Biology subjects

Althouse, B. M.

Publications and source records attributed to Althouse, B. M..

8 recordsLinked to original sources

bioRxiv2025

Inside-Out: Modeling the link between Zika virus viral dynamics within hosts and transmission to vectors across host species and virus strains

Epidemiological models of mosquito-borne virus transmission often lack accurate estimates of host-to-vector transmission probability. Here, we estimated this probability for two strains of Zika virus (ZIKV)--one sylvatic and one human-endemic--from two monkey species to Aedes albopictus mosquitoes using experimental infection data. Viral dynamics did not differ between monkey species, although one (cynomolgus macaque) is a native ZIKV host and the other (squirrel monkey) a novel host, but differed between strains, with viremia for the human-endemic strain peaking later and lower than the sylvatic strain. Only the sylvatic strain was transmitted to mosquitoes. In mosquitoes, anatomical barriers influence viral progression to salivary glands, complicating host infectiousness estimation. We quantified the probability of viral dissemination to the legs in Ae. albopictus, which increased with host viral load and was higher after feeding on squirrel monkeys than on cynomolgus macaques. We also found a positive relationship between virus titer in mosquito legs and virus detection in saliva after a 14-day extrinsic incubation period. Combining these factors, we found that squirrel monkeys were on average 1.5 times more infectious to Ae. albopictus than cynomolgus macaques. These estimates will help assess ZIKVs potential to establish an enzootic, sylvatic cycle in the Americas.

systems biology↗

bioRxiv2024

Aedes albopictus is not an arbovirus aficionado - Impacts of sylvatic flavivirus infection in vectors and hosts on mosquito engorgement on non-human primates

The contact structure between vertebrate hosts and arthropod vectors plays a key role in the spread of arthropod-borne viruses (arboviruses); thus, it is important to determine whether arbovirus infection of either host or vector alters vector feeding behavior. Here we leveraged a study of the replication dynamics of two arboviruses isolated from their ancestral cycles in paleotropical forests, sylvatic dengue-2 (DENV-2) and Zika (ZIKV), in one non-human primate (NHP) species from the paleotropics (cynomolgus macaques, Macaca fascicularis) and one from the neotropics (squirrel monkeys, Saimiri boliviensis) to test the effect of both vector and host infection with each virus on completion of blood feeding (engorgement) of the mosquito Aedes albopictus. Although mosquitoes were starved and given no choice of hosts, engorgement rates varied dramatically, from 0% to 100%. While neither vector nor host infection systematically affected engorgement, NHP species and body temperature at the time of feeding did. We also interrogated the effect of repeated mosquito bites on cytokine expression and found that epidermal growth factor (EGF) and macrophage migration inhibitory factor (MIF) concentrations were dynamically associated with exposure to mosquito bites. This study highlights the importance of incorporating individual-level heterogeneity of vector biting in arbovirus transmission models.

systems biology↗

bioRxiv2023

Immunologically mediated trade-offs shaping transmission of sylvatic dengue and Zika viruses in native and novel non-human primate hosts

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic cycles involving monkey hosts, spilled over into human transmission, and were translocated to the Americas, creating potential for spillback into neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We exposed native (cynomolgus macaque) or novel (squirrel monkey) hosts to mosquitoes infected with either sylvatic DENV or ZIKV and monitored viremia, natural killer cells, transmission to mosquitoes, cytokines, and neutralizing antibody titers. Unexpectedly, DENV transmission from both host species occurred only when serum viremia was undetectable or near the limit of detection. ZIKV replicated in squirrel monkeys to much higher titers than DENV and was transmitted more efficiently but stimulated lower neutralizing antibody titers. Increasing ZIKV viremia led to greater instantaneous transmission and shorter duration of infection, consistent with a replication-clearance trade-off.

microbiology↗

bioRxiv2020

Ecological processes underlying the emergence of novel enzootic cycles--arboviruses in the neotropics as a case study

Pathogens originating from wildlife (zoonoses) pose a significant public health burden, comprising the majority of emerging infectious diseases. Efforts to control and prevent zoonotic disease have traditionally focused on animal-to-human transmission, or "spillover". However, in the modern era, increasing international mobility and commerce facilitate the spread of infected humans, non-human animals (hereafter animals), and their products worldwide, thereby increasing the risk that zoonoses will be introduced to new geographic areas. Imported zoonoses can potentially spill back to infect local wildlife--a danger magnified by urbanization and other anthropogenic pressures that increase contacts between human and wildlife populations. In this way, humans can function as vectors, dispersing zoonoses from their ancestral enzootic systems to establish reservoirs elsewhere in novel animal host populations. Once established, these enzootic cycles are largely unassailable by standard control measures and have the potential to feed human epidemics. Understanding when and why translocated zoonoses establish novel enzootic cycles requires disentangling ecologically complex and stochastic interactions between the zoonosis, the human population, and the natural ecosystem. We address this challenge by delineating potential ecological mechanisms affecting each stage of enzootic establishment--wildlife exposure, enzootic infection, and persistence--applying existing ecological concepts from epidemiology, invasion biology, and population ecology. We ground our study in the neotropics, where four arthropod-borne viruses (arboviruses) of zoonotic origin--yellow fever, dengue, chikungunya, and Zika viruses--have separately been introduced into the human population. This paper is a step towards developing a framework for predicting and preventing novel enzootic cycles in the face of zoonotic translocations.

ecology↗

bioRxiv2019

Community Engagement during outbreak response: standards, approaches, and lessons from the 2014-2016 Ebola outbreak in Sierra Leone

Summary pointsO_LIThe Social Mobilization Action Consortium (SMAC) was Sierra Leones largest coordinated community engagement initiative during the 2014 - 2016 Ebola outbreak. It worked in all 14 districts in Sierra Leone across >12,000 communities (approximately 70% of all communities), through 2,466 trained Community Mobilizers, a network of 2,000 mosques and churches, and 42 local radio stations.\nC_LIO_LIWe describe SMACs Theory of Change and utilization of the Community-Led Ebola Action (CLEA) approach. We present an extensive dataset of community engagement and monitoring with a focus on over 50,000 SMAC weekly reports collected by Community Mobilizers between December 2014 and September 2015.\nC_LIO_LICommunity engagement and real-time data collection at scale is achievable in the context of a health emergency if adequately structured, managed, coordinated and resourced.\nC_LIO_LIWe describe a correlation between systemic community engagement, community action planning and Ebola-safe behaviors at community-level.\nC_LIO_LIThe SMAC integrated approach demonstrates the scope of data - including surveillance data - that can be generated directly by communities through structured community engagement interventions implemented at scale during an Ebola outbreak.\nC_LIO_LIWe highlight important insights gleaned over time on how to informally integrate social mobilization into community-based surveillance of sick people and deaths.\nC_LI

epidemiology↗

bioRxiv2019

Google searches accurately forecast RSV hospitalizations

BackgroundHospitalization of children with respiratory syncytial virus (RSV) is common and costly. Traditional sources of hospitalization data, useful for public health decision-makers and physicians to make decisions, are themselves costly to acquire and are subject to delays from gathering to publication. Here we use Google searches for RSV as a proxy for RSV hospitalizations.\n\nMethodsSearches for \"RSV\" and numbers of RSV hospitalizations in WA, MD, FL, and CT were examined from 2004-2018. Running correlation coefficients and phase angles between search and hospitalizations were calculated. Various machine learning models were compared to assess the ability of searches to forecast hospitalizations. Using search data from all 50 US states, we use K-means clustering to identify RSV transmission clusters. We calculate the timing of the optimal timing of RSV prophylaxis initiation as the week beginning the 24-week period covering 95% of all RSV cases.\n\nResultsHigh correlations (> 0.95) and low phase differences were seen between counts of hospitalizations and search volume in WA, MD, FL, and CT. Searching for RSV began in FL and radiated outward and three distinct transmission clusters were identified: the south and northeast, the northwest and Appalachia, and the center of the country. Calculated initiation dates for prophylaxis closely followed those calculated using traditional data sources (correlation = 0.84).\n\nConclusionsThis work validates searches as a proxy for RSV hospitalizations. Search query surveillance of RSV is a rapid and no-cost addition to traditional RSV hospitalization surveillance and may be useful for medical and public health decision-making.

epidemiology↗

bioRxiv2017

Automated collection of pathogen-specific diagnostic data for real-time syndromic epidemiological studies

Health-care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are pathogen-specific. We describe a system, FilmArray(R) Trend, for rapid disease reporting that is syndrome-based but pathogen-specific. Results from a multiplex molecular diagnostic test are sent directly to a cloud database. www.syndromictrends.com presents these data in near real-time. Trend preserves patient privacy by removing or obfuscating patient identifiers. We summarize the respiratory pathogen results, for 20 organisms from 344,000 patient samples acquired as standard of care testing over the last four years from 20 clinical laboratories in the United States. The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks and adenovirus and bacterial pathogens show constant detection over the year. Interestingly, the rate of pathogen co-detections, on average 7.7%, matches predictions based on the relative abundance of organisms present.

epidemiology↗

bioRxiv2016

The risk of sustained sexual transmission of Zika is underestimated

Pathogens can follow more than one transmission route during outbreaks - from needle sharing plus sexual transmission of HIV to small droplet aerosol plus fomite transmission of influenza. Thus, controlling an infectious disease outbreak often requires characterizing the risk associated with multiple mechanisms of transmission. For example, during the Ebola virus outbreak in West Africa, weighing the relative importance of funeral versus health care worker transmission was essential to stopping disease spread [1]. Strategic policy decisions regarding interventions must rely on accurately characterizing risks associated with multiple transmission routes. The ongoing Zika virus outbreak challenges our conventional methodologies for translating case-counts into route-specific transmission risk. Critically, most approaches will fail to accurately estimate the risk of seeing sustained sexual transmission of a pathogen that is primarily vectored by a mosquito - ...

epidemiology↗