Malaria disease transmission models are important tools for controlling and eliminating disease spread. However, a model is only as good as the assumptions about the various variables. Dr. Courtney Murdock, a member of the UGA’s Center for Tropical and Emerging Global Diseases and professor at Cornell University, has been studying how various biological and environmental factors influence mosquito survival. In a study recently published in the Proceedings of the Royal Society B led by graduate student Kerri Miazgowicz, Murdock and her colleagues examined several life traits, such as biting, feeding, and egg production, over the course of the life span of the mosquito Anopheles stephensi in hopes of providing better data for the models.
“Due to a lack of high-quality entomological data in general, researchers are often forced to input data from multiple disease systems to inform models in a given system or use approximations of key model components,” said Murdock.
An. stephensi is the primary mosquito species that transmits malaria in India. While most of the focus on malaria is most often associated with sub-Saharan Africa, it is widespread in the Indian subcontinent and throughout southeast Asia. Several Plasmodium species cause malaria, but P. falciparum is the deadliest of them. It has also shown drug resistance to current treatments. Control of the mosquito population is an important component in malaria control and elimination programs. Researchers need to be able to more accurately predict where mosquito populations will occur as climate changes and current territories become unsuitable living and breeding grounds. Program managers need to be prepared to incorporate more northern regions in their control efforts.
Current models rely on data that are only snapshots in time and often from multiple mosquito species, particularly the African mosquitoes, which are vectors for different malaria species. Miazgowicz, Murdock, and colleagues wanted to determine if the data from a single species of mosquito and parasite, over the course of its entire lifespan, significantly influenced current models in determining disease transmission in hopes of creating more accurate models.
The single most important factor driving current models is temperature. Mosquitoes are cold-blooded animals and therefore rely on their environment to regulate their body temperature. However, temperature is not the only factor influencing life traits. Currently, data are only available as snapshots in time. These incomplete data do not take into account for changes in mosquito behavior and life traits that occur over the course of the mosquito’s life. Murdock and her colleagues have recorded changes in biological function as the mosquito ages. Just as people slow down biologically as they age – metabolism slows, reproduction ability declines, etc. – the same is true for mosquitos. They also found that various traits peak at different times depending on temperature. Importantly they found that temperature and age significantly affected the number of females taking a blood meal (this is the means in which malaria parasites are transmitted to humans) on a given day, average daily egg production, and ultimately survival.
The findings in this study indicated that the addition of An. stephensi data yielded qualitatively different temperature-transmission suitability relationships compared to models that included multiple malaria vectors. With An. stephensi data, the model predicted a broader geographical range of temperature suitability.
“Accounting for these age and species effects in models of transmission potential alters how much of South Asia is predicted to be suitable for malaria relative to models that do not account for these factors,” said Murdock.
These findings can lead to improved malaria transmission models. However, more study outside the laboratory is needed to truly understand the impact mosquito age has on life traits and thermal tolerance.
“This study highlights a critical need for more research in natural settings characterizing the effects of age on mosquito biology to improve predictions of current and future risk,” concluded Murdock.
Models predicting disease transmission are vital tools for long-term planning of malaria reduction efforts, particularly for mitigating impacts of climate change. We compared temperature-dependent malaria transmission models when mosquito life-history traits were estimated from a truncated portion of the lifespan (a common practice) versus traits measured across the full lifespan. We conducted an experiment on adult female Anopheles stephensi, the Asian urban malaria mosquito, to generate daily per capita values for mortality, egg production and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature–trait relationships estimated from truncated data versus observed lifetime values. Incorporating these temperature–trait relationships into an expression governing the thermal suitability of transmission, relative R0(T), resulted in minor differences in the breadth of suitable temperatures for Plasmodium falciparum transmission between the two models constructed from only An. stephensi trait data. However, we found a substantial increase in thermal niche breadth compared with a previously published model consisting of trait data from multiple Anopheles mosquito species. Overall, this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based suitability predictions of transmission.
K. L. Miazgowicz, M. S. Shocket, S. J. Ryan, O. C. Villena, R. J. Hall, J. Owen, T. Adanlawo, K. Balaji, L. R. Johnson, E. A. Mordecai and C. C. Murdock. Proc Biol Sci. 2020 Jul 29;287(1931):20201093. doi: 10.1098/rspb.2020.1093.
The relationship between Plasmodium falciparum gametocyte density and infections in mosquitoes is central to understanding the rates of transmission with important implications for control. Here, we determined whether field relevant variation in environmental temperature could also modulate this relationship. Anopheles stephensi were challenged with three densities of P. falciparum gametocytes spanning a ~10-fold gradient, and housed under diurnal/daily temperature range (“DTR”) of 9°C (+5°C and -4°C) around means of 20, 24, and 28°C. Vector competence was quantified as the proportion of mosquitoes infected with oocysts in the midguts (oocyst rates) or infectious with sporozoites in the salivary glands (sporozoite rates) at peak periods of infection for each temperature to account for the differences in development rates. In addition, oocyst intensities were also recorded from infected midguts and the overall study replicated across three separate parasite cultures and mosquito cohorts. While vector competence was similar at 20 DTR 9°C and 24 DTR 9°C, oocyst and sporozoite rates were also comparable, with evidence, surprisingly, for higher vector competence in mosquitoes challenged with intermediate gametocyte densities. For the same gametocyte densities however, severe reductions in the sporozoite rates was accompanied by a significant decline in overall vector competence at 28 DTR 9°C, with gametocyte density per se showing a positive and linear effect at this temperature. Unlike vector competence, oocyst intensities decreased with increasing temperatures with a predominantly positive and linear association with gametocyte density, especially at 28 DTR 9°C. Oocyst intensities across individual infected midguts suggested temperature-specific differences in mosquito susceptibility/resistance: at 20 DTR 9°C and 24 DTR 9°C, dispersion (aggregation) increased in a density-dependent manner but not at 28 DTR 9°C where the distributions were consistently random. Limitations notwithstanding, our results suggest that variation in temperature could modify seasonal dynamics of infectious reservoirs with implications for the design and deployment of transmission-blocking vaccines/drugs.
Arboviruses infecting people primarily exist in urban transmission cycles involving urban mosquitoes in densely populated tropical regions. For dengue, chikungunya, Zika and yellow fever viruses, sylvatic (forest) transmission cycles also exist in some regions and involve non-human primates and forest-dwelling mosquitoes. Here we review the investigation methods and available data on sylvatic cycles involving non-human primates and dengue, chikungunya, Zika and yellow fever viruses in Africa, dengue viruses in Asia and yellow fever virus in the Americas. We also present current putative data that Mayaro, o’nyong’nyong, Oropouche, Spondweni and Lumbo viruses exist in sylvatic cycles.
The Asian tiger mosquito, Aedes albopictus, transmits several arboviruses of public health importance, including chikungunya and dengue. Since its introduction to the United States in 1985, the species has invaded more than 40 states, including temperate areas not previously at risk of Aedes-transmitted arboviruses. Mathematical models incorporate climatic variables in predictions of site-specific Ae. albopictus abundances to identify human populations at risk of disease. However, these models rely on coarse resolutions of environmental data that may not accurately represent the climatic profile experienced by mosquitoes in the field, particularly in climatically heterogeneous urban areas. In this study, we pair field surveys of larval and adult Ae. albopictus mosquitoes with site-specific microclimate data across a range of land use types to investigate the relationships between microclimate, density of larval habitat, and adult mosquito abundance and determine whether these relationships change across an urban gradient. We find no evidence for a difference in larval habitat density or adult abundance between rural, suburban, and urban land classes. Adult abundance increases with increasing larval habitat density, which itself is dependent on microclimate. Adult abundance is strongly explained by microclimate variables, demonstrating that theoretically derived, laboratory-parameterized relationships in ectotherm physiology apply to the field. Our results support the continued use of temperature-dependent models to predict Ae. albopictus abundance in urban areas.
Courtney Murdock, an assistant professor with a joint appointment in the College of Veterinary Medicine, the Odum School of Ecology and CTEGD, studies the transmission of mosquito-borne diseases to inform predictions about disease patterns and interventions to disrupt transmission.
Where did you earn degrees and what are your current responsibilities at UGA?
I earned my Bachelor of Science degree in biology with a minor in Spanish literature at the University of Michigan, where I also earned my Ph.D. in the School of Natural Resources and the Environment. I was a postdoctoral researcher in the departments of biology and entomology at Pennsylvania State University and am currently an assistant professor with a joint appointment in the department of infectious diseases in the UGA College of Veterinary Medicine and the Odum School of Ecology.
When did you come to UGA and what brought you here?
I began my current position at UGA in 2014. I was excited to join the faculty here due to the growing expertise in infectious diseases across campus, having access to excellent colleagues in the College of Veterinary Medicine and the world-renowned Odum School of Ecology, and the plethora of resources available concerning facilities, expertise and support for graduate students.
What are your favorite courses and why?
My favorite courses that I took as an undergraduate and graduate student, and to teach as a professor, are ecology courses. Ecology is a modern science that is the study of the interactions among organisms and the environment. This field of study provides key insights into how the environment shapes interactions among organisms, their abundances, where they live, and our overall impact. Ecological knowledge is crucial for understanding and mitigating some of the biggest problems we will have to contend with in the future—some of which include global climate change, natural catastrophes, food and water scarcity, the evolution of antibiotic resistance, and emerging infectious diseases.
What are some highlights of your career at UGA?
My research on mosquito-borne diseases has been well-supported by agencies such as the National Institutes of Health and National Science Foundation, with total funding exceeding $1.2 million since 2014. These funds have supported laboratory research, as well as fieldwork in the U.S. and the Caribbean. The results of my research have been published in high-quality scientific journals of international standing, and my research findings have been cited nearly 1,000 times.
I also mentor 17 undergraduate students, one D.V.M. student, five Ph.D. students, and two postdoctoral researchers. All of my mentees gain hands-on experience working in an infectious disease system in the lab or field, as well as exposure to a diversity of host-parasite/pathogen systems and projects that are both basic and applied in nature. My students have a strong record of success, with two NSF Graduate Research Fellowships, four travel awards to attend international conferences to present their work, and two awards for presenting research at local venues.
How do you describe the scope and impact of your research or scholarship to people outside of your field?
I am interested in understanding what drives the transmission of mosquito-borne diseases. The mosquito is the deadliest organism on this planet because of the harmful organisms it transmits to humans, wildlife and domestic animals. Many of these diseases cannot be treated with drugs or prevented with vaccines. Thus, only through an understanding of the transmission process will we be able understand when we are at most risk to contract these diseases, predict how current disease distributions might change in the future, and develop interventions that efficiently disrupt transmission.
How does your research or scholarship inspire your teaching, and vice versa?
For me there is quite a bit of cross-talk between my research knowledge and experiences and my teaching. One important goal as an instructor in the sciences is to impart a solid understanding of the scientific process. Many students who take my courses do not necessarily want a career in science. I believe that to be informed citizens, however, they need to be able to think critically about science and its contributions to society. The best way I have found outside of lab sections to impart this knowledge is from drawing on my own research experiences. I also have found that my teaching informs the direction of my research program because it encourages me to think about my research from the perspective of foundational concepts in ecology.
What do you hope students gain from their classroom experience with you?
In general, the learning objectives for my courses include understanding the conceptual foundations of ecology, becoming comfortable understanding and working with scientific data, being familiar with the scientific method, and being able to engage in discussion and make informed decisions about ecological and environmental issues.
On the less concrete side, I want them to wonder at how amazing the natural world is, be curious about it, understand our part and overall impact, and to be more informed, science-literate citizens.
Describe your ideal student.
Here are some characteristics I value in both undergraduate and graduate students that I work with (this is not ranked in any particular order):
Curiosity—always questioning why and how.
Self-starter—only you can advocate for your interests and education.
Life learner—there is no rubric for life; college and graduate school is the perfect place to begin learning how to teach yourself the material you need to know to pass the test, complete course objectives, fulfill job expectations, answer your own questions, etc.
Positive—this shapes everything, your outlook on life and work, general happiness, interactions with co-workers.
Hardworking – willing to do what is needed to get the task at hand done.
Creative – ability to think outside of the box, willingness to explore and adopt concepts from other fields in order to innovate or solve existing problems.
Team member – working effectively with people with different backgrounds, knowledge, working styles and personalities is a life skill that is beneficial across a diversity of situations and careers.
Fearless – failure is an opportunity to learn and grow.
Responsible – this goes beyond just being reliable and detail oriented. It involves taking ownership over success and failure as well as both positive and negative interactions with others.
Human – have outside interests, be respectful to others, empathize with others.
Favorite place to be/thing to near campus is…
… eating lunch at Cali N Tito’s with colleagues or members of my lab.
Beyond the UGA campus, I like to…
In addition to being a scientist and a professor, I am a mother of two kids, a wife, a daughter, a sister, and a friend. I spend as much time as I can manage with my family and friends outside of work. This involves simple things like going swimming with the kids at the YMCA, going to the local library, going to museums or Lego Land in Atlanta, playing at local parks when the weather is nice, hiking at Fort Yargo State Park or Sandy Creek Nature Center, and occasionally camping in the mountains of Georgia. We also spend a lot of our vacation visiting family in Chicago, Illinois, and Traverse City, Michigan.
Favorite book/movie (and why)?
Favorite nonfiction: “Devil in the White City.” I grew up in the suburbs of Chicago, so it was really insightful and fun to read about how much of the city and world was shaped by the World Fair of 1893. There is also a side story involving a serial killer, which is totally gripping.
Favorite fiction: The “Outlander” series by Diana Gabaldon. These novels are historical fiction, mixed with fantasy and a pinch of romance. The characters are well developed, complex, and the history well researched, so is a perfect storm for losing oneself completely.
The one UGA experience I will always remember will be…
Every year my lab picks a themed costume and dresses up for Halloween. To me this is special, as it is an opportunity for our group to do something fun, wacky and together. Current pictures are on our website: https://www.themurdocklab.com/people.
Is there anything else you’d like to add?
I was an NCAA Division 1 scholar-athlete. I walked on to the University of Michigan softball team as a freshman during my undergraduate career. While I never started, I learned a lot of life skills from this experience that translate to my perspective on life, challenges, teamwork and leadership. I feel like there are stereotypes associated with student-athletes that are oftentimes unwarranted concerning their scholarship, and we should be mindful of this in our interactions with student-athletes in the classroom. I feel that they bring a lot of underappreciated assets to the table.
Background: The malaria Eradication Research Agenda (malERA) has identified human-to-mosquito transmission of Plasmodium falciparum as a major target for eradication. The cornerstone for identifying and evaluating transmission in the laboratory is standard membrane feeding assays (SMFAs) where mature gametocytes of P. falciparum generated in vitro are offered to mosquitoes as part of a blood-meal. However, propagation of “infectious” gametocytes requires 10–12 days with considerable physico-chemical demands imposed on host RBCs and thus, “fresh” RBCs that are ≤ 1-week old post-collection are generally recommended. However, in addition to the costs, physico-chemical characteristics unique to RBC donors may confound reproducibility and interpretation of SMFAs. Cryogenic storage of RBCs (“cryo-preserved RBCs”) is accepted by European and US FDAs as an alternative to refrigeration (4 °C) for preserving RBC “quality” and while cryo-preserved RBCs have been used for in vitro cultures of other Plasmodia and the asexual stages of P. falciparum, none of the studies required RBCs to support parasite development for > 4 days.
Results: Using the standard laboratory strain, P. falciparum NF54, 11 SMFAs were performed with RBCs from four separate donors to demonstrate that RBCs cryo-preserved in the gaseous phase of liquid nitrogen (− 196 °C) supported gametocytogenesis in vitro and subsequent gametogenesis in Anopheles stephensimosquitoes. Overall levels of sporogony in the mosquito, as measured by oocyst and sporozoite prevalence, as well as oocyst burden, from each of the four donors thawed after varying intervals of cryopreservation (1, 4, 8, and 12 weeks) were comparable to using ≤ 1-week old refrigerated RBCs. Lastly, the potential for cryo-preserved RBCs to serve as a suitable alternative substrate is demonstrated for a Cambodian isolate of P. falciparum across two independent SMFAs.
Conclusions: Basic guidelines are presented for integrating cryo-preserved RBCs into an existing laboratory/insectary framework for P. falciparum SMFAs with significant potential for reducing running costs while achieving greater reliability. Lastly, scenarios are discussed where cryo-preserved RBCs may be especially useful in enhancing the understanding and/or providing novel insights into the patterns and processes underlying human-to-mosquito transmission.
Background: Yellow fever virus is a mosquito-borne flavivirus that persists in an enzoonotic cycle in non-human primates (NHPs) in Brazil, causing disease in humans through spillover events. Yellow fever (YF) re-emerged in the early 2000s, spreading from the Amazon River basin towards the previously considered low-risk, southeastern region of the country. Previous methods mapping YF spillover risk do not incorporate the temporal dynamics and ecological context of the disease, and are therefore unable to predict seasonality in spatial risk across Brazil. We present the results of a bagged logistic regression predicting the propensity for YF spillover per municipality (administrative sub-district) in Brazil from environmental and demographic covariates aggregated by month. Ecological context was incorporated by creating National and Regional models of spillover dynamics, where the Regional model consisted of two separate models determined by the regions’ NHP reservoir species richness (high vs low).
Results: Of the 5560 municipalities, 82 reported YF cases from 2001 to 2013. Model accuracy was high for the National and low reservoir richness (LRR) models (AUC = 0.80), while the high reservoir richness (HRR) model accuracy was lower (AUC = 0.63). The National model predicted consistently high spillover risk in the Amazon, while the Regional model predicted strong seasonality in spillover risk. Within the Regional model, seasonality of spillover risk in the HRR region was asynchronous to the LRR region. However, the observed seasonality of spillover risk in the LRR Regional model mirrored the national model predictions.
Conclusions: The predicted risk of YF spillover varies with space and time. Seasonal trends differ between regions indicating, at times, spillover risk can be higher in the urban coastal regions than the Amazon River basin which is counterintuitive based on current YF risk maps. Understanding the spatio-temporal patterns of YF spillover risk could better inform allocation of public health services.
Zika was once thought of as a problem contained to tropical and sub-tropical parts of the world. Today we know better – with 3.9 billion people in 120 countries around the globe at risk of contracting some type of arboviral disease – Zika and related diseases like dengue and chikungunya are spreading, opening up the threat to more and more of the world’s population as our climate changes.
In a new study recently published in the Proceedings of the Royal Society B, researchers from the University of Georgia, Stanford University, Harvard University, and the University of Florida have found that temperature is a driving factor in the transmission of the Zika virus. The team, led by Dr. Courtney Murdock, an assistant professor of infectious disease and ecology at the University of Georgia College of Veterinary Medicine and Odum School of Ecology, and Blanka Tesla, a graduate student at UGA, measured the effect of temperature on the probability of transmission from an infectious mosquito to a human, how quickly the virus spreads throughout the mosquito’s body, allowing it to get into their saliva and become infectious, and areas in the world most suitable for Zika transmission.
They discovered that temperature had a strong effect on mosquito infection and survival traits, and that the least optimal temperatures for transmission were the highest and the lowest temperatures they tested. Thus, as temperatures edge upwards due to climate change, increasing urbanization, or with time of the year, the environmental suitability for Zika transmission should increase. This would result in an expansion of Zika further north and into longer seasons. In contrast, areas that are already permissive or near the thermal optimum for Zika transmission are predicted to experience a decrease in overall environmental suitability.
They then compared the Zika transmission model to one used to predict dengue. Here they discovered that Zika is transmitted more readily at warmer temperatures than dengue virus, which means that current estimates on the global environmental suitability for Zika transmission using dengue as a surrogate are vastly over-predicting its possible range.
“While there are certainly other factors that need to be examined when it comes to the transmission of Zika, this study established that temperature plays a very important role,” said Courtney Murdock assistant professor of infectious disease and ecology at the UGA College of Veterinary Medicine and Odum School of Ecology. “As climate change continues to evolve world-wide, this shows us that we need to keep a watchful eye on how rising temperatures impact the spread of these types of disease.”
The full article was published in the Proceedings of the Royal Society B on August 15, 2018.
Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. Like most viral infections, ZIKV viremia varies over several orders of magnitude, with unknown consequences for transmission. To determine the effect of viral concentration on ZIKV transmission risk, we exposed field-derived Ae. aegypti mosquitoes to four doses (103, 104, 105, 106 PFU/mL) representative of potential variation in the field. We demonstrate that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected, and consequently disseminating virus and becoming infectious. Additionally, we observed significant interactions between dose and days post-infection on dissemination and overall transmission efficiency, suggesting that variation in ZIKV dose affects the rates of midgut escape and salivary gland invasion. We did not find significant effects of dose on mosquito mortality. We also demonstrate that detecting virus using RT-qPCR approaches rather than plaque assays potentially over-estimates key transmission parameters, including the time at which mosquitoes become infectious and viral burden. Finally, using these data to parameterize an R0 model, we showed that increasing viremia from 104 to 106 PFU/mL increased relative R0 3.8-fold, demonstrating that variation in viremia substantially affects transmission risk.