Safety and efficacy of continuous terlipressin infusion in HRS-AKI in a transplant population.

BACKGROUND AND AIMS: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and as such was assessed in a population comprised of liver transplant (LT) candidates. METHODS AND RESULTS: Fifty hospitalized, LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. ACLF grade 3, serum creatinine (SCr)>5.0 mg/dL, or MELD≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide (M&O) or norepinephrine (NorEpi) for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as ≥30% decrease in SCr with EOT SCr≤1.5, partial response (PR) as ≥30% decrease in SCr with EOT SCr>1.5, and non-response (NR) as <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p<0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p=0.12; D90: 78% vs. 68%, p=0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p<0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p<0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. CONCLUSIONS: With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical M&O/NorEpi cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

What, How, When, and Where: Spatiotemporal Water Quality Hazards of Cyanotoxins in Subtropical Eutrophic Reservoirs.

Though toxins produced during harmful blooms of cyanobacteria present diverse risks to public health and the environment, surface water quality surveillance of cyanobacterial toxins is inconsistent, spatiotemporally limited, and routinely relies on ELISA kits to estimate total microcystins (MCs) in surface waters. Here, we employed liquid chromatography tandem mass spectrometry to examine common cyanotoxins, including five microcystins, three anatoxins, nodularin, cylindrospermopsin, and saxitoxin in 20 subtropical reservoirs spatially distributed across a pronounced annual rainfall gradient. Probabilistic environmental hazard analyses identified whether water quality values for cyanotoxins were exceeded and if these exceedances varied spatiotemporally. MC-LR was the most common congener detected, but it was not consistently observed with other toxins, including MC-YR, which was detected at the highest concentrations during spring with many observations above the California human recreation guideline (800 ng/L). Cylindrospermopsin was also quantitated in 40% of eutrophic reservoirs; these detections did not exceed a US Environmental Protection Agency swimming/advisory level (15,000 ng/L). Our observations have implications for routine water quality monitoring practices, which traditionally use ELISA kits to estimate MC levels and often limit collection of surface samples during summer months near reservoir impoundments, and further indicate that spatiotemporal surveillance efforts are necessary to understand cyanotoxins risks when harmful cyanobacteria blooms occur throughout the year.

Concentration of total microcystins associates with nitrate and nitrite, and may disrupt the nitrogen cycle, in warm-monomictic lakes of the southcentral United States.

Cyanobacterial blooms and the toxins they produce pose a growing threat worldwide. Mitigation of such events has primarily focused on phosphorus management and has largely neglected the role of nitrogen. Previous bloom research and proposed management strategies have primarily focused on temperate, dimictic lakes, and less on warm-monomictic systems like those at subtropical latitudes. The in-lake conditions, concentration of total microcystins, and microbial functioning of twenty warm-monomictic lakes in the southcentral United States were explored in the spring and summer of 2021. Our data revealed widespread microcystins in lakes across this region, some of which exceeded regulatory limits. Microcystins were higher in the spring compared to the summer, indicating that warm-monomictic lakes, even across a large range of precipitation, do not follow the trends of temperate dimictic lakes. Microcystins were found in surface waters and bottom waters well below the photic zone, reflecting the persistence of these toxins in the environment. Principal components analyses showed a strong association between microcystins, nitrate + nitrite, and Planktothrix relative abundance and transcriptional activity. Many systems exhibited stronger denitrification in the spring, perhaps contributing to the decreased toxin concentrations in the summer. Counter to most sampled lakes, one lake with the highest concentration of total microcystins indicated nitrogen cycle disruption, including inhibited denitrification. These findings are relevant to mitigating cyanobacterial blooms and toxin production in warm-monomictic systems, and suggests a need to consider nitrogen, and not solely phosphorus, in nutrient management discussions.

Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology.

Genomic data can be used to track the transmission and geographic spread of infectious diseases. However, the sequencing capacity required for genomic surveillance remains limited in many low- and middle-income countries (LMICs), where dog-mediated rabies and/or rabies transmitted by wildlife such as vampire bats pose major public health and economic concerns. We present here a rapid and affordable sample-to-sequence-to-interpretation workflow using nanopore technology. Protocols for sample collection and the diagnosis of rabies are briefly described, followed by details of the optimized whole genome sequencing workflow, including primer design and optimization for multiplex polymerase chain reaction (PCR), a modified, low-cost sequencing library preparation, sequencing with live and offline base calling, genetic lineage designation, and phylogenetic analysis. Implementation of the workflow is demonstrated, and critical steps are highlighted for local deployment, such as pipeline validation, primer optimization, inclusion of negative controls, and the use of publicly available data and genomic tools (GLUE, MADDOG) for classification and placement within regional and global phylogenies. The turnaround time for the workflow is 2-3 days, and the cost ranges from $25 per sample for a 96 sample run to $80 per sample for a 12 sample run. We conclude that setting up rabies virus genomic surveillance in LMICs is feasible and can support progress toward the global goal of zero dog-mediated human rabies deaths by 2030, as well as enhanced monitoring of wildlife rabies spread. Moreover, the platform can be adapted for other pathogens, helping to build a versatile genomic capacity that contributes to epidemic and pandemic preparedness.

Making genomic surveillance deliver: A lineage classification and nomenclature system to inform rabies elimination.

The availability of pathogen sequence data and use of genomic surveillance is rapidly increasing. Genomic tools and classification systems need updating to reflect this. Here, rabies virus is used as an example to showcase the potential value of updated genomic tools to enhance surveillance to better understand epidemiological dynamics and improve disease control. Previous studies have described the evolutionary history of rabies virus, however the resulting taxonomy lacks the definition necessary to identify incursions, lineage turnover and transmission routes at high resolution. Here we propose a lineage classification system based on the dynamic nomenclature used for SARS-CoV-2, defining a lineage by phylogenetic methods for tracking virus spread and comparing sequences across geographic areas. We demonstrate this system through application to the globally distributed Cosmopolitan clade of rabies virus, defining 96 total lineages within the clade, beyond the 22 previously reported. We further show how integration of this tool with a new rabies virus sequence data resource (RABV-GLUE) enables rapid application, for example, highlighting lineage dynamics relevant to control and elimination programmes, such as identifying importations and their sources, as well as areas of persistence and routes of virus movement, including transboundary incursions. This system and the tools developed should be useful for coordinating and targeting control programmes and monitoring progress as countries work towards eliminating dog-mediated rabies, as well as having potential for broader application to the surveillance of other viruses.

There's more to RNA viruses than diseases.

A simple, pervasive biological entity in the ocean sheds light on evolution.

A Single-Center Study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Recurrence in Recipients of Liver Transplant for Treatment of Nonalcoholic Steatohepatitis Cirrhosis.

OBJECTIVES: Nonalcoholic steatohepatitis is a growing indication for liver transplant. We examined multiple granular elements to determine risk factors for recurrence of nonalcoholic steatohepatitis or recurrence of nonalcoholic fatty liver disease. MATERIALS AND METHODS: This is a retrospective, single-center study of patients who underwent liver transplant for nonalcoholic steatohepatitis. Demographic differences were assessed with the Wilcoxon and Pearson tests for continuous and discrete variables, respectively. We used a linear mixed effects model to estimate mean changes in body mass index and laboratory measurements. Time to graft loss was analyzed with the Cox proportional hazards model. RESULTS: From 1998 to 2017, there were 275 patients at our center who underwent liver transplant as treatment for nonalcoholic steatohepatitis cirrhosis. Of these patients, 31 (11%) were diagnosed with recurrent nonalcoholic steatohepatitis and 60 (22%) had recurrent nonalcoholic fatty liver disease. Patients with or without recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease were similar with regard to Model for End-Stage Liver Disease score, body mass index, sex, ethnicity, comorbidity, and donor characteristics, including donor macrosteatosis. Exposures to several medication classes were examined, but there was no association with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. Changes in aspartate aminotransferase and alanine aminotransferase levels over time were correlated with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease versus levels observed in the groups with no recurrent disease. There was no difference in graft survival for the groups with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. CONCLUSIONS: Recurrence of nonalcoholic fatty liver disease and recurrence of nonalcoholic steatohepatitis were not associated with increased mortality after liver transplant. There were notable steady increases in body mass index after transplant for all patients who received liver transplant as treatment for nonalcoholic steatohepatitis.

Nitrogen sourcing during viral infection of marine cyanobacteria.

The building blocks of a virus derived from de novo biosynthesis during infection and/or catabolism of preexisting host cell biomass, and the relative contribution of these 2 sources has important consequences for understanding viral biogeochemistry. We determined the uptake of extracellular nitrogen (N) and its biosynthetic incorporation into both virus and host proteins using an isotope-labeling proteomics approach in a model marine cyanobacterium Synechococcus WH8102 infected by a lytic cyanophage S-SM1. By supplying dissolved N as 15N postinfection, we found that proteins in progeny phage particles were composed of up to 41% extracellularly derived N, while proteins of the infected host cell showed almost no isotope incorporation, demonstrating that de novo amino acid synthesis continues during infection and contributes specifically and substantially to phage replication. The source of N for phage protein synthesis shifted over the course of infection from mostly host derived in the early stages to more medium derived later on. We show that the photosystem II reaction center proteins D1 and D2, which are auxiliary metabolic genes (AMGs) in the S-SM1 genome, are made de novo during infection in an apparently light-dependent manner. We also identified a small set of host proteins that continue to be produced during infection; the majority are homologs of AMGs in S-SM1 or other viruses, suggesting selective continuation of host protein production during infection. The continued acquisition of nutrients by the infected cell and their utilization for phage replication are significant for both evolution and biogeochemical impact of viruses.

Outcome of Tibial Closing Wedge Osteotomy in 55 Cranial Cruciate Ligament-Deficient Stifles of Small Dogs (<15 kg).

OBJECTIVE: To describe the outcome of cranial closing wedge osteotomy (CWO) of the tibia for treatment of cranial cruciate ligament (CrCL)-deficient stifles in dogs with a body weight of <15 kg. STUDY DESIGN: Retrospective case series. ANIMALS: Forty-five client-owned dogs (n=55 stifles). METHODS: Medical records (2005-2014), radiographs, and owner questionnaire were used to identify the surgical procedure performed, associated complications and outcome in 45 dogs undergoing CWO in 55 stifles. RESULTS: Data for 55 stifles from 45 dogs were included. Bichon Frise was the most frequent dog breed (n=11). Mean pre- and postoperative tibial plateau angle (TPA) were 36.3° (95% CI 35.1-37.5) and 7.5° (95% CI 6.7-8.2), respectively. Pin and tension bands were placed in 38/55 stifles (69%). The most frequent complication at short-term follow-up (2 weeks) was incisional complications in 8 stifles; all resolved with systemic antibiotic administration alone. Data were available for all stifles at 8 week follow-up with an overall complication occurrence in 16/55 stifles (28%); 1 dog required revision surgery. Tibial osteotomy healing was evident on radiographs at 8 weeks postoperative in 53 stifles (96%), considered complete in 27 stifles, and good in 26 stifles. Follow-up owner questionnaire was available for 36 dogs at a mean of 24 months and 34/36 owners (94%) were satisfied with the procedure and considered their dog had a good quality of life with minimal long-term complications. CONCLUSION: Dogs with a body weight <15 kg undergoing CWO for treatment of a CrCL-deficient stifle had a good outcome based on clinical status, radiographic evaluation, and owner questionnaire.

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents.

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process.

An examination of the differences between two methods of estimating energy expenditure in resistance training activities.

To date, few studies have looked at the energy expenditure (EE) of individual resistance training (RT) exercises. The purpose of this study was to evaluate the EE of 4 modes of RT (push-ups, curl-ups, pull-ups, and lunges) using 2 different calculation methods for estimating EE. Twelve healthy men with a minimum of 1 year of RT experience were randomly assigned to an RT circuit. Each circuit contained the 4 RT exercises in a specified order. The participants completed 3 trials of their assigned circuit during one visit to the laboratory. Oxygen consumption was measured continuously throughout the trial using indirect calorimetry. Two different calculation methods were applied to estimate EE. Using the traditional method (TEC), we estimated EE by calculating the average oxygen consumption recorded during each activity. Using the second, nontraditional method (NEC), we estimated EE by calculating the average oxygen consumption recorded during the recovery period. Independent T-tests were used to evaluate mean EE differences between the 2 methods. Estimates of EE obtained from the NEC were significantly higher for all the 4 activities (p < 0.001). Using the NEC, 3 of the 4 activities were classified as vigorous intensity (push-ups: 6.91 metabolic equivalents (METs); lunges: 7.52 METs; and pull-ups: 8.03 METs), whereas none were classified as vigorous using the TEC. Findings suggest that the methods we use to calculate the EE of anaerobic activities significantly affect EE estimates. Using the TEC may underestimate actual EE of anaerobic activities.

Protein phosphatase 4 is phosphorylated and inactivated by Cdk in response to spindle toxins and interacts with γ-tubulin.

Many pharmaceuticals used to treat cancer target the cell cycle or mitotic spindle dynamics, such as the anti-tumor drug, paclitaxel, which stabilizes microtubules. Here we show that, in cells arrested in mitosis with the spindle toxins, nocodazole, or paclitaxel, the endogenous protein phosphatase 4 (Ppp4) complex Ppp4c-R2-R3A is phosphorylated on its regulatory (R) subunits, and its activity is inhibited. The phosphorylations are blocked by roscovitine, indicating that they may be mediated by Cdk1-cyclin B. Endogenous Ppp4c is enriched at the centrosomes in the absence and presence of paclitaxel, nocodazole, or roscovitine, and the activity of endogenous Ppp4c-R2-R3A is inhibited from G 1/S to the G 2/M phase of the cell cycle. Endogenous γ-tubulin and its associated protein, γ-tubulin complex protein 2, both of which are essential for nucleation of microtubules at centrosomes, interact with the Ppp4 complex. Recombinant γ-tubulin can be phosphorylated by Cdk1-cyclin B or Brsk1 and dephosphorylated by Ppp4c-R2-R3A in vitro. The data indicate that Ppp4c-R2-R3A regulates microtubule organization at centrosomes during cell division in response to stress signals such as spindle toxins, paclitaxel, and nocodazole, and that inhibition of the Ppp4 complex may be advantageous for treatment of some cancers.

Towards a better integration of global health and biodiversity in the new sustainable development goals beyond Rio+20.

In June 2012, Brazil hosted Rio+20, the United Nations Conference on Sustainable Development (UNCSD) marking the 20th anniversary of the 1992 Earth Summit. The Rio+20 outcome document entitled The future we want provides general guidance to shape sustainable development policies, but fell short of providing legally binding agreements or pragmatic goals. Negotiators agreed to develop a process for the establishment of new Sustainable Development Goals (SDGs), building upon the Millennium Development Goals, and setting the foundation for the post-2015 UN development agenda. Our objective is to argue that discussions beyond Rio+20 and toward the adoption of SDGs offer a critical opportunity to re-assess the major challenges for global health and sustainable development. There is an urgent need to translate the general aspirations put forth by Rio+20 into concrete health outcomes and greater health equity. The way toward the post-2015 SDGs will likely be more effective if it highlights the full gamut of linkages between ecosystem processes, anthropogenic environmental changes (climate change, biodiversity loss, and land use), socio-economic changes, and global health. Negotiations beyond Rio+20 should strongly acknowledge the global health benefits of biodiversity protection and climate change mitigation and adaptation strategies, which reduce diseases of poverty and protect the health of the most vulnerable. We argue that health and ecosystems are inextricably linked to all development sectors and that health should remain a critical priority for the upcoming SDGs in the context of global environmental change.

Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics.

Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.

Separation of rotavirus double-layered particles and triple-layered particles by capillary zone electrophoresis.

Cell culture derived rotavirus preparations contain a mixture of double-layered particles (DLPs) and triple-layered particles (TLPs). Characterization of rotavirus vaccine products is important to demonstrate a consistent manufacturing process. A capillary zone electrophoresis (CZE) method was developed to separate and quantitate rotavirus DLPs and TLPs in cell lysate samples and CsCl-purified vaccine preparations of each of the five reassortant rotavirus vaccine strains (G1, G2, G3, G4 and P1) contained in the pentavalent rotavirus vaccine, RotaTeq. The CZE electropherograms showed that migration of DLPs and TLPs from both CsCl-purified and cell lysates resulted in a separation distance of approximately 3 min between the two rotavirus particle types. The identification of the peak(s) containing TLPs was confirmed for both CsCl-purified and cell lysate samples by treatment of the samples with 50mM EDTA, which converted TLPs to DLPs. The migration pattern of the DLPs was consistent (23-24 min) among all reassortant strains tested, whether the DLPs were CsCl-purified or from cell lysates. However, the migration pattern of the TLP electropherograms of the reassortant rotavirus strains in cell lysates differed from those of the CsCl-purified reassortant rotavirus strains. In the cell lysate samples, the TLPs of the G1 and G2 reassortant rotavirus strains migrated slower that the corresponding TLPs from the CsCl-purified samples, while the migration time of the TLPs of the G3, G4 and P1 reassortants strains from the cell lysate and CsCl-purified samples appeared similar. Also, the TLPs from the CsCl-purified samples appeared as a defined single peak, while most of the TLPs from the cell lysate samples appeared as a broad peak or as multiple peaks. All the migration patterns were reproducible and consistent. Taking into account reproducibility, objective quantitation, and minimal sample manipulation as well as volume, CZE allowed consistent and quantitative characterization of rotavirus vaccine preparations, which is required for evaluation of vaccine products, including process validation.

VectorBase: a data resource for invertebrate vector genomics.

VectorBase (http://www.vectorbase.org) is an NIAID-funded Bioinformatic Resource Center focused on invertebrate vectors of human pathogens. VectorBase annotates and curates vector genomes providing a web accessible integrated resource for the research community. Currently, VectorBase contains genome information for three mosquito species: Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus, a body louse Pediculus humanus and a tick species Ixodes scapularis. Since our last report VectorBase has initiated a community annotation system, a microarray and gene expression repository and controlled vocabularies for anatomy and insecticide resistance. We have continued to develop both the software infrastructure and tools for interrogating the stored data.

A Purchaser's Guide to Clinical Preventive Services: a tool to improve health care coverage for prevention.

INTRODUCTION: In 2005, representatives from the Centers for Disease Control and Prevention partnered with the National Business Group on Health and the Agency for Healthcare Research and Quality to form a work group for developing A Purchaser's Guide to Clinical Preventive Services: Moving Science into Coverage. This guide, designed as a tool for employers, describes recommended clinical preventive services for 46 conditions. The guide includes the scientific evidence and benefits language that employers need to include comprehensive clinical preventive services in their medical benefit plans. METHODS: The work group determined that the guide would address conditions that 1) affected a large percentage of the working population, 2) were costly to control, and 3) had well-defined and accepted recommendations for preventive services. Subject matter experts from the Centers for Disease Control and Prevention, the National Business Group on Health, and the Agency for Healthcare Research and Quality developed or reviewed statements of scientific evidence for 46 diseases and conditions. RESULTS: The Purchaser's Guide, written for an employer audience, includes descriptions for recommended clinical preventive services and their cost savings, syntheses of supporting evidence, strategies for prioritization, and recommendations to improve the delivery and use of preventive services. Twelve hundred copies were sent to more than 275 members of the National Business Group on Health and other purchasers of health care; training sessions on the Guide were held for 228 business leaders, health benefit consultants, and health plan administrators; and an online version was created through the Web sites of the National Business Group on Health and the Centers for Disease Control and Prevention. The online version has received more than 260,000 hits since its release. CONCLUSION: In 2007, the National Business Group on Health reported that some Fortune 500 companies will be using the Purchaser's Guide when negotiating their health benefit contracts and developing their health care strategies. Further research is under way to determine whether the Guide influences employers to purchase recommended clinical preventive services.

Genome sequence of Aedes aegypti, a major arbovirus vector.

We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.

VectorBase: a home for invertebrate vectors of human pathogens.

VectorBase (http://www.vectorbase.org/) is a web-accessible data repository for information about invertebrate vectors of human pathogens. VectorBase annotates and maintains vector genomes providing an integrated resource for the research community. Currently, VectorBase contains genome information for two organisms: Anopheles gambiae, a vector for the Plasmodium protozoan agent causing malaria, and Aedes aegypti, a vector for the flaviviral agents causing Yellow fever and Dengue fever.