Targeting the Parasite within the Vector: 

Exploring Novel Approaches to Prevent 

Transmission of Vector-Borne Diseases 

A Virtual Workshop Sponsored by the 

Division of Microbiology and Infectious Diseases 

National Institute of Allergy and Infectious Diseases 

National Institutes of Health 

July 20–21, 2021 

Meeting Report 
 

 

 

 

 

 

 

 

 

 

Table of Contents 

EXECUTIVE SUMMARY.............................................................................................................................. 3 

MEETING SUMMARY ................................................................................................................................. 4 

Introduction and Purpose..................................................................................................................... 4 

Session 1: State of the Science for Parasite/Vector Systems................................................................ 5 

Session 2: Approaches to Target the Parasite within the Vector....................................................... 12 

Session 3: Tools to Accelerate Research............................................................................................ 17 

Reports from the Breakout Groups..................................................................................................... 22 

APPENDIX A: PARTICIPANTS LIST .......................................................................................................... 28 

APPENDIX B: RESOURCES AND BACKGROUND MATERIALS .................................................................. 33 

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Executive Summary 

Organizers from the Division of Microbiology and Infectious Diseases (DMID) of the National 

Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health brought 

together experts in vector biology, parasitology, and related areas to discuss approaches to 

interrupt parasite development within the arthropod host and prevent transmission of human 

vector-borne diseases. In accordance with NIAID’s goals, the virtual workshop promoted 

communication and multidisciplinary collaboration among researchers, highlighted existing and 

needed resources, and sparked ideas about accelerating research. Lee Hall, Chief of DMID’s 

Parasitology and International Programs Branch, opened the workshop and outlined his vision 

that the meeting would lay the foundation for the development of interventions and ultimately 

accelerate the needed public health mechanisms to address the burden of vector-borne disease. 

On day one of the workshop, participants heard oral presentations on the state of the science for 

four parasite/vector systems: trypanosome/tsetse fly, trypanosome/triatomine bug, 

Plasmodium/mosquito, and Leishmania/sand fly. Additional presentations covered various 

approaches to targeting the parasite within the vector and tools available to accelerate research. 

On day two, participants met in breakout sessions to identify limitations, opportunities, 

mechanisms for enhancing target discovery, and research priorities for the four parasite/vector 

systems discussed on day one, plus tick-borne diseases. 

The breakout sessions yielded numerous suggestions for advancing research. Four cross-cutting 

points emerged: 

• Core facilities are needed to generate reagents and organisms (pathogens and 

vectors) to increase consistency and reproducibility. 

• The field of vector/pathogen interactions needs new ideas from a broader 

investigator pool with different perspectives. A web-based platform for linking 

investigators across research specialties might be a good start to enable 

multidisciplinary collaborations and facilitate the exchange of ideas. 

• Better information and data management and sharing are needed across research 

fields. 

Prior to the workshop, a communication platform was established to encourage participants to 

exchange ideas, information, and resources. The tool will be maintained to encourage continued 

collaboration among experts from the many different disciplines involved in targeting the 

pathogen within the arthropod vector. 

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Meeting Summary 

Introduction and Purpose 

Organizers from the Division of Microbiology and Infectious Diseases (DMID) of the National 

Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) 

brought together experts in vector biology, parasitology, and related areas to discuss approaches 

to interrupt parasite development within the arthropod host and prevent transmission of human 

vector-borne diseases. The goals of the workshop were as follows: 

• Promote communication and collaboration among researchers 

• Highlight existing resources and tools available 

• Identify additional resources and tools needed 

• Spark ideas to accelerate research and ultimately prevent transmission of vector-borne 

pathogens 

Day one of the workshop consisted of oral presentations on the state of the science for four 

parasite/vector systems: trypanosome/tsetse fly, trypanosome/triatomine bug, 

Plasmodium/mosquito, and Leishmania/sand fly. Additional presentations covered various 

approaches to targeting the parasite within the vector and tools available to accelerate research. 

On day two, participants met in breakout sessions to identify limitations, opportunities, 

mechanisms for enhancing target discovery, and research priorities for the four parasite/vector 

dyads discussed on day one, plus ticks and tick-borne diseases (See Figure 1). 

Figure 1: Workshop Organization 

The list of participants appears in Appendix A. Resources and background materials can be 

found in Appendix B. A list of selected key publications can be found in Appendix C. 

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Remarks from Lee Hall, Chief, Parasitology and International Programs Branch, DMID, 

NIAID 

Dr. Hall noted that according to the World Health Organization, vector-borne diseases account 

for 17 percent of all infectious diseases and cause more than 700,000 deaths annually, posing a 

substantial burden on society. More effective interventions could have a significant impact on 

morbidity and mortality. For many of these diseases, new interventions and approaches are 

needed. 

This workshop offered an opportunity to address the perception of vectors as “flying syringes.” 

Researchers in the field recognize that vectors are not just passive reservoirs or transporters but 

rather are crucial sites for pathogen development and replication. The complex processes 

involved in pathogen development offer many potential targets for intervention. Dr. Hall hoped 

that the field would capitalize on recent advances in science to devise novel approaches to 

vector-borne disease research, such as gene editing, structure-based design, and influencing the 

microbiome, as well as the use of modern computational tools, systems biology, data science, 

and modeling. He anticipated that this workshop would lay the foundation for the development 

of interventions and ultimately accelerate the needed public health mechanisms to address the 

burden of vector-borne disease. 

Dr. Hall encouraged participants to take advantage of the workshop to engage with peers, seek 

out collaborations, and generate new insights. 

Session 1: State of the Science for Parasite/Vector Systems 

Each speaker gave a brief presentation (either prerecorded or live) on interactions, focusing 

either on the role of the vector or the parasite. Following presentations, participants posed 

questions for discussion. All questions and responses are combined in this summary. 

Trypanosome/Tsetse Fly Interactions 

Vector Speaker: Serap Aksoy, Yale University 

Diseases transmitted by tsetse flies cause significant harm in animals and remain a persistent 

threat for humans. Vector control is highly effective in reducing disease. Parasites undergo three 

major developmental events within the tsetse fly, and, with each event, the efficiency of 

transmission of the parasite decreases. There are barriers to invasion of the tsetse fly at these 

events: the peritrophic matrix; the midgut colonization; and the transmission of infectious 

material into the salivary gland. 

Some genomic data exist for tsetse flies and trypanosomes. Dr. Aksoy called for better curation 

of existing genomics resources, validation of single nucleotide polymorphism discovery data, 

and expanded knowledge about the contributions of microbial partners. She noted that 

paratransgenesis is a fast, effective alternative to transgenesis. Efforts should be made to improve 

maternal transmission efficiency of transgenic symbionts to establish paratransgenic tsetse lines. 

Most functional genomics data come from laboratory lines of tsetse flies, which are limited by 

genetic bottlenecks that result from inbreeding. Investigations with natural populations and field5 
 

 

 

 

 

 

driven colonies are needed. Finally, parasite transgenesis is feasible, and the field should explore 

how to improve the ability of flies to transmit transgenic parasites. 

Parasite Speaker: Christian Tschudi, Yale University 

Dr. Tschudi summarized the history of the science, dating back to the 1903 demonstration of the 

link between trypanosomiasis and tsetse flies and continuing to recent technological advances 

that revolutionized current understanding of the relationship between the arthropod vector and its 

vertebrate host, including genome-wide RNA interference (RNAi), single-cell RNA sequencing 

(scRNA-seq), high-throughput phenotyping, and clustered regularly interspaced short 

palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using these technologies, 

investigators have shed light on trypanosome development within the tsetse fly and the 

expression of key proteins that cause infection in hosts. 

Among the outstanding issues and questions for the field are the following: 

• Genetic exchange takes place, but there are knowledge gaps around the details of the 

second meiotic division, nuclear and kinetoplast DNA exchange, and zygote formation. 

• The mechanics of DNA exchange await elucidation. 

• Does social motility take place during peritrophic matrix crossing or migration to the 

proventriculus? 

• What physical or chemical cues guide the different migration patterns of Trypanosoma 

brucei in the fly? 

• What are the receptors involved in the attachment of epimastigotes to the tsetse salivary 

gland epithelial cells? 

• What signal(s) initiates trypanosome movement and differentiation during the 

developmental cycle in the tsetse? 

Discussion 

It was asked whether the trypanosomes change surface coats while they are in the tsetse gut. Dr. 

Tschudi said the trypanosomes are taken up by the mammalian host, and they carry the variant 

surface glycoprotein coat. As soon as they enter the midgut, they shed the coat and put on a new 

one, which is procyclin, becoming noninfective during that process. Dr. Aksoy said the 

mammalian parasite rapidly changes its coat to the procyclic stage in the vector, typically within 

12 hours. Then the metacyclic parasite, once introduced into the mammalian bite site, also 

undergoes a change to express mammalian variant surface glycoproteins. It takes 36 to 48 hours 

before the process is initiated at the bite site, so there is a short window to interfere with the 

metacyclic parasites at the bite site. Dr. Tschudi added that, from live cell imaging, it appears 

that metacyclic variant surface glycoprotein expression is rapid and only occurs for about 5 hours 

(in an in vitro system), which is surprising. 

There was a discussion about whether any specific motif has been recognized from the genetic 

transcriptions that can identify the mechanism by which RBP6 mutates the expression of genes. 

Dr. Tschudi responded that the targets of RBP6 on messenger RNA have been identified. There 

are about 1,000 of them, across multiple categories, including metabolism, mitochondria, and 

mitogenesis. RBP6 is a master regulator that mainly regulates at the level of transcription and 

translation. 

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Participants also asked about the possibility of developing vaccines against the trypanosome 

pathogen while it is still in the tsetse gut. Dr. Aksoy responded that transmission-blocking 

vaccines have been explored in various systems, and an anti-procyclin vaccine could be pursued, 

although whether such a vaccine can be developed remains an open question. Dr. Aksoy noted 

that vaccine antibodies would be expected to survive, pass the peritrophic matrix barrier, and be 

effective against procyclic infections in the gut. Given new technology, such as paratransgenic 

symbiotic systems, the topic might be worth further discussion, Dr. Aksoy said. 

Trypanosome/Triatomine Bug Interactions 

Vector Speakers: Lori Stevens and Raquel A. Lima-Cordon, University of Vermont 

Innovative genetic analysis techniques combined with liquid chromatography tandem mass 

spectrometry (LC-MS/MS) confirm that the Triatominae abdomen is a rich source of information 

about the vector, parasite, microbiome, and vertebrate blood meal source that can be used to 

develop antiparasitics and transgenics. For example, research demonstrates that the richness and 

community structure of the microbiome vary between infected and uninfected vectors. However, 

more work is needed to investigate the relationships among the transcriptome, microbiome, 

parasite virulence, and vector competence. Furthermore, the ability to identify multiple blood 

meal sources accurately using LC-MS/MS could improve vector control strategies. 

For Chagas disease, questions remain about how much covariation exists within the parasite, 

vector, vertebrate host, and microbiome, but the field lacks enough specimens to achieve 

adequate statistical power in analysis. Researchers developed a method for extracting DNA from 

preserved museum specimens going back to 1935 that yield complete mitochondrial vector 

phylogenies as well as parasite genomics, which could be used to address questions around 

covariation. 

Parasite Speaker: Eric Dumonteil, Tulane University 

From DNA extracted from the abdomen of the triatomine bug, investigators can create a profile 

that includes species identity and population genetics, blood meal sources, parasite genotypes, 

and microbiome factors. Better profiles and genotyping should illuminate what is unique to a 

geographic site that explains differences in prevalence, which could then be targeted for 

intervention. 

A profile of Triatoma dimidiata shows that the bug feeds on multiple vertebrate hosts and 

switches hosts frequently, providing many opportunities to transmit the parasite across multiple 

species. This information can be further mined to reconstruct feeding networks and determine the 

pathways for transmission of disease. These data will inform models that can show the potential 

effects of intervention. For example, reducing infection in chickens or dogs would reduce human 

infection substantially, and reducing infections in both chickens and dogs benefits humans even 

more. Work is underway to expand the concept of manipulating the host community. In addition, 

research is seeking out bacteria that could make triatomine bugs refractory to Trypanosoma cruzi 

infection, an approach suggested 20 years ago but made possible by current tools that allow 

researchers to understand the interactions and opportunities and to break the cycle of infection. 

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Discussion 

A participant noted that Dr. Dumonteil’s feeding profile data could be biased by collection 

biases, because the bugs are mostly collected from human habitats. 

It was asked whether Dr. Stevens’ laboratory has detected triatomine bugs infected with 

Trypanosoma rangeli. A response was given that the parasite had been detected but is more 

commonly found in Rhodnius species. 

There was a discussion on zooprophylaxis as a potentially good approach. The drawback is the 

increase in the local vector population in the area of transmission. The greater the vector 

population, the greater the biting rates and the greater the risk. It was asked how to reduce that 

potential negative effect. Dr. Dumonteil responded that feeding profiles vary a lot according to 

habitat, and bugs from human habitats are indeed biased toward humans and domestic species 

(which are the most important species from an epidemiologic perspective). However, he and his 

colleagues are also investigating sylvatic populations to understand the zoonotic cycles. Dr. 

Dumonteil added that his team is using modeling to assess the conditions under which 

zooprophylaxis might work. 

Malaria Parasite/Mosquito Interactions 

Vector Speaker: Marcelo Jacobs-Lorena, Johns Hopkins University 

The midgut lumen of the mosquito is the best target for interventions to prevent transmission of 

pathogens because it produces the most sporozoites following ingestion of gametocytes. The first 

step toward genetic modification of mosquitoes to secrete compounds that kill the parasite 

(transgenesis) has been accomplished successfully in the laboratory. The use of CRISPR/Cas9 to 

create gene drives has been effective in laboratories but not has not yet been tested in the field. 

Alternatively, paratransgenesis results in creation of bacteria engineered to secrete compounds in 

the gut of the mosquito that kill the parasite. When a mosquito feeds, the number of bacteria in 

the gut increases by 100-fold, so killing the parasite in the gut would ultimately limit the 

transmission of the parasite at the next feeding. Researchers have demonstrated that engineered 

bacteria can spread rapidly through horizontal and vertical transmission in the vector population. 

Transgenesis is more effective than paratransgenesis, but a combination of the two will likely be 

the most successful approach. 

Parasite Speaker: Ashley Vaughan, Seattle Children’s Hospital 

The mosquito bloodmeal is vital for oocyst growth. Neither the parasite nor the mosquito can 

synthesize isoleucine. Optimal oocyst growth requires constant nutritional intake by the 

mosquito. The hormone 20-hydroxyecdysone plays an essential role, with mosquito hormone 

signaling coregulating both egg and parasite development. Knocking down heterodimer 

ecdysone receptor results in fewer oocytes, but they are larger and develop more quickly. Lipids 

are abundant after a blood meal and can be accessed by the developing oocyte as it matures. 

Parasite development requires mitochondrial respiration, heme biosynthesis, and fatty acid 

biosynthesis. 

Dr. Vaughan summarized that Plasmodium falciparum oocyst development requires uptake of 

nutrients associated with the blood meal. Oocysts likely scavenge nutrients from the hemolymph. 

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P. falciparum oocysts require de novo fatty acid synthesis, heme biosynthesis, and mitochondrial 

respiration for sporozoite production. An important question to explore is whether oocysts sense 

nutrient levels and enter a dormant state as needed. Dr. Vaughn noted that in vitro sporozoite 

production is possible but still challenging. In vitro mechanisms are needed to advance research. 

Discussion 

It was asked whether releasing infected mosquitoes into the field could introduce a modified 

bacteria into the environment. Dr. Jacobs-Lorena acknowledged that paratransgenesis and gene 

drives introduce genetically modified organisms into nature, which has social consequences and 

raises regulatory issues. In a major development, Serratia bacteria were isolated from 

mosquitoes in the field that naturally impair parasite development. The Serratia bacteria spread 

through the mosquito without genetic modification, and therefore offer an approach that would 

make paratransgenesis easier to test and, eventually, to implement. It was asked whether 

mosquitoes could develop resistance to the bacteria. Dr. Jacobs-Lorena replied that the Serratia 

bacteria have a symbiotic relationship with the mosquito, with no fitness cost to the mosquito, so 

resistance is unlikely to develop. 

Participants also asked whether any marker exists that could be used to enable paratransgenesis 

in the sand fly. Dr. Jacobs-Lorena said that fluorescence protein genes are introduced into 

bacteria in the laboratory as markers and are easy to follow. In a field trial, fluorescent genes 

could be added to the modified bacteria released to track their progression. 

Participants asked whether paratransgenesis directed against Plasmodium influences the vector 

competence of mosquitoes for other pathogens (e.g., arboviruses). Dr. Jacobs-Lorena did not 

think so, because the effector molecules that are secreted by the bacteria target the parasites 

directly. It could target other parasites, but Anopheline mosquitoes transmit very few other 

pathogens besides Plasmodium. Dr. Jacobs-Lorena did not think paratransgenesis changed the 

physiology of the mosquitoes. If anything, it would impair transmission of other pathogens, not 

facilitate it, he said. 

There was a discussion as to whether the Serratia bacteria colonize the salivary glands of the 

mosquito and could be transmitted to mammals during bites. Dr. Jacobs-Lorena said experiments 

were conducted with a sensitive test to see whether, after feeding on Serratia, mosquitoes could 

release bacteria into the blood meal. The results determined that the bacteria do not go through 

the salivary gland and are not present in the lumen of the salivary gland, so the use of Serratia is 

safe for mammals. 

It was asked whether atovaquone should be added to other antimalarials to protect against 

transmission even if it does not cure people immediately. Dr. Vaughan noted that atovaquone is 

still used in combination with other drugs as a first-line antimalarial defense. It is also effective 

against malaria at the liver stage. 

Participants also asked whether in Fas2 knockouts, sporozoites fail to develop properly in the 

midgut, fail to migrate to the salivary glands, or fail to survive in the salivary glands. Dr. 

Vaughan responded that the P. falciparum sporozoites fail to develop within the oocyst, although 

the oocyst does undergo development. He believes that the fatty acids are essential for the 

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formation of the sporozoite membranes, although he has no direct evidence of this. Interestingly, 

rodent malarias do not require Fas2 during mosquito stage development. 

Leishmania/Sand Fly Interactions 

Parasite Speaker: Steve Beverley, Washington University 

Lipophosphoglycan (LPG) plays a key role in the sand fly vector, and modifying LPG reveals 

some unexpected consequences. Not all species use LPG for binding. Better understanding is 

needed about the relevant parasite/sand fly ligands and receptors. The role of 

proteophosphoglycan in transmission from the fly to the mammalian host and its role in the 

mammalian host should also be elucidated. Research is needed to determine whether endogenous 

microbiota could be engineered to express LPG, which could block binding. Sand flies are not 

widely accessible, so alternatives and model systems would be helpful, such as Drosophila flies 

or cell lines, sand fly cell lines, and midgut organoid cultures. 

The future of research most likely lies in advanced technology that allows investigators to look at 

many genes at once in difficult-to-assay systems. Individual laboratories often do not have the 

resources to take on such big efforts, so the field would benefit from consortia that share 

resources with the community. 

Genetic crossing is key to fly biology and is a fundamental mechanism of genetic diversity. 

Leishmania crossing occurs with sufficient frequency to generate diversity but infrequently 

enough to maintain successful lineages. Crossing could potentially be used for positional cloning 

of complex phenotypes—for example, to identify tropisms in sand flies or human hosts. 

However, this approach requires flies, so alternatives should be explored. One laboratory has had 

some success with in vitro crossing using Leishmania tropica. It is not clear how well the 

approach mimics real crossing, but that might not matter for genetic mapping and could open 

doors in parasite and vector biology research. 

More investigation is needed to understand the impact of Leishmania on the fly, particularly the 

impact on metabolism, the fly’s immune responses, and the role of glycoconjugates. Until 

recently, the creation of sand fly mutants was considered impossible, but it has been achieved via 

CRISPR/Cas9. Maintaining mutant lines in culture is very challenging, especially for sand flies. 

Vector Speaker: Tiago D. Serafim, Division of Intramural Research, NIAID 

More is known about the parasite than the vector, particularly how the vector succeeds as an 

infectant. The sand fly feeds every 5–6 days. With each blood meal, the parasite multiplies in the 

midgut. The sand fly only becomes capable of transmitting infection after the second blood meal. 

The demonstration of a shortened parasite lifecycle that enhances infectivity with every 

successive meal is important not only for understanding Leishmania species in the sand fly but 

also applies to mosquitoes’ transmission of virus, as demonstrated by other investigators. 

Dr. Serafim described research on the role of the microbiota. His mentioned that his laboratory 

found that the sand fly microbiome is important for the sustainability of the parasite within the 

vector. 

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Discussion 

Participants asked how metacyclics in the sand fly gut deal with the metabolites in the blood 

meal, as they are exposed to them multiple times. Dr. Serafim said there are no data to answer 

the question. 

There was a discussion as to whether there is any knowledge about Leishmania parasite stage 

modulation in response to the sand fly midgut microbiota and what is known about the dynamics 

of microbiota composition and diversity in response to consequent blood meals and their 

correlation with parasite stages. Dr. Serafim responded that the parasite does regulate; there is 

selection of some families of sporozoites that the infection progression generates, so the gut loses 

diversity. Which form performs this selection, lowering the amount of bacteria, is not known, 

only that the progression generates it. Regarding metabolites, when the bacteria are extracted and 

the parasite dies, it is possible that the metabolites the bacteria face are toxic to the Leishmania 

parasite, or perhaps something the bacteria generate is essential to the parasite. All of these are 

open questions. It was noted that those bacteria that remain modulate or provide something to the 

parasite to develop, and it would be interesting to address the issue, because interventions could 

use that approach to work against the bacteria. For example, paratransgenesis could be used to 

create bacteria that kill the parasite. 

Participants also asked about: the maximum number of gonotrophic cycles a sand fly can 

complete during its lifetime; how much is known about the difference between leptomonads and 

retroleptomonads; and whether haptomonads ever get transmitted to the vertebrate host or 

whether their role is solely to modify the stomodeal valve and promote transmission of 

metacyclics. It was noted that Serafim’s data suggest that decreasing the lifespan of sand flies in 

the field could reduce the possibility of transmission occurring; she asked what is known about 

the lifespan of sand flies in natural situations. 

In response to questions about the lifecycle of the sand fly in the field, Dr. Serafim said data are 

limited, but there were some experiments in the early 2000s in France involving release and 

recapture of marked flies. Those investigators found three different blood meals in flies that were 

recaptured. The findings suggest that, for at least 21 days, recaptured flies have gone through 

several gonadotrophic cycles. It was noted that other researchers have found that when they 

catch infected flies, the flies had parasites from the proboscis through to the midgut. So, the 

amplification cycle is important to wild, infected sand flies, and the process has not been well 

replicated in the laboratory. 

Participants asked whether the amplification in the number of parasites translated into any 

evidence of increased infectivity of the cells. Dr. Serafim replied that it might be a matter of 

probability. When his laboratory did transmission experiments, researchers found a significant 

increase in the number of lesions, but when the lesions appear—and they are very diminished in 

number among the group that did not take multiple blood meals—the lesion severity was the 

same. Thus, the data so far suggest that the number of lesions does not affect the virulence but 

rather the ability to transmit. Single-cell sequencing has not yet been conducted. 

Participants commented on the need for community-wide collaboration for large-scale 

phenotypic screening. The NIAID-funded Eukaryotic Pathogen, Vector, and Host Informatics 

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Resource (VEuPathDB) supports genome-wide phenotypic data for a variety of assays (e.g., 

fitness, imaging, and curated phenotypes), generated using various approaches (e.g., targeted 

knockouts, transposon mutants, RNAi libraries, and CRISPR knockouts) for a variety of species 

(Aspergillus, Cryptococcus, Neurospora, Plasmodium, and Toxoplasma, with Leishmania under 

discussion). 

Session 2: Approaches to Target the Parasite within the Vector 

Each speaker gave a brief presentation focusing either on the vector or the parasite. Following 

presentations, participants posed questions for discussion directly or via the online chat feature. 

Exposure to Antiparasitics: Ingestion Route 

Parasite Speaker: Paul Bates, Lancaster University 

Efforts to develop antiparasitics have focused on administering a drug to the vector to prevent 

transmission of the parasite to a human host, which poses challenges different from those of 

administering a drug to humans. The success of a transmission-blocking vaccine for the vector 

relies on understanding the immune response of the vector. 

One route of administration for antiparasitics could be ingestion during the blood meal. For 

trypanosomes, the blood meal is the only ingestion route; female mosquitoes and sand flies also 

take sugar meals from plants. The lifecycle of the parasite is critical to the success of the 

ingestion route. Malaria parasites, for example, exit the gut quickly, so the window of 

opportunity is limited, but they could still be targeted in the gut if the antiparasitic agent could 

penetrate through the gut wall. To develop an antiparasitic, researchers would still have to 

identify the precise location to target and take into account how the parasite changes during 

development. 

Drugs or vaccines intended to target the pathogen inside the vector will likely require ingestion 

of the antipathogen compound or antibodies during blood feeding on a human host. Because this 

process would involve the human host being bitten before the drug or vaccine has an effect on 

the pathogen, the drugs or vaccines would likely not have an immediate benefit for the 

individual; rather they would eventually benefit the community by decreasing disease 

transmission. 

There is some proof of principle for transmission-blocking drugs targeting Plasmodium, and 

some research on transmission-blocking vaccines for Plasmodium. Other targets have been 

considered but pose significant challenges. 

Vector Speaker: Marcelo Ramalho-Ortigão, Uniformed Services University of the Health 

Sciences 

The lifecycle of Leishmania in the sand fly offers some potential targets for antiparasitics, 

particularly in the midgut. Dr. Ramalho-Ortigão demonstrated disruption in the peritrophic 

matrix kinetics among female sand flies that were fed anti-PpChit1 (anti-chitinase) and antiPpPer2 (anti-peritrophin). RNAi targeting PpChit1 secreted in the midgut also reduced 

development of Leishmania major in the sand fly. 

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As Dr. Serafim and others have demonstrated, the status of the vector microbiome is critical to 

survival of the parasite. Bacteria in the sand fly larval gut colonize differently depending on the 

pH. Dysregulation (or dysbiosis) of the gut homeostasis leads to bacterial stimulation of the host 

immune response. Therefore, the microbiome could be a platform for paratransgenesis targeting 

either virus or bacteria. There is a great deal of conservancy between genera and species that 

could be exploited for delivering molecules. Technology exists to track the distribution of an 

element added to a sugar meal as it migrates through the sand fly. 

A combined strategy of killing larvae and adults (including bacterial-induced larval killing and 

sugar baits) is more likely to be effective than any single approach. Local communities must be 

part of the decision-making process about vector and parasite control. 

Discussion 

It was asked whether Leishmania infection influences the distribution of different bacteria 

species in the gut. Dr. Ramalho-Ortigão replied that the infection changes the richness and 

diversity, but it is not yet known how it affects areas of the gut. 

Participants also asked how accessible the parasites inside the matrix are to compounds and 

whether there are limitations in molecule size and flux across the matrix. Dr. Ramalho-Ortigão 

said the peritrophic matrix is fairly porous and many compounds will traverse it with ease. For 

example, in an experiment to assess the porosity, 75 kilodalton (kDa) to 100 kDa beads seemed 

to pass easily. 

Exposure to Antiparasitics: Non-Ingestion Route 

Vector Speaker: Flaminia Catteruccia, Harvard University 

Antiparasitics can be applied to mosquito nets, circumventing the emergence of insecticide 

resistance. In low concentrations, atovaquone applied on a surface where a mosquito lands, for 

example, causes the destruction of parasites in the mosquito gut but does not affect mosquito 

survival or reproduction. Thus, there is little selective pressure that could lead to mosquito 

resistance to atovaquone. Research demonstrates that atovaquone exposure kills parasites in 

field- and laboratory-raised mosquitoes, even those highly resistant to insecticides. 

Different drugs are needed to treat the parasites in humans and mosquitoes to mitigate the 

potential development of resistance to drugs delivered by mosquito nets and preserve the 

effectiveness of drugs used in humans. Modeling is needed to assess interventions. Novel 

technology can screen libraries of existing compounds for potential new drugs. New in vitro 

systems are needed to test them. 

Parasite Speaker: Corey Hopkins, University of Nebraska Medical Center 

Using high-throughput screening, Dr. Hopkins and colleagues identified active compounds and 

manipulated them to ensure they were systemically active as mosquito insecticides. The 

following issues should be considered in efforts to develop systemically active compounds: 

• Repurposing certain human drugs may not be effective because compounds active in 

mosquitoes tend to have different fundamental properties (e.g., drugs for mosquitoes 

must be more lipophilic). 

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• The cost of goods is a major concern, as the compound might be used in large quantities 

(such as a spray for nets), which again could limit the utility of expensive human drugs. 

• How the compound will reach the parasite must be considered, particularly whether 

through topical application or ingestion. 

• Investigators should consider how to ensure the parasite receives a sufficient dose of the 

compound; insecticide research might offer some insights. 

• Developing different drugs for humans and mosquitoes that kill the same parasites is a 

valuable strategy to prevent the development of resistance. 

Dr. Hopkins emphasized that more cross-disciplinary collaboration is needed to identify new 

targets. 

Discussion 

Participants noted that Dr. Catteruccia’s proof of principle opens the possibility of delivering 

antiparasitic agents through contact. It was asked whether she had thought about delivery 

systems and how to reach natural populations at scale. Dr. Catteruccia responded that the plan is 

to use bed nets or indoor spraying to deliver the antiparasitic compounds, with mosquitoes 

absorbing them the way they generally absorb insecticides. Therefore, the compounds must 

penetrate the insect cuticle. 

Participants also asked how atovaquone enters the mosquito and how stable atovaquone is on 

surfaces over time. Dr. Catteruccia said atovaquone enters the mosquito via the tarsi, but her 

group is not suggesting using atovaquone on nets because it is used in humans. Stability has not 

yet been measured; such studies would make more sense with candidate antimalarials rather than 

with proof-of-principle compounds. 

Finally, it was asked whether sugar baits would provide a better approach for breaking through 

insecticide resistance. Dr. Catteruccia said her colleagues have tested delivering antimalarials via 

sugar solutions and it works very well, so it may be a viable option. 

Transgenics 

Vector Speaker: Tony James, University of California, Irvine 

Transgenesis in mosquitoes has been achieved using non-homologous recombination, 

homologous recombination (CAS9 and guide RNA [gRNA]), transposons, symbiotic organisms, 

episomes, and viruses. In mosquitoes and parasites, these techniques have been delivered by 

microinjection, electroporation, lipofection, and biolistics. To modulate gene expression profiles, 

investigators have ablated genes; altered transcription product abundance profiles; and altered 

tissue-, sex-, and stage-specificity. Other work has defined functional fragments of gene control 

sequences, introduced exogenous DNA-encoding products, and assessed enhancer traps to 

identify endogenous genes with specific characteristics. 

Dr. James described the mechanisms by which transgenesis works in mosquitoes using class II 

transposable DNA elements, which integrate a fragment of DNA into a target site in the genome. 

The transposase is modified by donor and helper plasmids that contribute to stability. The 

process results in two copies of the transposable element and was originally thought to be a 

14 
potential basis for gene drives. Four transposons are frequently used for mosquitoes, and they are 

small but abundant enough to enable random integration. 

CAS9 and gRNA systems for transgenesis in mosquitoes can target specific integration sites. The 

process involves homologous recombination that allows for integration into the chromosomes 

and is the current bases for gene drives. 

Parasite Speaker: David Serre, University of Maryland, Baltimore 

Investigators have applied transgenesis to insert anti-Plasmodium effector molecules that block 

Plasmodium, decreasing the prevalence of the parasite and the intensity of the infection. The 

parasite response to transgenes must be further explored to avoid potential development of 

resistance. Some parasites survive the anti-Plasmodium molecules, raising questions about how 

they persist and whether they remain infectious. scRNA-seq has been used to examine and 

compare the genetic expression profiles of parasites throughout their development in the 

mosquito. Current studies highlight the heterogeneity among parasites at the same anatomical 

location, which might explain variability in infection intensity and shed light on parasite 

responses to transgenes. 

Improved understanding of the parasite’s response can guide selection of the most promising 

transgenes; enable optimization by identifying when and where the effector should be expressed; 

and reveal ways to combine transgenes to increase their effect. Evaluating resistance in the 

laboratory and the molecular pathways underlying it can provide information about the 

likelihood of resistance emerging, especially in natural populations. With the extensive 

characterization of genetic diversity in multiple Plasmodium populations, investigators can 

identify populations most susceptible to developing resistance. Studying resistance in the 

laboratory could identify biomarkers associated with resistance before transgenes are deployed in 

the field. 

Among the challenges ahead are determining whether a safe, effective, and sustainable genetic 

vector control can be developed, as well as what constitutes effectiveness. Investigators need 

living strain resource repositories to support research. Some opportunities in the field are as 

follows: 

• Probe mosquito/parasite interactions for vulnerabilities amenable to genetic targeting. 

• Develop surrogate assays to validate P. falciparum-resistant mosquitoes. 

• Develop and test genetic mitigation strategies in anopheline mosquitoes. 

Microbiome/Paratransgenesis 

Vector Speaker: Rita Rio, West Virginia University 

Advancing paratransgenesis requires understanding the biology of the microbiota. Within 

parasite/vector systems, symbiont type, location, and mode of transmission vary. Although 

genetic tools for assessment are readily available to culture and transform Sodalis glossinidius 

bacteria (a symbiont of the tsetse fly), for example, few exist for other symbionts. Another tsetse 

fly symbiont, Wigglesworthia glossinidia, is pivotal to tsetse fly nutrition and immunity, most 

notably providing B vitamins that are important for reproduction, development, and vector 

competence. W. glossinidia also plays a crucial role in immunity. 

15 
 

 

Sodalis precaptivus is a novel candidate for paratransgenesis because it is less susceptible to 

genome degradation than S. glossinidius. When introduced in tsetse flies, it has no effect on the 

fly’s lifespan but does affect the reproductive tissue, resulting in vertical transmission in a single 

generation that continues for subsequent generations. 

Obligate microbes, if available, have high host specificity and transmissibility; they could be 

used as targets or vehicles for paratransgenesis. Some other microbes may be useful for 

paratransgenesis, such as S. glossinidius, which is easy to manipulate using existing tools, or S. 

precaptivus, and lessons learned may be applicable to other insect systems. The effector modules 

may or may not have broad-spectrum effects. 

Bacteria Speaker: Laura Runyen-Janecky, University of Richmond 

Paratransgenesis can target the vector (e.g., with nanobodies that target parasite surface proteins 

essential for development), the parasite (e.g., with bacteria that express antiparasitic proteins or 

molecules), or the symbiont. Because S. glossinidius is related to Escherichia coli, investigators 

have adapted some of the many genetic tools available for E. coli to develop a robust genetic 

toolkit for S. glossinidius that enables horizontal gene transfer, chromosome alteration, and 

transgene expression and product secretion. 

For the trypanosome/tsetse dyad, much is known about biological considerations, but 

investigators have yet to understand the implications of replacing a native insect population with 

a paratransgenic population and the fitness costs to symbiotic systems. Knowledge gaps persist 

around technical aspects. Although a robust genetic tool kit is available for S. glossinidius, such 

resources are lacking for W. glossinidia and other bacteria. The field would benefit from the 

ability to identify more transgene effectors and their specificity. The field also needs a set of 

motor and secretion signals to enable investigators to control when, where, and how transgenesis 

occurs so they can fine-tune paratransgenesis. Implementation of any strategy requires 

understanding how it integrates with other control strategies, as well as recognition of the social, 

environmental, ethical, and regulatory issues, which requires conversations with all stakeholders. 

Discussion 

Participants asked what is known about the fitness impact for the insects, native microbiota, or 

pathogens. Dr. Runyen-Janecky said that elimination of Wigglesworthia has a huge effect on the 

fitness of tsetse because Wigglesworthia provides essential B vitamins to tsetse that are missing 

from the fly’s vertebrate blood-specific diet and that facilitate larval developmental pathways 

essential for immunocompetency during adulthood. Additionally, Wigglesworthia provides 

thiamine to Sodalis, which is important because Sodalis is a thiamine auxotroph. Less is known 

about the effect of Sodalis on tsetse fitness. Elimination of Sodalis has been shown to reduce 

tsetse lifespan. There is a correlation between Sodalis density and trypanosome infection 

prevalence in tsetse; specifically, high densities of Sodalis in the tsetse midgut are correlated 

with the tsetse’s significantly increased susceptibility to infection with trypanosomes. The 

mechanism that underlies this finding is not yet elucidated. 

It was asked which tissues of tsetse S. precaptivus colonize in the transformed tsetse. Dr. Rio 

responded that the gut and reproductive tissue of males and females are infected with S. 

precaptivus, and these infections persist throughout the tsetse lifespan. 

16 
 

 

 

Participants noted that, with respect to malaria parasite development in the mosquito vector and 

the microbiome, colleagues at the biotechnology company Sanaria use aseptic mosquitoes for P. 

falciparum sporozoite production, and there appears to be no requirement for additional 

microbes for their development. 

Session 3: Tools to Accelerate Research 

Introduction to Session 3 

Steve Tsang, Office of Data Science and Emerging Technologies (ODSET), NIAID 

Computational and informatics research at NIAID is driven by basic and clinical scientific 

research needs; they generate large, diverse data sets and novel technological solutions. Genomic 

resources, systems biology, and modeling can be used to accelerate development and discovery 

in vector biology and parasitology. 

Tools for Managing, Integrating, and Mining Complex Datasets 

Eukaryotic Pathogen, Vector, and Host Informatics Resource (VEuPathDB) - Mary Ann 

McDowell, University of Notre Dame 

VEuPathDB (https://veupathdb.org) is a NIAID-funded Bioinformatics Resource Center that 

offers data along with resources to use those data. More than 230 species are supported, and the 

database facilitates queries about orthological relationships. Eventually, VEuPathDB will merge 

with the Clinical Epidemiology Resources Database (ClinEpiDB, https://clinepidb.org/ce/app/) 

and the Microbiome Database (Microbiome DB, https://microbiomedb.org/mbio/app). It has 

1,700 datasets; new datasets and new tools are added every few months. Genome sequence and 

annotation data, phenotypes, field and clinical data, and numerous other data types are supported. 

VEuPathDB provides a range of analytical tools that can be applied to the supported datasets or 

to one’s own data. Tools include Apollo, BLAST, and MapVEu, which supports global data 

analysis. Dr. McDowell walked through some of the search capacities and filtering systems 

available to help users of VEuPathDB find the information they want. In addition to online 

tutorials and educational materials, webinars, and workshops, VEuPathDB hosts virtual trainings 

for laboratories on request. Investigators are encouraged to contact VEuPathDB with questions, 

suggestions, and proposals for new datasets to add (https://veupathdb.org/veupathdb/app/contactus). 

Clinical Epidemiology Database (ClinEpiDB) - David Roos, University of Pennsylvania 

NIAID’s Vaccine Resource Center ensures that a wealth of genomic and transcriptomic 

information is accessible for discovery and translation and provides tools for identifying and 

comparing data. Data can be mined to identify genes of interest and to conduct in silico 

experiments. To address the difficulty of comparing disparate epidemiologic datasets, NIAID has 

embarked on semantic harmonization efforts, motivated, for example, by the work of the 

International Centers for Excellence in Malaria Research to establish common definitions. 

ClinEpiDB leverages the infrastructure and tools created for VEuPathDB to facilitate access, 

comparison, and mining of epidemiological data sets. Users can craft searches and analyze 

variables to assist with investigations and even generate new hypotheses. 

17 
 

 

 

 

Discussion 

Participants noted that many vectors also transmit viruses and asked how such datasets could be 

linked. Dr. McDowell said she is working closely with VEuPathDB’s sister entity, the NIAIDfunded Bacterial and Viral Bioinformatics Resource Center (https://www.bv-brc.org/), to identify 

use cases and combine resources. 

It was asked whether at some point vector microbiota or endosymbiont genomes may be linked. 

Dr. McDowell said the first mosquito microbiome dataset would be released shortly, and there is 

interest to host additional datasets on MicrobiomeDB. Dr. McDowell added that the power of the 

three NIAID-funded databases lies in the harmonization of ontologies and the common 

underlying infrastructure, which makes data interoperable across the three platforms. 

Participants asked whether a similar resource is available for ticks and sand flies. Dr. Roos 

responded that both are included in VectorBase (https://vectorbase.org/vectorbase/app) and he 

added that Leishmania genomics data are supported by TriTrypDB 

(https://tritrypdb.org/tritrypdb/app) both databases are components of VEuPathDB). A 

leishmaniasis skin microbiome dataset is available in MicrobiomeDB, but no leishmaniasis data 

are yet available in ClinEpiDB. Dr. Roos said the platform is very well suited to the complex 

interplay between host/vector/pathogen genetics, biochemistry, and immunology, so, is keen to 

talk with those who may have field or clinical leishmaniasis datasets appropriate for ClinEpiDB. 

Roos noted that he would also be happy to discuss adding tick microbiome data to 

MicrobiomeDB and field study data to ClinEpiDB. 

There was a discussion about the data, with participants pointing out that that the data, especially 

from population studies, are very heterogeneous, and it could be a mistake to try to harmonize 

them. The most an ontology can hope to do is aggregate the data and draw attention to the 

differences in definitions, study designs, and other features. Dr. McDowell said that, for the 

population data, harmonization focuses mostly on enabling users to identify data. She agreed that 

it can be difficult to harmonize different population studies but noted that individuals can explore 

several studies to generate new hypotheses to investigate in a controlled manner. Dr. Roos added 

that ClinEpiDB does not support queries across studies because of the difficulty of harmonizing 

data from complicated datasets from the field. He said that ontologies help to highlight what data 

are available in which studies and enable similar queries against similar datasets but does not 

wish to foster a false sense of confidence by integrating data that cannot be combined. 

Systems Biology Approaches to Manage the Complexity of Parasite/Vector Interactions 

Need for a Systems Biology Approach - Shirley Luckhart, University of Idaho 

Systems biology is needed to understand the complex interface across vectors, pathogens, and 

hosts, with particular attention to the crosstalk between metabolism and the regulation of 

pathogen transmission in arthropods. Arthropods rely on a number of signaling pathways that are 

highly interconnected and together regulate metabolic processes that define resistance, behavior, 

longevity, reproduction, and immunity. Basal and modified states of host metabolism define the 

outcomes of infection and manipulations to enhance host defenses. Research should look at 

variation over time within the individual, within populations, and across populations—for hosts 

and vectors. 

18 
 

 

 

Dr. Luckhart offered an example of how vitamin B5, needed to synthesize coenzyme A, can be 

manipulated to elucidate how variation affects mosquitoes at the individual level, which might be 

an approach to controlling malaria parasite infection within the mosquito. Given the complexity 

of pathogen development in arthropod vectors, researchers can leverage systems biology to 

identify the master regulators in parasite/vector interactions and guide experimental design to 

examine the largest proportion of phenotypic variation in pathogen development. 

Combining Information for a Systems Biology Approach – Adam-Nicolas Pelletier, RPM Bioinfo 

Solutions and Emory University 

Systems biology allows investigators to generate novel insights by combining information from 

various “omics” to build powerful models that can be adapted to the parasite/vector interface. 

The limited amount of biological material is a challenge in arthropod research, so tissue is often 

combined—at the expense of understanding individual variation. Moreover, protocols for the 

isolation of analytes such as metabolites have proven difficult in the past. Spatial transcriptomics 

captures biological heterogeneity in situ, providing context-dependent information that even 

scRNA-seq cannot. This approach can, for example, illustrate at the genetic level where parasites 

are located, what they express, their developmental stages, and their interaction with the vector. 

Other spatial technologies are being developed, such as spatial metabolomics. For example, a 

technique combining fluorescence in situ hybridization with mass spectrometry captures 

molecules and bacterial symbionts in fish. Combining technologies could enable investigators to 

generate models of the parasite/vector interface. 

Discussion 

It was asked what factors are limiting the field from applying the spatial omics technologies to 

vector research. Dr. Luckhart said research has been impeded by the spatial scale and the amount 

of material available. High costs have been a barrier to accessibility, although that is not unique 

to vector biology. There has long been discussion about establishing national resource centers to 

promote sharing of technology that allows researchers to conduct the preliminary work needed 

for grant applications and data publication. Dr. Luckhart hoped this workshop would spur more 

conversation on the idea. 

Modeling Parasite/Vector Interactions to Assist in Target Identification 

Model Characteristics and Considerations - David Smith, University of Washington 

Modeling turns ideas into rigorous equations that describe the processes involved. Models can 

take a statistical approach—identifying patterns based on data, which looks at effects to 

determine potential causes—or a mechanistic approach, in which the cause is presumed, and the 

model demonstrates the effects. Dr. Smith advocated for combining both approaches to close the 

loop, building models for prediction and for testing the conclusions in a broader context. In 

addition, models must take scale into account, recognizing that the processes at one scale create 

effects at another scale. Models for scientific inference identify and codify what is known; 

models for analytics assist with decision making; the differences between the two lie in how each 

deals with uncertainty. The quality of a model can be judged by what the model is intended to 

do, but some key factors include accuracy, utility, and appropriate incorporation of data. 

19 
 

 

Malaria is heavily influenced by local conditions, so it is not clear that what works in one area 

will work in another. Researchers need to understand what does or does not work before they can 

determine whether an approach translates effectively. Smith outlined a model for adaptive 

malaria control that involves an iterative, cyclical process of gathering data to inform action. 

An Environmental Model of Leishmaniasis - Caroline Glidden, Stanford University 

Visceral leishmaniasis has been spreading across Brazil for two decades. Leishmania infantum is 

typically transmitted from flies to dogs. When a host of environmental factors align, the 

pathogen spills over to humans. But the processes are not linear; they occur on multiple scales, 

and a great deal of data are missing. For example, host and vector distribution are affected by 

land use and climate, and vector competence is influenced by temperature. Dr. Glidden used 

machine learning to create models that use environmental data to fill in missing data and 

evaluate which environmental variants are most useful for predicting spillover across different 

land environments. The model performs well and has high specificity. Notably, the most 

predictive variables are land type and temperature. 

The model was intended to generate hypotheses, which are now being tested via a mechanistic 

model. For example, the first model identified that sand flies become infectious after feeding in a 

given air temperature, and the second model will estimate infections by air temperature over 

time. Once the model is created, other environmental variables can be incorporated to enhance 

the ability to predict changes in disease spread according to land type and use and climate 

change. 

Discussion 

Participants appreciated the challenge of determining what kinds of observations are transferable. 

It was asked what datasets were used for training the machine learning model assessing 

leishmaniasis in Brazil and how accurate the model has been at predicting spillover when applied 

retroactively. Dr. Beverley noted that data on leishmaniasis come from clinical cases and 

represent just the tip of the iceberg of Leishmania infections; some studies indicate that 

infections are 10-fold to 50-fold higher than cases. Dr. Beverley also pointed out that, 

increasingly, many mammals other than dogs are being implicated as Leishmania hosts. 

Dr. Glidden responded that she has been using ERA5 climate data, MapBiomas land-use data, 

and United Nations population data. So far, these sources have been quite accurate at 

retroactively predicting pathogen spillover. The out-of-sample area under the receiving operator 

characteristics curve is on average 0.86 (model trained with 80% of data and validated with 20% 

of data). Dr. Glidden added that she is also developing a model that uses machine learning to 

identify reservoir hosts and vectors and then will evaluate their contribution to transmission via 

the spillover model. 

It was noted that data will rarely identify more than the tip of an iceberg. Models can assist with 

synthesis, which generally helps identify critical knowledge and data gaps and quantify 

uncertainty. Participants said Dr. Glidden’s studies are an outstanding example of how to make 

the most of existing cheap and available data. Dr. Beverley clarified that the model maps disease, 

20 
 

 

rather than parasites, which is not a problem if the relationship between infection and disease is 

constant, but it may not be. 

Informatics Research at NIAID: Opportunities and Challenges in Vector-Borne Disease 

Research - Steve Tsang, ODSET, NIAID 

ODSET builds partnerships across NIAID to harness the power of data for research. As more 

data are generated, enabling discovery involves encouraging investigators to use and reuse the 

valuable data collected. ODSET aims to make research more findable, accessible, interpretable, 

and reusable—or FAIR—and more robust. 

A number of informatics funding opportunities are available 

(https://www.niaid.nih.gov/research/data-science-funding-opportunities). Three trans-NIAID 

technology development funding opportunities support exploratory data science methods and 

algorithm development (https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-21-035.html); 

early-stage development of data science technologies (https://grants.nih.gov/grants/guide/rfafiles/RFA-AI-21-020.html), and enhancement or sustainment of data science tools for infectious 

and immune-mediated diseases (https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-21-

021.html). For data reuse, a notice of special interest is available to support secondary analysis of 

existing datasets for advancing immune-mediated and infectious disease research 

(https://grants.nih.gov/grants/guide/notice-files/NOT-AI-21-011.html). 

For workforce development, NIAID and the National Heart, Lung, and Blood Institute offer a 

summer institute for research education in biostatistics and data science to complement and 

enhance training (https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-22-009.html). A Small 

Business Innovation Research contract supports the development of informatics tools 

(https://www.niaid.nih.gov/grants-contracts/2021-sbir-contract-solicitation). The National 

Science Foundation’s Smart and Connected Health vehicle supports research involving artificial 

intelligence and advanced data science (https://grants.nih.gov/grants/guide/notice-files/NOTOD-21-011.html). 

With more projects generating large, diverse, complex data sets, NIH and NIAID recognize the 

need for data that align with the FAIR principles and for innovative, sustainable technology 

solutions. NIAID encourages repositories to follow the principles of transparent, responsible, 

user-focused, sustainable technology—or TRUST—as a framework to implement best practices 

and enhance digital preservation by all stakeholders. Finally, there is a critical need to transform 

data into knowledge by accelerating research in many areas. 

Discussion: Leveraging Tools for Research 

Participants pointed out that a tool is only as good as the data it incorporates and asked how to 

assess the quality of data sets. Dr. Tsang replied that ODSET seeks to raise awareness about NIH 

policies and best practices for data management and sharing, which support quality control. 

It was also asked how ODSET is working with investigators to help improve interoperability 

across systems, such as supporting curation within grantee institutions. Dr. Tsang responded that 

ODSET works with NIAID program officers to help them understand NIH policies. 

21 
 

Participants discussed the U.S. government’s research funding approach and difficulties in 

obtaining population-level information. It was asked how to get funding to support 

understanding of the vector ecology for diseases. Dr. Tsang responded that the trans-NIAID 

technology development funding calls for a computational approach but leaves the scientific 

question open, so applicants could propose a mechanism for vector ecology. 

Participants observed that it is difficult to create multiscale models that combine ecological and 

organism data and allow the user to toggle between infectious disease epidemiology and ecology. 

They noted that NIAID funding opportunities are nicely attuned for certain research aspects, but 

there may be a gap in implementation. 

Dr. Ramalho-Ortigão said that NIH has partnered with the U.S. Department of Defense (DoD) 

for various areas of research, and such collaborations could be used for population and ecology 

research in the future. 

Participants pointed out that although there is broad support for the concept of FAIR data access, 

the easier it is to reuse data, the easier it is to misuse data. Minimizing the potential for 

inadvertent misinterpretation is a major preoccupation for all the data-mining resources. Dr. 

Smith responded that he believes it is a mistake to try to regulate misuse of data; rather, 

resources should highlight the heterogeneity of the data. 

It was emphasized that there is a need for more funding for work at the organism and population 

levels. Dr. McDowell pointed to the emerging infectious diseases program supported by the 

National Science Foundation and NIAID. Participants noted it was highly focused on basic rather 

than applied research. 

Finally, it was noted that vector ecology is a neglected issue. Dr. Roos added that disease 

ecology in general is neglected. 

Reports from the Breakout Groups 

On day two, participants met in groups for approximately 90 minutes to identify limitations, 

opportunities, mechanisms for enhancing target discovery, and research priorities from the 

research community perspective for five parasite/vector pairs. 

Mosquito-Borne Diseases 

Limitations 

• Little is known about mosquito/pathogen interactions (e.g., what the pathogen requires 

for development). 

• Performing mosquito infections is difficult and requires expertise in rearing and an 

insectary. 

• Transgenic and field-derived mosquitoes cannot be cryopreserved. 

• There is limited access to field or semi-field sites to perform assays and studies. 

Opportunities 

• Develop in vivo and in vitro models to study pathogen/mosquito interactions outside of 

an insectary. 

22 
 

 

 

• Establish a central facility for mosquito storage and preservation. 

• Develop standardized protocols for assays. 

• Develop simplified procedures for transgenesis. 

• Create resources to facilitate interaction and collaboration within and across fields (e.g., 

connect basic scientists with modelers). 

Mechanisms for Enhancing Target Discovery 

• Development of in vivo and in vitro models and tissue systems to study 

pathogen/mosquito interaction. 

• Use of bioengineered tissues or 3D-printed tissue platforms. 

Identified Research Priority Areas 

• Develop in vivo and in vitro models to study pathogen/mosquito interaction. 

• Develop ability and facility for long-term storage of transgenic and field mosquitoes. 

Sand Fly-Borne Diseases 

Limitations 

• There is a lack of reliable field studies to understand sand fly ecology and epidemiology. 

• Genetic tools for sand flies are limited. 

• Sand fly colonies are difficult to rear and maintain, and few laboratories do so. 

• There is limited access to animal facilities and the regulatory requirements of keeping 

animals pose barriers. 

• There is no robust regulatable genetic system for Leishmania. 

• The field lacks standardization of culturing Leishmania lifecycle stages. 

• Shipping materials is difficult. 

Opportunities 

• Use transposons (e.g., piggyBac) for genetic manipulation. 

• Provide training and travel grants for investigators to learn how to maintain sand fly 

colonies. 

• Apple single-cell sequencing, especially in situ, to better understand the lifecycle of 

Leishmania in the midgut, for example. 

• Discover a lifecycle regulatory switch for Leishmania. 

• Conduct microbiome studies, especially in the field. 

• Use antiparasitics in the vector. 

• Use the NIAID-funded BEI Resources Repository for distributing material 

(https://www.niaid.nih.gov/research/bei-resources-repository). 

• Use the Drugs for Neglected Diseases Initiative for drug development (https://dndi.org). 

• Apply a One Health approach. 

Mechanisms for Enhancing Target Discovery 

• Effective genetic tools for research on sand flies. 

• Comparative approaches leveraging information from other organism systems (e.g., 

Drosophila, mosquitoes, trypanosomes). 

• Enhanced modeling and genomics training for Leishmania and sand fly researchers. 

23 
 

Identified Research Priority Areas 

• Enhance understanding of sand fly ecology. 

• Develop a regulatable genetic system for Leishmania. 

• Enhance modeling approaches for control interventions. 

Tsetse Fly-Borne Diseases 

Limitations 

• The lack of access to tsetse flies is the main bottleneck for the research community. 

• The United States lacks fly-transmissible RNAi lines for loss-of-function experiments. 

• It is not clear whether the fly and parasite lines available reflect what is in the field in 

terms of microbiota and vector competence. 

• There is a lot of misinformation around the annotation of genomic resources. 

• The lack of vertical transmission of the genetically modified microbiome for 

paratransgenesis poses a barrier. 

• Chemotactic and developmental signals in the fly host that enable parasite transmission 

are unknown. 

• There are limited metabolomic, glycomic, and spatial-omic investigations. 

Opportunities 

• A vertically transmitted, ancestral symbiont has been identified. Consider using it for 

paratransgenic lines and modifying tsetse gene expression. 

• Improve annotation through computational approaches. 

• Take advantage of field insectaries available in endemic countries. 

• Expand the research community (e.g., to include Europe and Africa). 

• Apply new imaging approaches to research. 

Mechanisms for Enhancing Target Discovery 

• Whole-genome parasite RNAi in the fly (e.g., RNAi target sequencing) for functional 

genomics. 

• RNAi parasite lines that are transmissible in the fly. 

• Genome curation for parasite and vector. 

• Parasite development in the fly, e.g., lightsheet microscopy, focused ion beam scanning 

electron microscopy, and serial block-face scanning electron microscopy. 

• Symbiont cultures that are cultivatable, modifiable, and vertically transmissible. 

• Understanding of the role of Wigglesworthia symbiosis in parasitism. 

Identified Research Priority Areas 

• Expand biological resources (e.g., parasite lines, symbiotic lines). 

• Expand infrastructure for tsetse resources (for laboratory and field colonies). 

• Expand computational resources (e.g., imaging, curation of data). 

• Conduct functional genomic investigations during transmission cycle (parasite/fly 

interactions). 

24 
 

 

 

Triatomine-Borne Diseases 

Limitations 

• The field lacks genetic tools for the vector and the parasite. 

• There is little understanding about parasite diversity and vector specificity for discrete 

typing units or genetic lineages. 

• The field lacks omics data (especially for the vector). 

• Availability of insect colonies is limited; maintenance is expensive, labor-intensive, and 

limited to a few species. 

• There is little communication between parasite and vector researchers. 

Opportunities 

• Apply or adapt tools from other systems (e.g., inducible systems to alter gene expression 

in the host and CRISPR in the vector). 

• Employ in vivo transcriptomics and scRNA. 

• Organize more scientific meetings for the community. 

• Explore the paratransgenic approach. 

Mechanisms for Enhancing Target Discovery 

• Drug screening in the vector. 

• Identification of vector and parasite targets. 

• Robust regulatory manipulation of both organisms. 

Research Priorities 

• Fill the holes in the basic biology (high priority). 

• Apply tools from other systems. 

• Increase communication within the community. 

• Unify methods for strains and vectors. 

• Address the outstanding needs to enable progression to translational studies. 

Tick-Borne Diseases 

Limitations 

• There is a knowledge gap around emerging and introduced species of ticks and tick-borne 

diseases. 

• There is poor understanding of the ecology of ticks and tick-borne pathogens. 

• Little is known about pathogen/vector interactions. 

• Validation of laboratory models compared with natural systems is needed. 

• There are few consolidated resources to support genomics and transcriptomics. 

• Functional genomics resources and tools are needed: 

o Genomes 

o Computational tools 

o CRISPR 

o Computing power and cloud resources 

• Little research is performed in resource-limited settings (e.g., Africa, Asia, and Central 

and South America). 

25 
 

 

 

 

 

 

 

 

 

 

Opportunities 

• For emerging and introduced species of ticks, evaluate the following: 

o Vector/pathogen/host competence 

o Ecology 

• Distribution and range of ticks and tick-borne diseases is increasing. Evaluate the 

following: 

o Ecology 

o Vector/host competence 

o Coinfections 

• Increase research on the following tick-borne pathogens: 

o Babesia species 

o Powassan or deer tick, Heartland, and other viruses 

o Spotted fever group Rickettsia 

o Borrelia species 

• Develop a consortia for sharing in vitro and in vivo resources. 

• Explore molecular tools for vector and pathogen manipulation. 

Mechanisms for Enhancing Target Discovery 

• Cell lines for target identification of non-model vectors. 

• Identification of markers to target the vector on the vertebrate host (e.g., for anti-vectorbased vaccines). 

• Identification of markers to target the pathogen in the vector or anti-pathogen vaccine. 

Research Priorities 

• Develop infrastructure and consortia for ticks and tick-borne pathogens. 

• Develop molecular tools and in vitro resources for vector manipulation. 

• Establish infrastructure for data analysis and biostatistics for large data sets. 

• Conduct focused research on ecological aspects and vector competence of understudied, 

emerging, and introduced tick species and pathogens. 

Cross-Cutting Themes - Mike O’Neill, DMID, NIAID 

From the discussions and breakout team presentations, several cross-cutting themes and needs 

were identified, including the following examples: 

• Core facilities are needed to generate reagents and organisms (pathogens and vectors) to 

increase consistency and reproducibility. 

• The field of vector/pathogen interactions needs new ideas from a broader audience with 

different perspectives. A web-based platform for linking investigators across research 

specialties might be a good start to enable multidisciplinary collaborations and facilitate 

the exchange of ideas. 

• Better information and data management and sharing are needed across research fields. 

26 
Final Remarks - Adriana Costero-Saint Denis, DMID, NIAID 

The communication platform established for this workshop could serve as vehicle for sharing 

information and promoting collaboration. Participants are encouraged to use it to keep in touch 

with each other and to provide feedback to NIAID. The value of the platform depends on how 

the research community uses it. To join the platform or provide feedback on the workshop, 

please email Dr. Adriana Costero-Saint Denis at acostero@niaid.nih.gov. 

27 
 

 

Appendix A: Participants List 

Full Name Organization 

Aboulfadl, Souhail Institut National d'Hygiène 

(Velo), Enkelejda Institute of Public Health 

Akorli, Jewelna Noguchi Memorial Institute for Medical Research 

Aksoy, Emre Harvard TH Chan School of Public Health 

Aksoy, Serap Yale University 

Amado Cecilio, Pedro NIAID/NIH 

Azad, Abdu University Of Maryland Baltimore 

Bartilol, Brian KEMRI 

Bates, Paul Lancaster University 

Batzer, Darold University of Georgia 

Ben Mamoun, Choukri Yale 

Benoit, Joshua University of Cincinnati 

Bergmann-Leitner, Elke WRAIR 

Beverley, Steve Washington University 

Bosio, Christopher National Institutes of Health 

Bottino-Rojas, Vanessa University of California, Irvine (UCI) 

Braatz, Giulio UNILA 

Brown, Lisa Georgia Southern University 

Bundi, Caroline Ifakara Health Institute 

Burkhardt, Nicole University of Minnesota 

Calit, Juliana University of Sao Paulo, Inst. of Biomedical Science 

Calvo, Eric NIAID/NIH 

Camacho, Emma Johns Hopkins University 

Chae, Keun Texas A&M University 

Chaves, Luis Fernando ICGES 

Chuang, Eleanore NIAID/NIH 

CHUANG, YU-MIN Yale University 

Conley, Anthony NIAID/NIH 

Cruz, Alvaro Belize Vector and Ecology Center 

Cull, Benjamin University of Minnesota 

Curtis, Michael Baylor College of Medicine 

Da Silva, Thais University of São Paulo 

Dada, Nsa Mosquito Microbiome Consortium 

Damasceno, Flavia University of São Paulo 

de Assis, Samuel Federal Univeristy of Latin American Integration 

de Graffenried, Christopher Brown University 

DIAGNE, Cheikh Tidiane IRD 

Dieme, Constentin Wadsworth Center 

Dimopoulos, George Johns Hopkins University 

Donatelli, Tiago NIAID/NIH 

Dorn, Patricia Loyola University New Orleans 

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Drew, Jessi NIAID/NIH 

Dumonteil, Eric Tulane University 

Etheridge, Drew University of Georgia 

Feili-Hariri, Maryam NIAID/NIH 

FERREIRA, TAINA IOC/FIOCRUZ 

Fikrig, Erol Yale University 

Filatov, Serhii Baylor College of Medicine 

Fustec, Benedicte University of Notre Dame du Lac 

Gaitán, Xiomara Alexandra São Paulo University 

Genta, Fernando Fiocruz 

Gill, Ranjodh NIAID/NIH 

Gimenez, Alba Marina Universidade de Sao Paulo 

Glidden, Caroline Stanford University 

Godoy, Raquel René Rachou Institute 

Oswaldo Cruz Foundation (FIOCRUZ) 

Grogan, Christina Duquesne University 

Groshong, Ashley NIAID/NIH 

Guido, Marisa Duquesne University 

Gulia-Nuss, Monika University of Nevada Reno 

Hackstadt, Ted NIAID/NIH 

Hall, B. F. "Lee" NIAID/NIH 

Hamer, Gabriel Texas A&M AgriLife Research 

Hamerly, Timothy University of Florida 

Harrison, Ruby University of Georgia 

Hermance, Meghan University of South Alabama 

Herren, Jeremy icipe 

Hessab Alvarenga, Patricia NIH 

Hill, Kent UCLA 

Hopkins, Corey Univ. of Nebraska Med Center 

Hutter, Jack WRAIR 

I. DE OLIVEIRA, CAMILA FIOCRUZ 

Iniguez, Eva NIAID/NIH 

Jacobs-Lorena, Marcelo Johns Hopkins Univ. 

James, Tony UC Irvine 

Jiang, Le Henry Jackson Foundation 

Joy, Deirdre NIH 

Justi, Silvia Smithsonian Institution 

Walter Reed Army Institute of Research 

Kamhawi, Shaden NIAID/NIH 

Kaura, Taruna PGIMER, Chandigarh 

Kearney, Chris Baylor University 

Klinkenberg, Lee NIAID/NIH 

Lampe, David Duquesne University 

Lander, Noelia University of Cincinnati 

Landfear, Scott Oregon Health & Science University 

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Leger-Abraham, Melissa Harvard Medical School 

Leydet, Brian SUNY-ESF 

Li, Jun Florida International University 

Liao, Hsiao-Mei Naval Medical Research Center 

Lima Bejar, Dianeth Sara UNILA 

liu, Baoying NIAID/NIH 

long, carole NIAID/NIH 

Lorenzo, Marcelo FIOCRUZ Minas 

Lu, Stephen NIH 

Luckhart, Shirley Univ. of Idaho 

Luker, Hailey New Mexico State University 

Macaluso, Kevin University of South Alabama College of Medicine 

Marques, Adriana NIAID/NIH 

Marshall, John UC Berkeley 

Martin-Martin, Ines NIAID/NIH 

Martins, Larissa Laboratory of Bacteriology - NIAID/NIH 

Matoke-Muhia, Damaris KEMRI 

McDowell, Mary Ann VEuPathDB 

McVicar, Molly University of Nevada, Reno 

Minard, Guillaume University of Lyon 

Miura, Kazutoyo NIAID/NIH 

Mo, Annie NIAID/NIH 

Molina-Cruz, Alvaro NIH 

Moussa, Laura FDA/CVM 

Moyer, Adam FDA 

Munderloh, Ulrike University of Minnesota 

Mushegian, Alexandra NIH 

Myler, Peter University of Washington 

Narasimhan, Sukanya Yale University 

Ndawula, Charles National Livestock Resources Research Institute 

Nelson, Suppaluck The Walter Reed Biosystematics Unit 

Nock, Adam NIAID/NIH 

Norris, Laura BMGF 

Nuss, Andrew University of Nevada, Reno 

Oliveira, Fabiano NIH 

ONAYNGO, MARIA Wadsworth 

Pedra, Joe University of Maryland School of Medicine 

Pelletier, Adam-Nicolas RPM Bioinfo Solutions 

Pennington, Pamela Universidad del Valle de Guatemala 

Percopo, Caroline NIAID 

Pineda, José University of San Carlos of Guatemala 

Laboratory of Applied Entomology and Parasitology 

Pinto, Daniel Walter Reed Army Institute of Research 

Raban, Robyn UC San Diego 

Rakotondraibe, Liva Harinantenaina The Ohio State University 

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Ramalho-Ortigao, Marcelo USUHS 

Raman, Vanitha NIAID/NIH 

Ratnayake, Oshani Colorado State University 

Rio, Rita West Virginia Univ. 

Roos, David VEuPathDB 

Runyen-Janecky, Laura Univ of Richmond 

Rutvisuttinunt, Wiriya NIAID/NIH 

Sa, Juliana NIAID/NIH 

Saadi, Soheyla NIAID/NIH 

Salvador neto, Orlando Ufrj - brazil 

Sanchez C, Hector M UC Berkeley 

Schneider, Johanna NIAID/NIH 

Sekaly, Rafick Emory University 

Serre, David Univ. of Maryland, Baltimore 

Shapiro, Stuart NIAID/NIH 

Sharma, Arvind University of Nevada Reno 

Short, Sarah The Ohio State University 

Sinnis, Photini Johns Hopkins School of Public Health 

Smith, David University of Washington 

Smith, Jamie NIAID/NIH 

Smith, Ryan Iowa State University 

Solórzano, Marisé University of São Paulo 

Sonenshine, Daniel NIAID/NIH 

Stevens, Lori Univ of Vermont 

Tirloni, Lucas NIH 

Trevas, Dana Shea & Trevas, Inc. 

Tsang, Steven NIAID/NIH 

Tschudi, Christian Yale University 

Ulloa, Amanda NIAID/NIH 

Valiente Moro, Claire Lyon University 

Vargas, Sandra USP 

Vaughan, Ashley Seattle Childrens Hospital 

Vega-Rodriguez, Joel NIAID/NIH 

Velasquez, Sydney Texas A&M 

Vogel, Kevin University of Georgia 

Voronin, Denis NIAID/NIH 

Weiss, Brian Yale School of Public Health 

Williams, Carla NIH 

Zheng, Liangbiao NIH 

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NIAID Organizers 

Adriana Costero-Saint Denis, NIAID/NIH 

Julio Aliberti, NIAID/NIH 

Venera Barsaku, NIAID/NIH 

Ghiorghis Ghenbot, NIAID/NIH 

Mike O’Neil, NIAID/NIH 

Reed Shabman, NIAID/NIH 

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Appendix B: Resources and Background Materials 

Investigator Resources 

• NIAID’s BEI Resources for vector research (https://www.beiresources.org/Home.aspx) 

suggested search terms: 

o Interventional agent development services 

Preclinical models of infectious diseases 

Therapeutic development services 

o In vitro assessment for antimicrobial activity program 

o Vaccine development services 

• NIAID’s Eukaryotic Pathogen, Vector, and Host Informatics Resource (VEuPathDB) 

o Clinical Epidemiology Resources Database (ClinEpiDB) 

o Microbiome Database (Microbiome DB) 

o VectorBase 

o Kinetoplastids Informatic Resource (TriTrypDB) 

• NIAID’s Bacterial and Viral Bioinformatics Resource Center 

• Drugs for Neglected Diseases Initiative 

Funding Opportunities 

• NIAID Data Science Funding Opportunities 

• NIAID Funding Opportunities 

• NIAID Systems Biology for Infectious Diseases: Request for Applications 

NIAID Information and Contacts 

• NIAID Division of Microbiology and Infectious Diseases (DMID) 

• Preclinical and Clinical Services contacts 

• Within DMID: 

• For any vector control product development and research resources or support 

and for Preclinical Services related questions, contact Ghiorghis Ghenbot at 

ghiorghis.ghenbot@nih.gov. 

• For questions regarding NIH funding mechanisms to support research on 

vectors and vector-borne pathogens, contact Adriana Costero-Saint Denis at 

acostero@niaid.nih.gov. 

• For questions regarding parasite drug discovery and development, contact 

Michael O’Neil at michael.o'neil@nih.gov. 

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Appendix C: List of Selected Key Publications 

Session 1: State of Science for Parasite/Vector Systems 

1. Trypanosome/Tsetse Fly 

• Mammalian African trypanosome VSG coat enhances tsetse’s vector 

competence. 

• A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic 

matrixintegrity and trypanosome transmission success. 

• Developmental Progression to Infectivity in Trypanosoma brucei triggered 

by an RNA-Binding Protein. 

• Identification of positive and negative regulators in the stepwise 

developmentalprogression towards infectivity in Trypanosoma brucei. 

2. Trypanosome/Triatomine Bug 

• From e-voucher to genomic data: Preserving archive specimens as 

demonstrated withmedically important mosquitoes (Diptera: Culicidae) and 

kissing bugs (Hemiptera: Reduviidae). 

• Interactions among Triatoma sanguisuga blood feeding sources, gut 

microbiota andTrypanosoma cruzi diversity in southern Louisiana. 

3. Malaria/Mosquito 

• A Plasmodium key fits a mosquito lock. 

• Mosquito Microbiota and Implications for Disease Control. 

• Type II Fatty Acid Biosynthesis Is Essential for Plasmodium falciparum 

SporozoiteDevelopment in the Midgut of Anopheles Mosquitoes. 

• Driving mosquito refractoriness to Plasmodium falciparum with engineered 

symbioticbacteria. 

• The Plasmodium bottleneck: malaria parasite losses in the mosquito vector. 

4. Leishmania/Sand Fly 

• Sequential blood meals promote Leishmania replication and reverse 

metacyclogenesisaugmenting vector infectivity. 

• Distinct gene expression patterns in vector-residing Leishmania infantum 

identifyparasite stage-enriched markers. 

• Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin 

Inflammationand Promotes Disease Tolerance. 

• Gut Microbes Egested during Bites of Infected Sand Flies Augment 

Severity ofLeishmaniasis via Inflammasome-Derived IL-1beta. 

• Sequential blood meals promote Leishmania replication and reverse 

metacyclogenesisaugmenting vector infectivity. 

• Leishmaniasis: The act of transmission. 

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Session 2: Approaches to Target the Parasite within the Vector 

1. Exposure to Antiparasitics: Ingestion Route 

• An integrated overview of the midgut bacterial flora composition of 

Phlebotomus perniciosus, a vector of zoonotic visceral leishmaniasis in the 

Western Mediterranean. 

• Zoonotic visceral leishmaniasis transmission: modeling, backward 

bifurcation, andoptimal control. 

• Bacterial Infection and Immune Responses in Lutzomyia longipalpis Sand 

Fly LarvaeMidgut. 

• Evaluation of two sexual-stage antigens as bivalent transmission-blocking 

vaccines inrodent malaria. 

• The transmission-blocking effects of antimalarial drugs revisited: fitness 

costs andsporontocidal effects of artesunate and sulfadoxinepyrimethamine. 

• Transgenic pyrimethamine-resistant plasmodium falciparum reveals 

transmission-blocking potency of P218, a novel antifolate candidate drug. 

• Transmission blocking sugar baits for the control of Leishmania development 

inside sandflies using environmentally friendly beta-glycosides and their 

aglycones. 

2. Exposure to Antiparasitics: Non-Ingestion Route 

• Discovery and characterization of 2-nitro-5-(4-(phenylsulfonyl)piperazin-1-

yl)-N- (pyridine4ylmethyl)anilines as novel inhibitors of the Aedes aegypti 

(AeKir1) channel. 

• An insecticide resistance-breaking mosquitocide targeting inward rectifier 

potassiumchannels in vectors of Zika virus and malaria. 

• Discovery and characterization of a potent and selective inhibitor of Aedes 

aegypti inward rectifier potassium channels. 

• Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium 

parasitetransmission. 

• Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance 

to malariacontrol strategies. 

3. Transgenics 

• Population modification of Anopheline species to control malaria transmission. 

• Next generation gene drive for population modification of the malaria vector 

mosquito,Anopheles gambiae. 

• Efficient population modification gene-drive rescue system in the malaria 

mosquitoAnopheles stephensi. 

• Transcriptional heterogeneity and tightly regulated changes in gene expression 

during Plasmodium berghei sporozoite development. 

• Single-cell transcription analysis of Plasmodium vivax blood-stage parasites 

identifies stage- and species-specific profiles of expression. 

• Genomic Analyses Reveal the Common Occurrence and Complexity of 

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Plasmodium vivaxRelapses in Cambodia. 

4. Microbiome/Paratransgenesis 

• Delivery of a functional anti-trypanosome Nanobody in different tsetse fly 

tissues viaabacterial symbiont, Sodalis glossinidius. 

• Engineering insects from the endosymbiont out. 

• Genetic Modification of Sodalis Species by DNA Transduction 

• Self-limiting paratransgenesis. 

Session 3: Tools to Accelerate Research 

1. Genomic Resources 

• ClinEpiDB: an open-access clinical epidemiology database resource 

encouraging onlineexploration of complex studies. 

• MicrobiomeDB: a systems biology platform for integrating, mining and 

analyzingmicrobiome experiments. 

• VEuPathDB 

• Advances in omics-based methods to identify novel targets for malaria 

and otherparasitic protozoan infections 

• The transcriptome of circulating sexually committed Plasmodium falciparum 

ring stageparasites forecasts malaria transmission potential 

2. Systems Biology 

• A systems approach to infectious disease 

• Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins 

Important forMalaria Transmission to Mosquitoes 

• Mapping Arbovirus-Vector Interactions Using Systems Biology Techniques 

3. Modeling 

• Why Model Malaria? 

• Human mobility patterns and malaria importation on Bioko Island 

• A New Test of a Theory about Old Mosquitoes 

• Evolutionary consequences of feedbacks between within-host competition and 

diseasecontrol 

4. Data Science 

• Infectious Disease Research in the Era of Big Data 

• Artificial Intelligence for infectious disease Big Data Analytics 

36