Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-30 (of 106 Records) |
Query Trace: Dotson E [original query] |
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Juvenile hormone as a contributing factor in establishing midgut microbiota for fecundity and fitness enhancement in adult female Aedes aegypti
Taracena-Agarwal ML , Walter-Nuno AB , Bottino-Rojas V , Mejia APG , Xu K , Segal S , Dotson EM , Oliveira PL , Paiva-Silva GO . Commun Biol 2024 7 (1) 687 Understanding the factors influencing mosquitoes' fecundity and longevity is important for designing better and more sustainable vector control strategies, as these parameters can impact their vectorial capacity. Here, we address how mating affects midgut growth in Aedes aegypti, what role Juvenile Hormone (JH) plays in this process, and how it impacts the mosquito's immune response and microbiota. Our findings reveal that mating and JH induce midgut growth. Additionally, the establishment of a native bacterial population in the midgut due to JH-dependent suppression of the immune response has important reproductive outcomes. Specific downregulation of AMPs with an increase in bacteria abundance in the gut results in increased egg counts and longer lifespans. Overall, these findings provide evidence of a cross-talk between JH response, gut epithelial tissue, cell cycle regulation, and the mechanisms governing the trade-offs between nutrition, immunity, and reproduction at the cellular level in the mosquito gut. |
Distribution and dynamics of Anopheles gambiae s.l. larval habitats in three Senegalese cities with high urban malaria incidence
Ndiaye F , Diop A , Chabi J , Sturm-Ramirez K , Senghor M , Diouf EH , Samb B , Diedhiou SM , Thiaw O , Zohdy S , Dotson E , Sene D , Diouf MB , Koscelnik V , Gerberg L , Bangoura A , Clark T , Faye O , Dia I , Konate L , Niang EHA . PLoS One 2024 19 (5) e0303473 Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November-December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP). |
Concurrent transmission of multiple carbapenemases in a long-term acute-care hospital
Rankin DA , Walters MS , Caicedo L , Gable P , Moulton-Meissner HA , Chan A , Burks A , Edwards K , McAllister G , Kent A , Laufer Halpin A , Moore C , McLemore T , Thomas L , Dotson NQ , Chu AK . Infect Control Hosp Epidemiol 2024 1-10 OBJECTIVE: We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying bla(VIM) (VIM-CRPA) and Enterobacterales carrying bla(KPC) (KPC-CRE) at a long-term acute-care hospital (LTACH A). METHODS: We defined an incident case as the first detection of bla(KPC) or bla(VIM) from a patient's clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had bla(KPC,) 11 had bla(VIM,) and 7 had bla(VIM) and bla(KPC). Also, bla(KPC) were identified from 7 Enterobacterales, and all bla(VIM) were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates. CONCLUSIONS: Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission. |
Urban malaria vector bionomics and human sleeping behavior in three cities in Senegal
Diop A , Ndiaye F , Sturm-Ramirez K , Konate L , Senghor M , Diouf EH , Dia AK , Diedhiou S , Samb B , Sene D , Zohdy S , Dotson E , Diouf MB , Koscelnik V , Gerberg L , Bangoura A , Faye O , Clark T , Niang EHA , Chabi J . Parasit Vectors 2023 16 (1) 331 BACKGROUND: Malaria is endemic in Senegal, with seasonal transmission, and the entire population is at risk. In recent years, high malaria incidence has been reported in urban and peri-urban areas of Senegal. An urban landscape analysis was conducted in three cities to identify the malaria transmission indicators and human behavior that may be driving the increasing malaria incidence occurring in urban environments. Specifically, mosquito vector bionomics and human sleeping behaviors including outdoor sleeping habits were assessed to guide the optimal deployment of targeted vector control interventions. METHODS: Longitudinal entomological monitoring using human landing catches and pyrethrum spray catches was conducted from May to December 2019 in Diourbel, Kaolack, and Touba, the most populous cities in Senegal after the capital Dakar. Additionally, a household survey was conducted in randomly selected houses and residential Koranic schools in the same cities to assess house structures, sleeping spaces, sleeping behavior, and population knowledge about malaria and vector control measures. RESULTS: Of the 8240 Anopheles mosquitoes collected from all the surveyed sites, 99.4% (8,191) were An. gambiae s.l., and predominantly An. arabiensis (99%). A higher number of An. gambiae s.l. were collected in Kaolack (77.7%, n = 6496) than in Diourbel and Touba. The overall mean human biting rate was 14.2 bites per person per night (b/p/n) and was higher outdoors (15.9 b/p/n) than indoors (12.5 b/p/n). The overall mean entomological inoculation rates ranged from 3.7 infectious bites per person per year (ib/p/y) in Diourbel to 40.2 ib/p/y in Kaolack. Low anthropophilic rates were recorded at all sites (average 35.7%). Of the 1202 households surveyed, about 24.3% of household members slept outdoors, except during the short rainy season between July and October, despite understanding how malaria is transmitted and the vector control measures used to prevent it. CONCLUSION: Anopheles arabiensis was the primary malaria vector in the three surveyed cities. The species showed an outdoor biting tendency, which represents a risk for the large proportion of the population sleeping outdoors. As all current vector control measures implemented in the country target endophilic vectors, these data highlight potential gaps in population protection and call for complementary tools and approaches targeting outdoor biting malaria vectors. |
Outbreak of locally acquired mosquito-transmitted (autochthonous) malaria - Florida and Texas, May-July 2023
Blackburn D , Drennon M , Broussard K , Morrison AM , Stanek D , Sarney E , Ferracci C , Huard S , Brennan W , Eaton J , Nealeigh S , Barber N , Zimler RA , Adams JN , Blackmore C , Gordillo M , Mercado R , Vore H , Scanlan K , Motie I , Stanfield L , Farooq A , Widel K , Tomson K , Kerr N , Nasir J , Cone M , Rice C , Larkin T , Hernandez E , Bencie J , Lesser CR , Dersch M , Ramirez-Lachmann S , Clark M , Rollo S , Bashadi A , Tyler R , Bolling B , Moore B , Sullivan B , Fonken E , Castillo R , Gonzalez Y , Olivares G , Mace KE , Sayre D , Lenhart A , Sutcliffe A , Dotson E , Corredor C , Rogers E , Raphael BH , Sapp SGH , Qvarnstrom Y , Ridpath AD , McElroy PD . MMWR Morb Mortal Wkly Rep 2023 72 (36) 973-978 Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States. |
Pragmatic selection of larval mosquito diets for insectary rearing of Anopheles gambiae and Aedes aegypti (preprint)
Benedict MQ , Hunt CM , Vella MG , Gonzalez KM , Dotson EM , Collins CM . bioRxiv 2019 740142 Larval mosquitoes are aquatic omnivorous scavengers which scrape food from submerged surfaces and collect suspended food particles with their mouth brushes. The composition of diets that have been used in insectaries varies widely though necessarily provides sufficient nutrition to allow colonies to be maintained. Issues such as cost, availability and experience influence which diet is selected. One component of larval diets, essential fatty acids, appears to be necessary for normal flight though deficiencies may not be evident in laboratory cages and are likely more important when mosquitoes are reared for release into the field in e.g. mark-release-recapture and genetic control activities.In this study, four diets were compared for rearing Anopheles gambiae and Aedes aegypti, all of which provide these essential fatty acids. Two diets were custom formulations specifically designed for mosquitoes (Damiens) and two were commercially available fish foods: Doctors Foster and Smith Koi Staple Diet and TetraMin Plus Flakes. Development rate, survival, dry weight and adult longevity of mosquitoes reared with these four diets were measured. The method of presentation of one diet, Koi pellets, was additionally fed in two forms, pellets or a slurry, to determine any effect of food presentation on survival and development rate.While various criteria might be selected to choose ‘the best’ food, the readily-available Koi pellets resulted in development rates and adult longevity equal to the other diets, high survival to the adult stage and, additionally, this is available at low cost. |
Anopheles adult anesthesia, feeding, and sex separation
Leite LN , Bascuñán P , Dotson EM , Benedict MQ . Cold Spring Harb Protoc 2023 The adult stage is the only nonaquatic stage of the Anopheles mosquito. Both male and female Anopheles mosquitoes require access to a source of sugar to survive. In the insectary, a temperature of ∼27°C and 80% relative humidity and a cycle of 12 h light:12 h dark light, ideally with a sunrise and sunset period, are necessary minimum conditions to mimic their natural environment. Laboratory-reared Anopheles can survive for over a month; however, decreased activity and increased mortality may be observed ∼2 wk postemergence depending on the species and health of the colony. Details on how to maintain adults Anopheles are discussed here. Information and considerations on blood and sugar feeding are described. This protocol also provides instructions on how to differentiate male and female adult mosquitoes. |
Anopheles larval rearing
Leite LN , Bascuñán P , Dotson EM , Benedict MQ . Cold Spring Harb Protoc 2023 Mosquito larvae are aquatic and go through four development stages (larval instars L1-L4) before pupation. Species vary in the duration of larval development, and a variety of external factors affect the development rate (e.g., water temperature, food type, and larval density), which are discussed more thoroughly elsewhere. Here, we detail how to rear Anopheles larvae. This protocol describes appropriate distribution of larvae into rearing pans, feeding of larvae, cleaning of pans, and care until pupation. |
Considerations for rearing and maintaining anopheles in the laboratory
Leite LN , Bascuñán P , Dotson EM , Benedict MQ . Cold Spring Harb Protoc 2023 Anopheles mosquitoes can transmit several human pathogens, including viruses such as o'nyong-nyong and parasites including Plasmodium spp. and Wuchereria spp., which cause malaria and filariasis, respectively. Rearing Anopheles species of medical importance under laboratory conditions allows researchers to carry out experiments to better understand their genetics, physiology, and behavior. However, Anopheles species vary in how easily they can be reared in the laboratory, and some species have been difficult to colonize. Once established, members of the important African Anopheles gambiae complex thrive following a standard protocol and are predictable in growth and development rates. Here, we provide useful basic information and guidance to successfully maintain colonies of A. gambiae and other species of Anopheles in a laboratory setting. We also provide an example of a 3-wk rearing schedule that produces sufficient numbers of mosquitoes while minimizing the work required during weekends. In the accompanying protocols, we detail efficient methods and techniques suitable for several species of this genus at the egg, larva, pupae, and adult stages; however, it will be necessary for researchers to adjust methods as needed based on site-specific rearing observations of their particular strains. |
Anopheles egg collection, disinfection, and hatching
Leite LN , Bascuñán P , Dotson EM , Benedict MQ . Cold Spring Harb Protoc 2023 Gravid (i.e., with fully developed eggs), mated Anopheles females typically lay their eggs directly on water ∼48-72 h after a blood meal. Unlike some other mosquito species, Anopheles eggs cannot be desiccated and stored for long durations, and, hence, colonies must be reared continuously. In this protocol, we discuss methods for egg collection, including individual and en masse oviposition; egg disinfection to avoid the transmission of infectious agents to the next generation; and egg hatching for colony maintenance or experimentation. We also include optional methods for estimating life history traits such as fecundity, fertility, and larval mortality rates from egg counts. |
Anopheles pupa collection and sex identification
Leite LN , Bascuñán P , Dotson EM , Benedict MQ . Cold Spring Harb Protoc 2023 For most Anopheles species, larval-pupal metamorphosis commences ∼1 wk after egg hatching. However, depending on the amount of food provided, H(2)O temperature, and larval density, the pupation process can be accelerated or delayed. Synchronous pupation is difficult to accomplish consistently, and, thus, pupae need to be separated from larvae daily. Adult emergence will take place 24-48 h after pupation. Most adults will eclose before the next morning (light cycle) in many species. Here, we provide information on some methods available to collect pupae and to sort pupae by sex. Notably, pupa collection and sorting are some of the most time-consuming procedures of the overall mosquito rearing process. Some methods mentioned here attempt to help reduce work effort and time required. |
Assessment of bio-based materials as a sustainable and scalable alternative for detection of plasmodium spp. (haemospororida: Plasmodiidae) sporozoites in field deployable testing
Gomez-Maldonado D , Stephens H , Sutcliffe AC , Camarano Eula MA , Vega Erramuspe IB , Dotson EM , Peresin MS , Zohdy S . J Med Entomol 2023 60 (3) 535-545 Malaria is responsible for over 435,000 deaths annually, mostly occurring in sub-Saharan Africa. Detecting Plasmodium spp. sporozoites (spzs) in the salivary glands of Anopheles (Diptera: Culicidae) vectors with circumsporozoite enzyme-linked immunosorbent assay (csELISA) is an important surveillance method. However, current technological advances are intellectual property and often require of distribution and highly trained users. The transition into paper-based rapid plataforms would allow for decentralization of survillance, especially in areas where it was virtually eliminated. The addition of bio-based materials have shown the potential to improve binding of target antigens, while being widely available. Here, we evaluate the use of chitosan and cellulose nanocrystals (CNC) as antibody carriers and substrate coatings on 96-well plates and on wax hydrophobized paper plates for the detection of Plasmodium falciparum (Pf), P. vivax VK210 (Pv210), and P. vivax VK247 (Pv247). To further improve the user-friendliness of the paper plates a quantitative photograph image-based color analysis was done. Interactions between the materials and the assay antibodies were studied by quartz crystal microbalance with dissipation monitoring (QCM-D). Overall, the addition of chitosan increased the interaction with antibodies and enhanced signaling in all tests. This work demonstrated that the adaptation of a PcsELISA shows potential as a cost-effective alternative assay platform easily adaptable in deployable testing sites that also showed reduction in reagent volumes by 80% and assay run time by seventh. While dipstick assays were previously developed, paper-based assays are a cost-effective and field-deployable alternative, reducing volumes of reagents that could be used in malaria control and elimination settings. |
Enhancing and leveraging the West Virginia's Prescription Drug Monitoring Program (PDMP) for public health surveillance and clinical decision making: A case study
Wood N , Mells J , Dotson T , Jeffries JE . J Public Health Manag Pract 2023 29 (2) E37-e43 West Virginia has struggled with an overdose epidemic for many years and continues to have the highest overdose death rate in the nation. However, through successful collaboration between the West Virginia Board of Pharmacy and the West Virginia Department of Health via its Violence and Injury Prevention Program, West Virginia has improved data quality, enhanced program development and implementation, and developed strategies to address the overdose epidemic. This multiagency collaboration plays an important role in addressing the overdose epidemic and promotes lasting interagency relationships. One strategy is overcoming barriers to maximizing and utilizing the Prescription Drug Monitoring Program, or PDMP. This strategy allows for a better understanding of a patient's prescription history and ensures safer prescribing practices. In addition, this strategic partnership facilitates the use of PDMP data for epidemiologic studies and public health surveillance, which results in sustainable analyses and dissemination of actionable data that are now driving public health action in West Virginia. |
Countrywide insecticide resistance monitoring and first report of the presence of the L1014S knock down resistance in Niger, West Africa
Soumaila H , Hamani B , Arzika II , Soumana A , Daouda A , Daouda FA , Iro SM , Gouro S , Zaman-Allah MS , Mahamadou I , Kadri S , Sal NM , Hounkanrin W , Mahamadou B , Zamaka HN , Labbo R , Laminou IM , Jackou H , Idrissa S , Coulibaly E , Bahari-Tohon Z , Mathieu E , Carlson J , Dotson E , Awolola TS , Flatley C , Chabi J . Malar J 2022 21 (1) 385 BACKGROUND: Mass distribution of insecticide-treated nets (ITNs) is the principal malaria vector control strategy adopted by Niger. To better inform on the most appropriate ITN to distribute, the National Malaria Control Programme (NMCP) of Niger and its partners, conducted insecticide resistance monitoring in selected sites across the country. METHODS: The susceptibility of Anopheles gambiae sensu lato (s.l.) to chlorfenapyr and pyrethroid insecticides was investigated in a total of sixteen sites in 2019 and 2020, using 2-5-day-old adults reared from wild collected larvae per site. The susceptibility status, pyrethroid resistance intensity at 5 and 10 times the diagnostic concentrations, and piperonyl butoxide (PBO) synergism with diagnostic concentrations of deltamethrin, permethrin and alpha-cypermethrin were assessed using WHO bioassays. Two doses (100 and 200g/bottle) of chlorfenapyr were tested using the CDC bottle assay method. Species composition and allele frequencies for knock-down resistance (kdr-L1014F and L1014S) and acetylcholinesterase (ace-1 G119S) mutations were further characterized using polymerase chain reaction (PCR). RESULTS: High resistance intensity to all pyrethroids tested was observed in all sites except for alpha-cypermethrin in Gaya and Tessaoua and permethrin in Gaya in 2019 recording moderate resistance intensity. Similarly, Balleyara, Keita and Tillabery yielded moderate resistance intensity for alpha-cypermethrin and deltamethrin, and Niamey V low resistance intensity against deltamethrin and permethrin in 2020. Pre-exposure to PBO substantially increased susceptibility with average increases in mortality between 0 and 70% for tested pyrethroids. Susceptibility to chlorfenapyr (100g/bottle) was recorded in all sites except in Tessaoua and Magaria where susceptibility was recorded at the dose of 200g/bottle. Anopheles coluzzii was the predominant malaria vector species in most of the sites followed by An. gambiae sensu stricto (s.s.) and Anopheles arabiensis. The kdr-L1014S allele, investigated for the first time, was detected in the country. Both kdr-L1014F (frequencies [0.46-0.81]) and L1014S (frequencies [0.41-0.87]) were present in all sites while the ace-1 G119S was between 0.08 and 0.20. CONCLUSION: The data collected will guide the NMCP in making evidence-based decisions to better adapt vector control strategies and insecticide resistance management in Niger, starting with mass distribution of new generation ITNs such as interceptor G2 and PBO ITNs. |
COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review.
Drzymalla E , Green RF , Knuth M , Khoury MJ , Dotson WD , Gundlapalli A . Clin Immunol 2022 243 109097 A better understanding of COVID-19 in people with primary immunodeficiency (PI), rare inherited defects in the immune system, is important for protecting this population, especially as population-wide approaches to mitigation change. COVID-19 outcomes in the PI population could have broader public health implications because some people with PI might be more likely to have extended illnesses, which could lead to increased transmission and emergence of variants. We performed a systematic review on COVID-19-associated morbidity and mortality in people with PI. Of the 1114 articles identified through the literature search, we included 68 articles in the review after removing 1046 articles because they were duplicates, did not involve COVID-19, did not involve PI, were not in English, were commentaries, or could not be accessed. The 68 articles included outcomes for 459 people with PI and COVID-19. Using data from these 459 people, we calculated a case fatality rate of 9%, hospitalization rate of 49%, and oxygen supplementation rate of 29%. Studies have indicated that a number of people with PI showed at least some immune response to COVID-19 vaccination, with responses varying by type of PI and other factors, although vaccine effectiveness against hospitalization was lower in the PI population than in the general population. In addition to being up-to-date on vaccinations, current strategies for optimizing protection for people with PI can include pre-exposure prophylaxis for those eligible and use of therapeutics. Overall, people with PI, when infected, tested positive and showed symptoms for similar lengths of time as the general population. However, a number of people with x-linked agammaglobulinemia (XLA) or other B-cell pathway defects were reported to have prolonged infections, measured by time from first positive SARS-CoV-2 test to first negative test. As prolonged infections might increase the likelihood of genetic variants emerging, SARS-CoV2 isolates from people with PI and extended illness would be good candidates to prioritize for whole genome sequencing. |
Evaluation of the residual efficacy and physical durability of five long-lasting insecticidal nets (LLINs) in Senegal
Diouf EH , Diouf M , Dieme C , Swamidoss I , Ngom EHM , Senghor MW , Mbaye M , Konaté A , Coulibaly Y , Tine D , Dia I , Dotson EM , Faye O , Konaté L . Malar J 2022 21 (1) 210 BACKGROUND: The preventive and curative strategies of malaria are based on promoting the use of long-lasting insecticidal nets (LLINs) and treating confirmed cases with artemisinin-based combination therapy. These strategies have led to a sharp decline in the burden of malaria, which remains a significant public health problem in sub-Saharan countries. The objective of this study was to determine and compare the residual efficacy of LLINs recommended by the World Health Organization. METHODS: The study was conducted in six villages in two sites in Senegal located in the Sahelo-Sudanian area of the Thiès region, 70 km from Dakar and in Mbagame, a semi-urban zone in the Senegal River Valley. A census was conducted of all sleeping places in each household to be covered by LLINs. Five brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN. RESULTS: A total of 3012 LLINs were distributed in 1249 households in both sites, with an average coverage rate of 94% (95% CI 92.68-95.3). After 36 months, the average retention rate was 12.5% and this rate was respectively 20.5%, 15.1%, 10%, 7%, and 3% for Olyset Net(®), Dawa Plus(®) 2.0, PermaNet(®) 2.0, NetProtect(®) and Life Net(®), respectively. The proportion of LLINs with holes and the average number of holes per mosquito net increased significantly during each follow-up, with a large predominance of size 1 (small) holes for all types of LLINs distributed. During the three-year follow-up, bioassay mortality rates of a susceptible strain of insectary reared Anopheles coluzzii decreased in the following net types: in Dawa Plus(®) 2.0 (100% to 51.7%), PermaNet(®) 2.0 (96.6% to 83%), and Olyset Net(®) (96.6% to 33.3%). Mortality rates remained at 100% in Life Net(®) over the same time period. After 36 months, the average insecticide content per brand of LLIN decreased by 40.9% for Dawa Plus(®) 2.0, 31% for PermaNet(®) 2.0, 39.6% for NetProtect(®) and 51.9% for Olyset Net(®) and 40.1% for Life Net. CONCLUSIONS: Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years. |
Health equity in the implementation of genomics and precision medicine: A public health imperative.
Khoury MJ , Bowen S , Dotson WD , Drzymalla E , Green RF , Goldstein R , Kolor K , Liburd LC , Sperling LS , Bunnell R . Genet Med 2022 24 (8) 1630-1639 Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade. |
Effective Oral RNA Interference (RNAi) Administration to Adult Anopheles gambiae Mosquitoes.
Taracena M , Hunt C , Pennington P , Andrew D , Jacobs-Lorena M , Dotson E , Wells M . J Vis Exp 2022 (181) RNA interference has been a heavily utilized tool for reverse genetic analysis for two decades. In adult mosquitoes, double-stranded RNA (dsRNA) administration has been accomplished primarily via injection, which requires significant time and is not suitable for field applications. To overcome these limitations, here we present a more efficient method for robust activation of RNAi by oral delivery of dsRNA to adult Anopheles gambiae. Long dsRNAs were produced in Escherichia coli strain HT115 (DE3), and a concentrated suspension of heat-killed dsRNA-containing bacteria in 10% sucrose was offered on cotton balls ad-libitum to adult mosquitoes. Cotton balls were replaced every 2 days for the duration of the treatment. Use of this method to target doublesex (a gene involved in sex differentiation) or fork head (which encodes a salivary gland transcription factor) resulted in reduced target gene expression and/or protein immunofluorescence signal, as measured by quantitative Real-Time PCR (qRT-PCR) or fluorescence confocal microscopy, respectively. Defects in salivary gland morphology were also observed. This highly flexible, user-friendly, low-cost, time-efficient method of dsRNA delivery could be broadly applicable to target genes important for insect vector physiology and beyond. |
Evidence supporting deployment of next generation insecticide treated nets in Burkina Faso: bioassays with either chlorfenapyr or piperonyl butoxide increase mortality of pyrethroid-resistant Anopheles gambiae
Hien AS , Soma DD , Maiga S , Coulibaly D , Diabaté A , Belemvire A , Diouf MB , Jacob D , Koné A , Dotson E , Awolola TS , Oxborough RM , Dabiré RK . Malar J 2021 20 (1) 406 BACKGROUND: Pyrethroid resistance poses a major threat to the efficacy of insecticide-treated nets (ITNs) in Burkina Faso and throughout sub-Saharan Africa, particularly where resistance is present at high intensity. For such areas, there are alternative ITNs available, including the synergist piperonyl butoxide (PBO)-based ITNs and dual active ingredient ITNs such as Interceptor G2 (treated with chlorfenapyr and alpha-cypermethrin). Before deploying alternative ITNs on a large scale it is crucial to characterize the resistance profiles of primary malaria vector species for evidence-based decision making. METHODS: Larvae from the predominant vector, Anopheles gambiae sensu lato (s.l.) were collected from 15 sites located throughout Burkina Faso and reared to adults for bioassays to assess insecticide resistance status. Resistance intensity assays were conducted using WHO tube tests to determine the level of resistance to pyrethroids commonly used on ITNs at 1×, 5 × and 10 × times the diagnostic dose. WHO tube tests were also used for PBO synergist bioassays with deltamethrin and permethrin. Bottle bioassays were conducted to determine susceptibility to chlorfenapyr at a dose of 100 µg/bottle. RESULTS: WHO tube tests revealed high intensity resistance in An. gambiae s.l. to deltamethrin and alpha-cypermethrin in all sites tested. Resistance intensity to permethrin was either moderate or high in 13 sites. PBO pre-exposure followed by deltamethrin restored full susceptibility in one site and partially restored susceptibility in all but one of the remaining sites (often reaching mortality greater than 80%). PBO pre-exposure followed by permethrin partially restored susceptibility in 12 sites. There was no significant increase in permethrin mortality after PBO pre-exposure in Kampti, Karangasso-Vigué or Mangodara; while in Seguenega, Orodara and Bobo-Dioulasso there was a significant increase in mortality, but rates remained below 50%. Susceptibility to chlorfenapyr was confirmed in 14 sites. CONCLUSION: High pyrethroid resistance intensity in An. gambiae s.l. is widespread across Burkina Faso and may be a predictor of reduced pyrethroid ITN effectiveness. PBO + deltamethrin ITNs would likely provide greater control than pyrethroid nets. However, since susceptibility in bioassays was not restored in most sites following pre-exposure to PBO, Interceptor G2 may be a better long-term solution as susceptibility was recorded to chlorfenapyr in nearly all sites. This study provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign. |
Investigation of Bacterial Infections Among Patients Treated With Umbilical Cord Blood-Derived Products Marketed as Stem Cell Therapies.
Hartnett KP , Powell KM , Rankin D , Gable P , Kim JJ , Spoto S , Breaker E , Hunter R , Dotson N , McAllister G , Stevens V , Halpin AL , Houston H , Epson E , Malarkey M , Mendoza M , McNeill L , Perkins KM . JAMA Netw Open 2021 4 (10) e2128615 IMPORTANCE: The number of clinics marketing stem cell products for joint diseases, chronic pain, and most recently, COVID-19, has increased despite warnings from the US Food and Drug Administration that stem cell products for these and other indications have not been proven safe or effective. OBJECTIVE: To examine bacterial infections in 20 patients who received umbilical cord blood-derived products marketed as stem cell treatment. DESIGN, SETTING, AND PARTICIPANTS: This case series is a national public health investigation including case-finding, medical record review and abstraction, and laboratory investigation, including sterility testing of products and whole-genome sequencing of patient and product isolates. Participants included patients who developed bacterial infections following administration of umbilical cord blood-derived products marketed as stem cell treatment during August 2017 to September 2018. Data analysis was performed from March 2019 to September 2021. EXPOSURES: Umbilical cord blood-derived products marketed as stem cell treatment. MAIN OUTCOMES AND MEASURES: Data were collected on patient infections and exposures. The Centers for Disease Control and Prevention performed sterility testing on undistributed and distributed vials of product marketed as stem cell treatment and performed whole-genome sequencing to compare patient and product bacterial isolates. RESULTS: Culture-confirmed bacterial infections were identified in 20 patients (median [range] age, 63 [2-89] years; 13 male patients [65%]) from 8 US states who sought stem cell treatment for conditions including pain, osteoarthritis, rheumatoid arthritis, and injury; all but 1 required hospitalization. The most frequently isolated bacteria from patients with infections were common enteric species, including Escherichia coli (14 patients) and Enterobacter cloacae (7 patients). Of unopened, undistributed products sampled for testing, 65% (22 of 34 vials) were contaminated with at least 1 of 16 bacterial species, mostly enteric. A patient isolate from Arizona matched isolates obtained from products administered to patients in Florida, and patient isolates from Texas matched undistributed product sent from the company in California. CONCLUSIONS AND RELEVANCE: Unapproved stem cell products can expose patients to serious risks without proven benefit. Sequencing results suggest a common source of extensive contamination, likely occurring during the processing of cord blood into product. Patients and health care practitioners who are considering the use of unapproved products marketed as stem cell treatment should be aware of their unproven benefits and potential risks, including serious infections. |
Adaptation of ELISA detection of Plasmodium falciparum and Plasmodium vivax circumsporozoite proteins in mosquitoes to a multiplex bead-based immunoassay
Sutcliffe AC , Irish SR , Rogier E , Finney M , Zohdy S , Dotson EM . Malar J 2021 20 (1) 377 BACKGROUND: Plasmodium spp. sporozoite rates in mosquitoes are used to better understand malaria transmission intensity, the relative importance of vector species and the impact of interventions. These rates are typically estimated using an enzyme-linked immunosorbent assay (ELISA) utilizing antibodies against the circumsporozoite protein of Plasmodium falciparum, Plasmodium vivax VK210 (P. vivax210) or P. vivax VK247 (P. vivax247), employing assays that were developed over three decades ago. The ELISA method requires a separate assay plate for each analyte tested and can be time consuming as well as requiring sample volumes not always available. The bead-based multiplex platform allows simultaneous measurement of multiple analytes and may improve the lower limit of detection for sporozoites. METHODS: Recombinant positive controls for P. falciparum, P. vivax210 and P. vivax247 and previously developed circumsporozoite (cs) ELISA antibodies were used to optimize conditions for the circumsporozoite multiplex bead assay (csMBA) and to determine the detection range of the csMBA. After optimizing assay conditions, known amounts of sporozoites were used to determine the lower limit of detection for the csELISA and csMBA and alternate cut-off measures were applied to demonstrate how cut-off criteria can impact lower limits of detection. Sporozoite rates from 1275 mosquitoes collected in Madagascar and 255 mosquitoes collected in Guinea were estimated and compared using the established csELISA and newly optimized csMBA. All mosquitoes were tested (initial test), and those that were positive were retested (retest). When sufficient sample volume remained, an aliquot of homogenate was boiled and retested (boiled retest), to denature any heat-unstable cross-reactive proteins. RESULTS: Following optimization of the csMBA, the lower limit of detection was 25 sporozoites per mosquito equivalent for P. falciparum, P. vivax210 and P. vivax247 whereas the lower limits of detection for csELISA were found to be 1400 sporozoites for P. falciparum, 425 for P. vivax210 and 1650 for P. vivax247. Combined sporozoite rates after re-testing of samples that initially tested positive for Madagascar mosquitoes by csELISA and csMBA were 1.4 and 10.3%, respectively, and for Guinea mosquitoes 2% by both assays. Boiling of samples followed by csMBA resulted in a decrease in the Madagascar sporozoite rate to 2.8-4.4% while the Guinea csMBA sporozoite rate remained at 2.0%. Using an alternative csMBA cut-off value of median fluorescence intensity (MFI) of 100 yielded a sporozoite rate after confirmational testing of 3.7% for Madagascar samples and 2.0% for Guinea samples. Whether using csMBA or csELISA, the following steps may help minimize false positives: specimens are appropriately stored and bisected anterior to the thorax-abdomen junction, aliquots of homogenate are boiled and retested following initial testing, and an appropriate cut-off value is determined. CONCLUSIONS: The csMBA is a cost-comparable and time saving alternative to the csELISA and may help eliminate false negatives due to a lower limit of detection, thus increasing sensitivity over the csELISA. The csMBA expands the potential analyses that can be done with a small volume of sample by allowing multiplex testing where analytes in addition to P. falciparum, P. vivax210 and P. vivax247 can be added following optimization. |
Delivery of Double-Stranded RNAs (dsRNAs) Produced by Escherichia coli HT115(DE3) for Nontransgenic RNAi-Based Insect Pest Management.
Taracena ML , GarciaCaffaro I , Paiva-Silva GO , Oliveira PL , Rendon PA , Dotson EM , Pennington PM . Methods Mol Biol 2022 2360 279-294 RNA interference (RNAi) is a powerful mechanism that can be exploited not only for physiology research but also for designing insect pest management approaches. Some insects cause harm by vectoring diseases dangerous to humans, livestock, or plants or by damaging crops. For at least a decade now, different insect control strategies that induce RNAi by delivering double stranded RNA (dsRNA) targeting essential genes have been proposed. Here, we focus on nontransgenic RNAi-based approaches that use oral delivery of dsRNA through feeding of inactivated bacteria to produce RNAi in disease vectors and in a crop pest. This potential pest management method could be easily adapted to target different genes or similar organisms. |
Gram-negative bacteria harboring multiple carbapenemase genes, United States, 2012-2019
Ham DC , Mahon G , Bhaurla SK , Horwich-Scholefield S , Klein L , Dotson N , Rasheed JK , McAllister G , Stanton RA , Karlsson M , Lonsway D , Huang JY , Brown AC , Walters MS . Emerg Infect Dis 2021 27 (9) 2475-2479 Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation. |
Cumulative Risks from Stressor Exposures and Personal Risk Factors in the Workplace: Examples from a Scoping Review.
Fox MA , Niemeier RT , Hudson N , Siegel MR , Dotson GS . Int J Environ Res Public Health 2021 18 (11) Protecting worker and public health involves an understanding of multiple determinants, including exposures to biological, chemical, or physical agents or stressors in combination with other determinants including type of employment, health status, and individual behaviors. This has been illustrated during the COVID-19 pandemic by increased exposure and health risks for essential workers and those with pre-existing conditions, and mask-wearing behavior. Health risk assessment practices for environmental and occupational health typically do not incorporate multiple stressors in combination with personal risk factors. While conceptual developments in cumulative risk assessment to inform a more holistic approach to these real-life conditions have progressed, gaps remain, and practical methods and applications are rare. This scoping review characterizes existing evidence of combined stressor exposures and personal factors and risk to foster methods for occupational cumulative risk assessment. The review found examples from many workplaces, such as manufacturing, offices, and health care; exposures to chemical, physical, and psychosocial stressors combined with modifiable and unmodifiable determinants of health; and outcomes including respiratory function and disease, cancers, cardio-metabolic diseases, and hearing loss, as well as increased fertility, menstrual dysfunction and worsened mental health. To protect workers, workplace exposures and modifiable and unmodifiable characteristics should be considered in risk assessment and management. Data on combination exposures can improve assessments and risk estimates and inform protective exposure limits and management strategies. |
From genes to public health: are we ready for DNA-based population screening?
Khoury MJ , Dotson WD . Genet Med 2021 23 (6) 996-998 The opinions expressed in the paper are those of the authors and do not necessarily reflect those of the Centers for Disease Control and Prevention. | | Recognizing the emerging role of genomics as a tool for population screening, the American College of Medical Genetics and Genomics (ACMG) has generated two companion guidance documents on DNA-based screening of healthy individuals that appear in the present issue of Genetics in Medicine.1,2 In this commentary, we offer a brief public health perspective on these documents in the context of recent work from the Centers for Disease Control and Prevention (CDC) Office of Genomics and Precision Public Health (OGPPH). |
Physiological responses to cryoprotectant treatment in an early larval stage of the malaria mosquito, Anopheles gambiae
Campbell JB , Dosch A , Hunt CM , Dotson EM , Benedict MQ , Rajamohan A , Rinehart JP . Cryobiology 2020 99 114-121 The development of cryopreservation protocols for Anopheles gambiae could significantly improve research and control efforts. Cryopreservation of any An. gambiae life stage has yet to be successful. The unique properties of embryos have proven to be resistant to any practical cryoprotectant loading. Therefore, we have chosen to investigate early non-feeding first instar larvae as a potential life stage for cryopreservation. In order to determine an appropriate cryoprotective compound, larvae were treated with progressively better glass-forming cryoprotective mixtures. Toxicity evaluation in combination with calorimetry-based water content and supercooling point depression assessments were used to determine the cryoprotectants that could be used for cryostorage of viable larvae. Approximately 35-75% of the larvae were viable after reasonably high osmotic and biochemical challenge. This study provides ample evidence for an active osmoregulatory response in the Anopheles larvae to counter the permeation of cryoprotectants from the surrounding medium. The data show a strong correlation between the larval mortality and water content, indicating an osmoregulatory crisis in the larva due to certain cryoprotectants such as the higher concentrations of ethane diol (ED). The observations also indicate that the ability of the larvae to regulate permeation and water balance ceases at or within 20 min of cryoprotectant exposure, but this is strongly influenced by the treatment temperature. Among the compound cryoprotectants tested, 25% ED + 10% dimethyl sulfoxide (DMSO) and 40% ED + 0.5 M trehalose seem to present a compromise between viability, larval water content, supercooling point depression, and glass forming abilities. |
Widespread zoophagy and detection of Plasmodium spp. in Anopheles mosquitoes in southeastern Madagascar.
Finney M , McKenzie BA , Rabaovola B , Sutcliffe A , Dotson E , Zohdy S . Malar J 2021 20 (1) 25 BACKGROUND: Malaria is a top cause of mortality on the island nation of Madagascar, where many rural communities rely on subsistence agriculture and livestock production. Understanding feeding behaviours of Anopheles in this landscape is crucial for optimizing malaria control and prevention strategies. Previous studies in southeastern Madagascar have shown that Anopheles mosquitoes are more frequently captured within 50 m of livestock. However, it remains unknown whether these mosquitoes preferentially feed on livestock. Here, mosquito blood meal sources and Plasmodium sporozoite rates were determined to evaluate patterns of feeding behaviour in Anopheles spp. and malaria transmission in southeastern Madagascar. METHODS: Across a habitat gradient in southeastern Madagascar 7762 female Anopheles spp. mosquitoes were collected. Of the captured mosquitoes, 492 were visibly blood fed and morphologically identifiable, and a direct enzyme-linked immunosorbent assay (ELISA) was used to test for swine, cattle, chicken, human, and dog blood among these specimens. Host species identification was confirmed for multiple blood meals using PCR along with Sanger sequencing. Additionally, 1,607 Anopheles spp. were screened for the presence of Plasmodium falciparum, P. vivax-210, and P. vivax 247 circumsporozoites (cs) by ELISA. RESULTS: Cattle and swine accounted, respectively, for 51% and 41% of all blood meals, with the remaining 8% split between domesticated animals and humans. Of the 1,607 Anopheles spp. screened for Plasmodium falciparum, Plasmodium vivax 210, and Plasmodium vivax 247 cs-protein, 45 tested positive, the most prevalent being P. vivax 247, followed by P. vivax 210 and P. falciparum. Both variants of P. vivax were observed in secondary vectors, including Anopheles squamosus/cydippis, Anopheles coustani, and unknown Anopheles spp. Furthermore, evidence of coinfection of P. falciparum and P. vivax 210 in Anopheles gambiae sensu lato (s.l.) was found. CONCLUSIONS: Here, feeding behaviour of Anopheles spp. mosquitoes in southeastern Madagascar was evaluated, in a livestock rich landscape. These findings suggest largely zoophagic feeding behaviors of Anopheles spp., including An. gambiae s.l. and presence of both P. vivax and P. falciparum sporozoites in Anopheles spp. A discordance between P. vivax reports in mosquitoes and humans exists, suggesting high prevalence of P. vivax circulating in vectors in the ecosystem despite low reports of clinical vivax malaria in humans in Madagascar. Vector surveillance of P. vivax may be relevant to malaria control and elimination efforts in Madagascar. At present, the high proportion of livestock blood meals in Madagascar may play a role in buffering (zooprophylaxis) or amplifying (zoopotentiation) the impacts of malaria. With malaria vector control efforts focused on indoor feeding behaviours, complementary approaches, such as endectocide-aided vector control in livestock may be an effective strategy for malaria reduction in Madagascar. |
Challenges and Opportunities for Communication about the Role of Genomics in Public Health.
Allen CG , Green RF , Bowen S , Dotson WD , Yu W , Khoury MJ . Public Health Genomics 2021 24 1-7 Despite growing awareness about the potential for genomic information to improve population health, lingering communication challenges remain in describing the role of genomics in public health programs. Identifying and addressing these challenges provide an important opportunity for appropriate communication to ensure the translation of genomic discoveries for public health benefits. In this commentary, we describe 5 common communication challenges encountered by the Centers for Disease Control and Prevention's Office of Genomics and Precision Public Health based on over 20 years of experience in the field. These include (1) communicating that using genomics to assess rare diseases can have an impact on public health; (2) providing evidence that genetic factors can add important information to environmental, behavioral, and social determinants of health; (3) communicating that although genetic factors are nonmodifiable, they can increase the impact of public health programs and communication strategies; (4) addressing the concern that genomics is not ready for clinical practice; and (5) communicating that genomics is valuable beyond the domain of health care and can be integrated as part of public health programs. We discuss opportunities for addressing these communication challenges and provide examples of ongoing approaches to communication about the role of genomics in public health to the public, researchers, and practitioners. |
Candida auris Outbreak in a COVID-19 Specialty Care Unit - Florida, July-August 2020.
Prestel C , Anderson E , Forsberg K , Lyman M , de Perio MA , Kuhar D , Edwards K , Rivera M , Shugart A , Walters M , Dotson NQ . MMWR Morb Mortal Wkly Rep 2021 70 (2) 56-57 In July 2020, the Florida Department of Health was alerted to three Candida auris bloodstream infections and one urinary tract infection in four patients with coronavirus disease 2019 (COVID-19) who received care in the same dedicated COVID-19 unit of an acute care hospital (hospital A). C. auris is a multidrug-resistant yeast that can cause invasive infection. Its ability to colonize patients asymptomatically and persist on surfaces has contributed to previous C. auris outbreaks in health care settings (1-7). Since the first C. auris case was identified in Florida in 2017, aggressive measures have been implemented to limit spread, including contact tracing and screening upon detection of a new case. Before the COVID-19 pandemic, hospital A conducted admission screening for C. auris and admitted colonized patients to a separate dedicated ward. |
Cryoprotectant toxicity and hypothermic sensitivity among Anopheles larvae.
Nesbitt JE , Swei A , Hunt C , Dotson E , Toner M , Sandlin RD . Cryobiology 2020 99 106-113 Laboratory rearing of mosquitoes is commonly practiced by researchers studying mosquito-borne infectious diseases and vector control methods. In the absence of cryopreservation methods to stabilize unique or genetically modified strains, mosquito lines must be continuously maintained, a laborious process that risks selection effects, contamination, and genetic drift. Towards the development of a cryopreservation protocol, a range of commonly used cryoprotectants were systematically characterized here both individually and as cocktails. Among first instar, feeding-stage An. gambiae and An. stephensi larvae, cryoprotectant toxicity followed the order of dimethyl sulfoxide > ethylene glycol > methanol. The resulting LD(50) values were used as the basis for the development of cryoprotectant cocktail solutions, where formulation optimization was streamlined using Taguchi methods of experimental design. Sensitivity to hypothermia was further evaluated to determine the feasibility of CPA loading at reduced temperatures and slow-cooling approaches to cryopreservation. The information described here contributes to the knowledge base necessary to inform the development of a cryopreservation protocol for Anopheles larvae. |
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