKVΔSF1) replicates similar to wild-type ZIKV in mosquito cell culture but is severely attenuated in transmission by Ae. aegypti after an infectious blood meal, with 5% saliva-positive mosquitoes for ZIKVΔSF1 vs. 31% for ZIKV. Furthermore, viral titers in the mosquito saliva were lower for ZIKVΔSF1 as compared to ZIKV. Comparison of mosquito infection via infectious blood meals and intrathoracic injections showed that sfRNA is important for ZIKV to overcome the mosquito midgut barrier and to promote virus accumulation in the saliva. Next-generation sequencing of infected mosquitoes showed that viral small-interfering RNAs were elevated upon ZIKVΔSF1 as compared to ZIKV infection. RNA-affinity purification followed by mass spectrometry analysis uncovered that sfRNA specifically interacts with a specific set of Ae. aegypti proteins that are normally associated with RNA turnover and protein translation. The DEAD/H-box helicase ME31B showed the highest affinity for sfRNA and displayed antiviral activity against ZIKV in Ae. aegypti cells. Based on these results, we present a mechanistic model in which sfRNA sequesters ME31B to promote flavivirus replication and virion production to facilitate transmission by mosquitoes.

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Leukocyte DNA Damage and Wound Infection after Nitrous Oxide Administration

Anesthesiology ◽

10.1097/aln.0b013e31829107b8 ◽

2013 ◽

Vol 118 (6) ◽

pp. 1322-1331 ◽

Cited By ~ 26

Author(s):

Yan Chen ◽

Xiaodong Liu ◽

Christopher H. K. Cheng ◽

Tony Gin ◽

Kate Leslie ◽

...

Keyword(s):

Dna Damage ◽

Nitrous Oxide ◽

Wound Infection ◽

Controlled Trial ◽

Venous Blood ◽

Fold Increase ◽

Postoperative Wound Infection ◽

Double Blind ◽

Postoperative Wound ◽

Oxygen Groups

Abstract Background: Nitrous oxide inactivates methionine synthase and may lead to DNA damage and wound infection. By using single-cell gel electrophoresis (comet assay), the authors determined the effect of nitrous oxide on DNA damage in circulating leukocytes. Methods: In this double-blind, randomized controlled trial, 91 patients undergoing major colorectal surgery were randomized to receive 70% nitrous oxide (n = 31) or nitrous oxide-free anesthesia using 30 (n = 30) or 80% (n = 30) oxygen. Venous blood was collected before and 24 h after surgery. The primary outcome was extent of DNA damage, quantified as the percentage of DNA staining intensity in the comet tail using digital fluorescence microscopy. Incidence of postoperative wound infection was also recorded. Results: Nitrous oxide exposure was associated with a two-fold increase in the percentage of DNA intensity in tail (P = 0.0003), but not in the 30 (P = 0.181) or 80% oxygen groups (P = 0.419). There was a positive correlation between the duration of nitrous oxide exposure and extent of DNA damage, r = 0.33, P = 0.029. However, no correlation was observed in nitrous oxide-free patients. The proportions of postoperative wound infection, using the Centers for Disease Control and Prevention criteria, were 19.4% (6 of 31) in the 70% nitrous oxide group and 6.7% (2 of 30) in both the 30 and 80% oxygen groups, P = 0.21. An increase in DNA damage was associated with a higher risk of wound infection, adjusted odds ratio (95% CIs): 1.19 (1.07–1.34), P = 0.003. Conclusions: Nitrous oxide increased DNA damage compared with nitrous oxide-free anesthesia and was associated with postoperative wound infection.

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