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One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant

One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant pathogens. Not only is this strategy costly and time consuming, it is also unsustainable. To contend with this problem, many multi-drug treatment strategies are being explored. Previous studies have shown that resistance to some drug combinations is not possible, for example, resistance to a common antifungal drug, fluconazole, seems impossible in the presence of radicicol. We believe that in order to understand the viability of multi-drug strategies in combating drug resistance, we must understand the full spectrum of resistance mutations that an organism can develop, not just the most common ones. It is possible that rare mutations exist that are resistant to both drugs. Knowing the frequency of such mutations is important for making predictions about how problematic they will be when multi-drug strategies are used to treat human disease. This experiment aims to expand on previous research on the evolution of drug resistance in S. cerevisiae by using molecular barcodes to track ~100,000 evolving lineages simultaneously. The barcoded cells were evolved with serial transfers for seven weeks (200 generations) in three concentrations of the antifungal Fluconazole, three concentrations of the Hsp90 inhibitor Radicicol, and in four combinations of Fluconazole and Radicicol. Sequencing data was used to track barcode frequencies over the course of the evolution, allowing us to observe resistant lineages as they rise and quantify differences in resistance evolution across the different conditions. We were able to successfully observe over 100,000 replicates simultaneously, revealing many adaptive lineages in all conditions. Our results also show clear differences across drug concentrations and combinations, with the highest drug concentrations exhibiting distinct behaviors.

ContributorsApodaca, Samuel (Author) / Geiler-Samerotte, Kerry (Thesis director) / Schmidlin, Kara (Committee member) / Huijben, Silvie (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in

Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in about 15% of parasites that develop ookinetes in the mosquito abdomen, sporozoites never develop in the salivary glands, indicating that passage across the midgut lumen is a significant barrier in parasite development (Gamage-Mendis et al., 1993). We aim to investigate a possible correlation between passage through the midgut lumen and drug-resistance trends in Plasmodium falciparum parasites. This study contains a total of 1024 Anopheles mosquitoes: 187 Anopheles gambiae and 837 Anopheles funestus samples collected in high malaria transmission areas of Mozambique between March and June of 2016. Sanger sequencing will be used to determine the prevalence of known resistance alleles for anti-malarial drugs: chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1) gene, dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr). We compare prevalence of resistance between abdomen and head/thorax in order to determine whether drug resistant parasites are disproportionately hindered during their passage through the midgut lumen. A statistically significant difference between resistance alleles in the two studied body sections supports the efficacy of new anti-malarial gene surveillance strategies in areas of high malaria transmission.

ContributorsPhillips, Keeley Isabella (Author) / Huijben, Silvie (Thesis director) / Gile, Gillian (Committee member) / Young, Steven (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost. Resistance to insecticides has the potential to increase vector-borne disease

Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost. Resistance to insecticides has the potential to increase vector-borne disease rates. Aedes aegypti is an invasive mosquito species in Arizona and is a known potential vector for a variety of infectious diseases including dengue, chikungunya, Zika, and yellow fever. In contrast to many other mosquito species Ae. aegypti mosquito eggs can undergo quiescence, an active state of dormancy, over long periods of time. Variation in quiescent periods correlates to climatic rainfall alterations and can ultimately influence hatching and mating between multiple generations. I have studied the effect of quiescence on larvicide (i.e., temephos) susceptibility using mosquito eggs collected from a susceptible lab strain and stored under optimal temperature and humidity conditions. After undergoing various quiescent periods (3, 7, 14, 28, 84, and 182 days), the experimental eggs as well as 7-day quiescent control eggs were hatched and reared to 3rd instar larvae. Temephos susceptibility was tested using the WHO bioassay procedure at lethal concentration (LC) 20, LC50, LC80, diagnostic dose (twice LC99), plus an untreated control. Each concentration dose was replicated four times with 20 larvae each. The 3-day experimental group was excluded from analysis because the mortality was significantly lower than the 7-day for both the experimental and control groups. The 3 day experimental eggs displayed decreased mortality which did not align with the hypothesis, as the quiescence period elongates under optimal conditions, susceptibility to insecticides decreases, and this could have likely resulted from unintentional selection for increased fitness and faster developing eggs because the larvae that developed to 3rd instar first were those used for larvicide testing. ANOVA testing demonstrates variability in the LC80 experimental group which suggests the need for further investigation into high dose temephos concentrations. For the experimental LC20 linear regression, there were significant differences in mortality. The results indicate mortality gradually decreases when the quiescence period elongates, therefore there are significant differences in insecticide susceptibility when quiescence is 182 days (or longer), compared to when quiescence is 7 days. Further investigation into field mosquito’s genetic diversity, insecticide resistance profile, and environmental conditions should be considered.

ContributorsKayce, Brenna Jean (Author) / Huijben, Silvie (Thesis director) / Paaijmans, Krijn (Committee member) / Jensen, Brook (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

Vector-borne diseases, such as Zika, chikungunya, dengue, and yellow fever, cause a significant portion of the global infectious disease problem, thereby representing an enormous public health threat worldwide. The threat has become more concerning as Aedes aegypti, who serve as primary vectors for these infectious diseases, continue to thrive in

Vector-borne diseases, such as Zika, chikungunya, dengue, and yellow fever, cause a significant portion of the global infectious disease problem, thereby representing an enormous public health threat worldwide. The threat has become more concerning as Aedes aegypti, who serve as primary vectors for these infectious diseases, continue to thrive in highly populated, urban environments. To solve this problem, insecticides have commonly been used, but this has brought forward additional issues. The overreliance on insecticides has resulted in insecticide resistant individuals emerging within once susceptible populations. Insecticide resistance in Ae. aegypti is a worldwide problem because it compromises the ability to control Ae. aegypti populations, thus increasing the spread of vector-borne diseases. With pyrethroids being commonly used worldwide, the mechanisms behind the knock-down resistance (kdr) are essential to investigate. Investigating the fitness of kdr resistant Ae. aegypti is essential in order to better understand their ability to reproduce and survive in a natural environment. Kdr resistant mutations are known to come with fitness costs: a highly energetic cost or a significant disadvantage that diminishes an aspect of the individual’s fitness. Although it is known that resistance comes with a cost, many research gaps remain. Still, it is unknown whether resistant genotypes differ in larval development times, immature survival, and adult qualities (body weight and wing length). As such, this study observed the impact of the larval development of Ae. aegypti genotypes with varying resistance at loci 1016 and 1534 of the voltage gated sodium channels. The 1016 kdr mutation results in a valine to isoleucine amino acid substitution at position 1016 (V1016I), and the 1534 kdr mutation results in a phenylalanine to cysteine amino acid substitution at position 1534 (F1534C). All strains included in this study were homozygous resistant for the 1534 mutation, while genotype varied at the 1016 locus. Mosquito strains were named after their genotype and are VVCC, VICC, and IICC. Mosquito larvae of each genotype were placed at three temperatures (22℃, 27℃, 32℃) and time to pupation, emergence, immature mortality, sex ratio, dry weight, and wing length was measured. In congruence with previous data, larval pupation and emergence occurred at a faster rate in hotter temperatures (32℃) than in colder temperatures (22℃) for all genotypes. Furthermore, the observed data shows that male mosquitos generally emerged before female mosquitos, regardless of temperature or strain. Interestingly, there were no significant differences between different genotypes in any of the fitness parameters, although the times to pupation suggest a potential trend of increased developmental time with increased resistivity. Ultimately, this data brings important implications to come up with better solutions in vector control programs in order to decrease the likelihood of adult mosquitoes becoming infected and delivering more infective bites. The study also brings light into on where future studies should take place, such as immature competition experiments, and reproductive fitness parameters in order to provide a more complete picture of the life history traits of Ae. aegypti with kdr mutations.

ContributorsSpurlin, Chance (Author) / Huijben, Silvie (Thesis director) / Paaijmans, Krijn (Committee member) / Jensen, Brook (Committee member) / Kalmouni, Joshua (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
Description

Aedes aegypti are vectors for common arthropod-borne-diseases (arboviruses) such as Zika, yellow fever, dengue, and chikungunya, which are of significant public health concern. The management of vectors is critical to mitigating the incidence, reemergence, and expansion of these diseases. Vector control has been complicated by the emergence of insecticide resistance

Aedes aegypti are vectors for common arthropod-borne-diseases (arboviruses) such as Zika, yellow fever, dengue, and chikungunya, which are of significant public health concern. The management of vectors is critical to mitigating the incidence, reemergence, and expansion of these diseases. Vector control has been complicated by the emergence of insecticide resistance within vectors, which threatens the effectiveness of control efforts. Furthermore, vector management is also complicated by the interaction between insecticide susceptibility and abiotic factors, such as temperature. While it is well-documented that environmental factors affect insecticide susceptibility, it is poorly understood how insecticide resistant vectors with different genetic backgrounds respond to insecticides at different temperatures. This study aims to establish the relationship between deltamethrin susceptibility at varying temperatures across Ae. aegypti lines that differ in their susceptibility due to knockdown resistance (kdr) mechanism. This was done through exposures using the “WHO tube test method” using simulated climate environments (22°C, 27 °C, and 32 °C) on mosquitoes of varying resistance at 1016 and homozygous resistance at 1534. This experiment is still ongoing. This study found that IICC was the most resistant genotype, VVCC the least resistant, and VICC and intermediate. There was found to be no statistically significant relationship between temperature and insecticide susceptibility across kdr genotypes.

ContributorsAin, Joshua (Author) / Paaijmans, Krijn (Thesis director) / Huijben, Silvie (Committee member) / Jensen, Brook (Committee member) / Kalmouni, Joshua (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05
Description

The majority of the public is not aware that common objects in their backyard can be mosquito breeding sites, thus leading to an increase in mosquitoes and mosquito-borne diseases affecting humans and animals during the peak seasons. An engaging app that instructs people of all ages how to identify, prevent,

The majority of the public is not aware that common objects in their backyard can be mosquito breeding sites, thus leading to an increase in mosquitoes and mosquito-borne diseases affecting humans and animals during the peak seasons. An engaging app that instructs people of all ages how to identify, prevent, and eliminate breeding sites may be of use in increasing positive behavioral changes in people, and therefore reducing available breeding sites for mosquitoes. The Embodied Games Lab in Psychology at Arizona State University created an educational game phone app using machine learning to teach students how to identify and eliminate mosquito breeding sites. Skeeter Breeder is an interactive, educational game that teaches participants about potential mosquito breeding sites and how to eliminate them from the immediate environment as documented by smartphone imagery. Currently, there is no educational game phone app that uses machine learning to teach this topic. This Thesis describes a pilot study focused on educating about common mosquito breeding sites and increasing the knowledge of 5th graders on the topic through an agentic (by taking their own pictures), engaging (game-like platform with rewards), and interactive (receiving immediate feedback on pictures) game developed from scratch at ASU.

ContributorsBharti, Aarushi (Author) / Johnson-Glenberg, Mina (Thesis director) / Huijben, Silvie (Committee member) / Barrett, The Honors College (Contributor) / Tech Entrepreneurship & Mgmt (Contributor) / Computing and Informatics Program (Contributor)
Created2023-05
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Description
Despite its well-documented preference for much more humid climates, the yellow fever mosquito, or Aedes aegypti, has inhabited Arizona since 1951. Their presence is of great concern as they can transmit many deadly diseases, including yellow fever, chikungunya, Zika, and dengue fever, putting the residents of the Phoenix Metropolitan Area

Despite its well-documented preference for much more humid climates, the yellow fever mosquito, or Aedes aegypti, has inhabited Arizona since 1951. Their presence is of great concern as they can transmit many deadly diseases, including yellow fever, chikungunya, Zika, and dengue fever, putting the residents of the Phoenix Metropolitan Area at risk. Maricopa County Vector Control has made an extensive effort to reduce this risk mainly through the act of fogging insecticides during the night in areas where mosquito numbers exceed a threshold. However, given the well-known temperature-toxicity relationships in insect species, fogging at night may be less or more effective —depending on the relationship— due to the colder temperatures at these times. Additionally, insecticide resistance testing has always been performed at temperatures not usually experienced during fogging, adding to the uncertainty on how useful those test outcomes are. This study took the first steps in determining the effects of temperature on the toxicity of a commonly used insecticide, deltamethrin, on Aedes aegypti by developing a dose response curve on a lab strain at a standard lab temperature of 25°C by performing a CDC bottle bioassay. The diagnostic dose was found to be 50 μg/mL and the lethal dose, 50% (LD50, the dose required to kill half of the test mosquitoes) was found to be 9 μg/mL. Future testing would need to be completed to compare the deltamethrin dose response curve developed in this study with deltamethrin dose response curves at various different temperatures.
ContributorsEl Sheikha, Mariam D (Co-author) / El Sheikha, Mariam (Co-author) / Paaijmans, Krijn (Thesis director) / Huijben, Silvie (Committee member) / Kalmouni, Joshua (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
The non-native mosquito Aedes aegypti has become a common nuisance in Maricopa county. Associated with human settlement, Ae. aegypti is known to reproduce in standing water sources both indoors and outdoors, within vessels such as tires, flowerpots, and neglected swimming pools (Jansen & Beebe, 2010). Ae. aegypti and the related

The non-native mosquito Aedes aegypti has become a common nuisance in Maricopa county. Associated with human settlement, Ae. aegypti is known to reproduce in standing water sources both indoors and outdoors, within vessels such as tires, flowerpots, and neglected swimming pools (Jansen & Beebe, 2010). Ae. aegypti and the related Ae. albopictus are the primary vectors of the arboviral diseases chikungunya, Zika, yellow fever and dengue. Ae. aegypti tends to blood feed multiple times per gonotrophic cycle (cycle of feeding and egg laying) which, alongside a preference for human blood and close association with human habitation, contributes to an increased risk of Ae. aegypti borne virus transmission (Scott & Takken, 2012). Between 2010-2017, 153 travel-associated cases of dengue were reported in the whole of Arizona (Rivera et al., 2020); while there have been no documented locally transmitted cases of Aedes borne diseases in Maricopa county, there are no apparent reasons why local transmission can’t occur in the future via local Aedes aegypti mosquitoes infected after feeding from travelling viremic hosts. Incidents of local dengue transmission in New York (Rivera et al., 2020) and Barcelona (European Center for Disease Control [ECDC], 2019) suggest that outbreaks of Aedes borne arbovirus’ can occur in regions more temperate than the current endemic range of Aedes borne diseases. Further, while the fact that Ae. aegypti eggs have a high mortality rate when exposed to cold temperatures limits the ability for Ae aegypti to establish stable breeding populations in temperate climates (Thomas, Obermayr, Fischer, Kreyling, & Beierkuhnlein, 2012), global increases in temperature will expand the possible ranges of Ae aegypti and Aedes borne diseases.
ContributorsHon, Ruiheng (Author) / Paaijmans, Krijn (Thesis director) / Bond, Angela (Committee member) / Angilletta, Michael (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
After giving birth, protections are essential to provide a mother with the time and ability to support her new child. There are several considerations for policy makers when they establish a maternity leave policy that best facilitates bonding, wellbeing, and the health of the mother-infant dyad. Within Switzerland, maternity leave

After giving birth, protections are essential to provide a mother with the time and ability to support her new child. There are several considerations for policy makers when they establish a maternity leave policy that best facilitates bonding, wellbeing, and the health of the mother-infant dyad. Within Switzerland, maternity leave policy permits fourteen-weeks of paid leave, including an optional two week unpaid extension. To understand how Swiss women are experiencing the current maternity leave policy, a scholarly database search was conducted and six interviews were held with stakeholders in Switzerland. Several themes emerged through the interviews, particularly, the mother-infant dyad, and the mental & physical health of the new mother. Stakeholders found the current leave policy within Switzerland may be sufficient, on average, to support women’s physical healing post-birth. However, it may act as a barrier for mental health interventions, and achieving breastfeeding goals which benefit both mother and child. Several stakeholders suggested lengthening maternity leave to remove these barriers. This study emphasizes the need for policy makers to consider the complex impacts of maternity leave policy on not only the health of the child, but also the mother.
ContributorsClifford, Sarah Elizabeth (Author) / Hinde, Katie (Thesis director) / Bond, Angela (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Malaria is a deadly, infectious, parasitic disease which is caused by Plasmodium parasites and transmitted between humans via the bite of adult female Anopheles mosquitoes. The primary insecticide-based interventions used to control malaria are indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs). Larvicides are another insecticide-based intervention which is

Malaria is a deadly, infectious, parasitic disease which is caused by Plasmodium parasites and transmitted between humans via the bite of adult female Anopheles mosquitoes. The primary insecticide-based interventions used to control malaria are indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs). Larvicides are another insecticide-based intervention which is less commonly used. In this study, a mathematical model for malaria transmission dynamics in an endemic region which incorporates the use of IRS, LLINS, and larvicides is presented. The model is rigorously analyzed to gain insight into the asymptotic stability of the disease-free equilibrium. Simulations of the model show that individual insecticide-based interventions will not realistically control malaria in regions with high endemicity, but an integrated vector management strategy involving the use of multiple interventions could lead to the effective control of the disease. This study suggests that the use of larvicides alongside IRS and LLINs in endemic regions may be more effective than using only IRS and LLINs.
ContributorsJameson, Leah (Author) / Gumel, Abba (Thesis director) / Huijben, Silvie (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Civic & Economic Thought and Leadership (Contributor)
Created2022-05