143 results on '"King, Christopher L."'
Search Results
2. Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers
- Author
-
Oyebanji, Oladayo A., Sundheimer, Nicholas, Ragavapuram, Vaishnavi, Wilson, Brigid M., Abul, Yasin, Gravenstein, Stefan, Bosch, Jürgen, King, Christopher L., and Canaday, David H.
- Published
- 2024
- Full Text
- View/download PDF
3. Higher outdoor mosquito density and Plasmodium infection rates in and around malaria index case households in low transmission settings of Ethiopia: Implications for vector control
- Author
-
Abossie, Ashenafi, Demissew, Assalif, Getachew, Hallelujah, Tsegaye, Arega, Degefa, Teshome, Habtamu, Kassahun, Zhong, Daibin, Wang, Xiaoming, Lee, Ming-Chieh, Zhou, Guofa, King, Christopher L, Kazura, James W, Yan, Guiyun, and Yewhalaw, Delenasaw
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Microbiology ,Clinical Sciences ,Medical Microbiology ,Infectious Diseases ,Malaria ,Prevention ,Vector-Borne Diseases ,Rare Diseases ,2.2 Factors relating to the physical environment ,Aetiology ,3.2 Interventions to alter physical and biological environmental risks ,Prevention of disease and conditions ,and promotion of well-being ,Infection ,Good Health and Well Being ,Animals ,Cattle ,Humans ,Mosquito Vectors ,Ethiopia ,Feeding Behavior ,Anopheles ,Sporozoites ,Mosquito Control ,Index case ,Reactive case detection ,Sporozoite rate ,Residual malaria ,Public Health and Health Services ,Mycology & Parasitology ,Tropical Medicine ,Medical microbiology - Abstract
BackgroundUnderstanding the clustering of infections for persistent malaria transmission is critical to determining how and where to target specific interventions. This study aimed to determine the density, blood meal sources and malaria transmission risk of anopheline vectors by targeting malaria index cases, their neighboring households and control villages in Arjo-Didessa, southwestern Ethiopia.MethodsAn entomological study was conducted concurrently with a reactive case detection (RCD) study from November 2019 to October 2021 in Arjo Didessa and the surrounding vicinity, southwestern Ethiopia. Anopheline mosquitoes were collected indoors and outdoors in index case households and their surrounding households (neighboring households), as well as in control households, using pyrethrum spray cache (PSC) and U.S. Centers for Disease Control and Prevention (CDC) light traps. Adult mosquitoes were morphologically identified, and speciation in the Anopheles gambiae complex was done by PCR. Mosquito Plasmodium infections and host blood meal sources were detected by circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA) and cytochrome b-based blood meal PCR, respectively.ResultsAmong the 770 anopheline mosquitoes collected, An. gambiae sensu lato (A. gambiae s.l.) was the predominant species, accounting for 87.1% (n = 671/770) of the catch, followed by the Anopheles coustani complex and Anopheles pharoensis, which accounted for 12.6% (n = 97/770) and 0.26% (n = 2/770) of the catch, respectively. From the sub-samples of An. gambiae s.l.analyzed with PCR, An. arabiensis and Anopheles amharicus were identified. The overall mean density of mosquitoes was 1.26 mosquitoes per trap per night using the CDC light traps. Outdoor mosquito density was significantly higher than indoor mosquito density in the index and neighboring households (P = 0.0001). The human blood index (HBI) and bovine blood index (BBI) of An. arabiensis were 20.8% (n = 34/168) and 24.0% (n = 41/168), respectively. The overall Plasmodium sporozoite infection rate of anophelines (An. arabiensis and An. coustani complex) was 4.4% (n = 34/770). Sporozoites were detected indoors and outdoors in captured anopheline mosquitoes. Of these CSP-positive species for Pv-210, Pv-247 and Pf, 41.1% (n = 14/34) were captured outdoors. A significantly higher proportion of sporozoite-infected mosquitoes were caught in index case households (5.6%, n = 8/141) compared to control households (1.1%, n = 2/181) (P = 0.02), and in neighboring households (5.3%, n = 24/448) compared to control households (P = 0.01).ConclusionsThe findings of this study indicated that malaria index cases and their neighboring households had higher outdoor mosquito densities and Plasmodium infection rates. The study also highlighted a relatively higher outdoor mosquito density, which could increase the potential risk of outdoor malaria transmission and may play a role in residual malaria transmission. Thus, it is important to strengthen the implementation of vector control interventions, such as targeted indoor residual spraying, long-lasting insecticidal nets and other supplementary vector control measures such as larval source management and community engagement approaches. Furthermore, in low transmission settings, such as the Arjo Didessa Sugarcane Plantation, providing health education to local communities, enhanced environmental management and entomological surveillance, along with case detection and management by targeting of malaria index cases and their immediate neighboring households, could be important measures to control residual malaria transmission and achieve the targeted elimination goals.
- Published
- 2024
4. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection
- Author
-
Ahuja, Sunil K, Manoharan, Muthu Saravanan, Lee, Grace C, McKinnon, Lyle R, Meunier, Justin A, Steri, Maristella, Harper, Nathan, Fiorillo, Edoardo, Smith, Alisha M, Restrepo, Marcos I, Branum, Anne P, Bottomley, Matthew J, Orrù, Valeria, Jimenez, Fabio, Carrillo, Andrew, Pandranki, Lavanya, Winter, Caitlyn A, Winter, Lauryn A, Gaitan, Alvaro A, Moreira, Alvaro G, Walter, Elizabeth A, Silvestri, Guido, King, Christopher L, Zheng, Yong-Tang, Zheng, Hong-Yi, Kimani, Joshua, Blake Ball, T, Plummer, Francis A, Fowke, Keith R, Harden, Paul N, Wood, Kathryn J, Ferris, Martin T, Lund, Jennifer M, Heise, Mark T, Garrett, Nigel, Canady, Kristen R, Abdool Karim, Salim S, Little, Susan J, Gianella, Sara, Smith, Davey M, Letendre, Scott, Richman, Douglas D, Cucca, Francesco, Trinh, Hanh, Sanchez-Reilly, Sandra, Hecht, Joan M, Cadena Zuluaga, Jose A, Anzueto, Antonio, Pugh, Jacqueline A, Agan, Brian K, Root-Bernstein, Robert, Clark, Robert A, Okulicz, Jason F, and He, Weijing
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Biodefense ,Infectious Diseases ,Aging ,Vaccine Related ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Female ,Humans ,Longevity ,COVID-19 ,Inflammation ,Outcome Assessment ,Health Care ,South Texas Veterans Health Care System COVID-19 team - Abstract
Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.
- Published
- 2023
5. Enhancing Malaria Research, Surveillance, and Control in Endemic Areas of Kenya and Ethiopia
- Author
-
Githure, John I, Yewhalaw, Delenasaw, Atieli, Harrysone, Hemming-Schroeder, Elizabeth, Lee, Ming-Chieh, Wang, Xiaoming, Zhou, Guofa, Zhong, Daibin, King, Christopher L, Dent, Arlene, Mukabana, Wolfgang Richard, Degefa, Teshome, Hsu, Kuolin, Githeko, Andrew K, Okomo, Gordon, Dayo, Lilyana, Tushune, Kora, Omondi, Charles O, Taffese, Hiwot S, Kazura, James W, and Yan, Guiyun
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Prevention ,Infectious Diseases ,Vector-Borne Diseases ,Malaria ,Clinical Research ,2.4 Surveillance and distribution ,3.2 Interventions to alter physical and biological environmental risks ,Prevention of disease and conditions ,and promotion of well-being ,Aetiology ,Infection ,Good Health and Well Being ,Animals ,Ethiopia ,Humans ,Kenya ,Malaria ,Vivax ,Mosquito Control ,Mosquito Vectors ,Medical and Health Sciences ,Tropical Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
Malaria control programs in Africa encounter daunting challenges that hinder progressive steps toward elimination of the disease. These challenges include widespread insecticide resistance in mosquito vectors, increasing outdoor malaria transmission, lack of vector surveillance and control tools suitable for outdoor biting vectors, weakness in malaria surveillance, and an inadequate number of skilled healthcare personnel. Ecological and epidemiological changes induced by environmental modifications resulting from water resource development projects pose additional barriers to malaria control. Cognizant of these challenges, our International Center of Excellence for Malaria Research (ICEMR) works in close collaboration with relevant government ministries and agencies to align its research efforts with the objectives and strategies of the national malaria control and elimination programs for the benefit of local communities. Our overall goal is to assess the impact of water resource development projects, shifting agricultural practices, and vector interventions on Plasmodium falciparum and P. vivax malaria in Kenya and Ethiopia. From 2017 to date, the ICEMR has advanced knowledge of malaria epidemiology, transmission, immunology, and pathogenesis, and developed tools to enhance vector surveillance and control, improved clinical malaria surveillance and diagnostic methods, and strengthened the capacity of local healthcare providers. Research findings from the ICEMR will inform health policy and strategic planning by ministries of health in their quest to sustain malaria control and achieve elimination goals.
- Published
- 2022
6. Impact of Environmental Modifications on the Ecology, Epidemiology, and Pathogenesis of Plasmodium falciparum and Plasmodium vivax Malaria in East Africa
- Author
-
Yan, Guiyun, Lee, Ming-Chieh, Zhou, Guofa, Jiang, Ai-Ling, Degefa, Teshome, Zhong, Daibin, Wang, Xiaoming, Hemming-Schroeder, Elizabeth, Mukabana, Wolfgang R, Dent, Arlene E, King, Christopher L, Hsu, Kuolin, Beeson, James, Githure, John I, Atieli, Harrysone, Githeko, Andrew K, Yewhalaw, Delenasaw, and Kazura, James W
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Infectious Diseases ,Malaria ,Vector-Borne Diseases ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Zero Hunger ,Africa ,Eastern ,Animals ,Anopheles ,Ethiopia ,Humans ,Larva ,Malaria ,Falciparum ,Malaria ,Vivax ,Mosquito Vectors ,Plasmodium falciparum ,Plasmodium vivax ,Water ,Medical and Health Sciences ,Tropical Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
Food insecurity, recurrent famine, and poverty threaten the health of millions of African residents. Construction of dams and rural irrigation schemes is key to solving these problems. The sub-Saharan Africa International Center of Excellence for Malaria Research addresses major knowledge gaps and challenges in Plasmodium falciparum and Plasmodium vivax malaria control and elimination in malaria-endemic areas of Kenya and Ethiopia where major investments in water resource development are taking place. This article highlights progress of the International Center of Excellence for Malaria Research in malaria vector ecology and behavior, epidemiology, and pathogenesis since its inception in 2017. Studies conducted in four field sites in Kenya and Ethiopia show that dams and irrigation increased the abundance, stability, and productivity of larval habitats, resulting in increased malaria transmission and a greater disease burden. These field studies, together with hydrological and malaria transmission modeling, enhance the ability to predict the impact of water resource development projects on vector larval ecology and malaria risks, thereby facilitating the development of optimal water and environmental management practices in the context of malaria control efforts. Intersectoral collaborations and community engagement are crucial to develop and implement cost-effective malaria control strategies that meet food security needs while controlling malaria burden in local communities.
- Published
- 2022
7. The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization
- Author
-
Karger, Amy B, Brien, James D, Christen, Jayne M, Dhakal, Santosh, Kemp, Troy J, Klein, Sabra L, Pinto, Ligia A, Premkumar, Lakshmanane, Roback, John D, Binder, Raquel A, Boehme, Karl W, Boppana, Suresh, Cordon-Cardo, Carlos, Crawford, James M, Daiss, John L, Dupuis, Alan P, Espino, Ana M, Firpo-Betancourt, Adolfo, Forconi, Catherine, Forrest, J Craig, Girardin, Roxie C, Granger, Douglas A, Granger, Steve W, Haddad, Natalie S, Heaney, Christopher D, Hunt, Danielle T, Kennedy, Joshua L, King, Christopher L, Krammer, Florian, Kruczynski, Kate, LaBaer, Joshua, Lee, F Eun-Hyung, Lee, William T, Liu, Shan-Lu, Lozanski, Gerard, Lucas, Todd, Mendu, Damodara Rao, Moormann, Ann M, Murugan, Vel, Okoye, Nkemakonam C, Pantoja, Petraleigh, Payne, Anne F, Park, Jin, Pinninti, Swetha, Pinto, Amelia K, Pisanic, Nora, Qiu, Ji, Sariol, Carlos A, Simon, Viviana, Song, Lusheng, Steffen, Tara L, Stone, E Taylor, Styer, Linda M, Suthar, Mehul S, Thomas, Stefani N, Thyagarajan, Bharat, Wajnberg, Ania, Yates, Jennifer L, and Sobhani, Kimia
- Subjects
Clinical Research ,Cancer ,Emerging Infectious Diseases ,Good Health and Well Being ,Antibodies ,Viral ,COVID-19 ,COVID-19 Testing ,Humans ,SARS-CoV-2 ,Serologic Tests ,SeroNet ,assay harmonization ,serology ,Immunology ,Microbiology - Abstract
In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.
- Published
- 2022
8. Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination
- Author
-
Gravenstein, Stefan, DeVone, Frank, Oyebanji, Oladayo A., Abul, Yasin, Cao, Yi, Chan, Philip A., Halladay, Christopher W., Rudolph, James L., Nugent, Clare, Bosch, Jürgen, King, Christopher L., Wilson, Brigid M., Balazs, Alejandro B., White, Elizabeth M., Canaday, David H., and McConeghy, Kevin W.
- Published
- 2024
- Full Text
- View/download PDF
9. Human monoclonal antibodies inhibit invasion of transgenic Plasmodium knowlesi expressing Plasmodium vivax Duffy binding protein
- Author
-
Watson, Quentin D., Carias, Lenore L., Malachin, Alyssa, Redinger, Karli R., Bosch, Jürgen, Bardelli, Martino, Baldor, Lea, Feufack-Donfack, Lionel Brice, Popovici, Jean, Moon, Robert W., Draper, Simon J., Zimmerman, Peter A., and King, Christopher L.
- Published
- 2023
- Full Text
- View/download PDF
10. Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis
- Author
-
van Eijk, Anna Maria, Stepniewska, Kasia, Hill, Jenny, Taylor, Steve M., Rogerson, Stephen J., Cottrell, Gilles, Chico, R. Matthew, Gutman, Julie R., Tinto, Hallidou, Unger, Holger W., Yanow, Stephanie K., Accrombessi, Manfred, Adegnika, Ayola A., Ahmed, Rukhsana, Arango-Flórez, Eliana María, Arevalo-Herrera, Myriam, Arinaitwe, Emmanual, Arnaldo, Paulo, Ashorn, Per, Ashorn, Ulla, Bardaji, Azucena, Betuela, Inoni, Bharti, Praveen K., Bohissou, Francis, Bôtto-Menezes, Camila, Braun, Vera, Briand, Valerie, Briggs, Jessica, Castellanos, María Eugenia, Chandramohan, Daniel, Chaponda, Enesia Banda, Chitnis, Chetan, Cohee, Lauren M., Cot, Michel, d'Alessandro, Umberto, Denoeud-Ndam, Lise, Desai, Meghna, Dicko, Alassane, Ding, Xavier, Dorsey, Grant, Duffy, Patrick E., Elbadry, Maha A., Enosse, Sonia M., Fan, Yue, Fievet, Nadine, Fried, Michal, Genton, Blaise, Gonzalez, Raquel, Greenwood, Brian, Kalilani, Linda, Kattenberg, Johanna H., Kayentao, Kassoum, Khairallah, Carole, King, Christopher L., Kochar, Dhanpat Kumar, Kochar, Swati, Koukouikila-Koussounda, Felix, Landis, Sarah H., Laufer, Miriam K., Leke, Rose F., Macete, Eusebio, Maculuve, Sonia, Madanitsa, Mwayiwawo, Mahamar, Almahamoudou, Maleta, Ken, Malhotra, Indu, Zoleko Manego, Rella, Martinez-Espinosa, Flor Ernestina, Massougbodji, Achille, Mathanga, Don, Menegon, Michela, Menendez, Clara, Mens, Petra, Meremikwu, Martin, Mockenhaupt, Frank P., Mombo-Ngoma, Ghyslain, Mosha, Dominic, Mueller, Ivo, Nahum, Alain, Natureeba, Paul, Ndam, Nicaise, Ntoumi, Francine, Oduwole, Olabisi A., Okech, Bernard A., Ome-Kaius, Maria, Otieno, Kephas, Padilla, Norma, Ramharter, Michal, Rochford, Rosemary, Rosanas-Urgell, Anna, Ruperez, Maria, Sabourin, Katherine R., Sanz, Sergi, Schallig, Henk D., Scott, Susana, Sevene, Esperanca, Severini, Carlo, Tagbor, Harry, Taylor, Diane Wallace, Traore Coulibaly, Maminata, Vasquez, Ana, Walker-Abbey, Annie, Wylie, Blair J., Zannou, Djimon M., Meshnick, Stephen R., ter Kuile, Feiko O., Mayor, Alfredo, Taylor, Steve M, Rogerson, Stephen J, Chico, R Matthew, Gutman, Julie R, Tinto, Halidou, Unger, Holger W, Yanow, Stephanie K, Meshnick, Steven R, and ter Kuile, Feiko O
- Published
- 2023
- Full Text
- View/download PDF
11. Non-invasive Thermal Imaging for Estimation of the Fecundity of Live Female Onchocerca Worms
- Author
-
Dedhiya, Ronak, Kakileti, Siva Teja, Gopinath, Kanchana, Edem, Agbogah, Donkor, Bismark, Seidu, Abdulai Mahmood, Attah, Simon K., King, Christopher L., Opoku, Nicholas, Manjunath, Geetha, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Kakileti, Siva Teja, editor, Gabrani, Maria, editor, Manjunath, Geetha, editor, Rosen-Zvi, Michal, editor, Braman, Nathaniel, editor, Schwartz, Robert G., editor, Frangi, Alejandro F., editor, Chung, Pau-Choo, editor, Weight, Christopher, editor, and Jagadish, Vekataraman, editor
- Published
- 2022
- Full Text
- View/download PDF
12. Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine
- Author
-
Dudley, Holly M., O'Mara, Megan, Auma, Ann, Gong, Jenny, Ross, Yael, Gurevich, Natalie, Carbone, Sarah, Reihs, Alex, Nguyen, Ynez, McComsey, Grace A., Cao, Yi, Balazs, Alejandro B., Gordesky, Larraine, Payne, Michael, Singer, Nora, Kostadinova, Lenche, Wilson, Brigid, Zidar, David A., King, Christopher L., Canaday, David H., Shive, Carey L., Mattar, Maya M., and Anthony, Donald D.
- Published
- 2023
- Full Text
- View/download PDF
13. Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial
- Author
-
Laman, Moses, Tavul, Livingstone, Karl, Stephan, Kotty, Bethuel, Kerry, Zebede, Kumai, Stephen, Samuel, Anna, Lorry, Lina, Timinao, Lincoln, Howard, S Cade, Makita, Leo, John, Lucy, Bieb, Sibauk, Wangi, James, Albert, Jeffrey M, Payne, Michael, Weil, Gary J, Tisch, Daniel J, Bjerum, Catherine M, Robinson, Leanne J, and King, Christopher L
- Published
- 2022
- Full Text
- View/download PDF
14. Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents?
- Author
-
Oyebanji, Oladayo A., Wilson, Brigid, Keresztesy, Debbie, Carias, Lenore, Wilk, Dennis, Payne, Michael, Aung, Htin, Denis, Kerri St., Lam, Evan C., Rowley, Christopher F., Berry, Sarah D., Cameron, Cheryl M., Cameron, Mark J., Schmader, Kenneth E., Balazs, Alejandro B., King, Christopher L., Canaday, David H., and Gravenstein, Stefan
- Published
- 2021
- Full Text
- View/download PDF
15. The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study
- Author
-
Habtamu, Kassahun, primary, Getachew, Hallelujah, additional, Abossie, Ashenafi, additional, Demissew, Assalif, additional, Tsegaye, Arega, additional, Degefa, Teshome, additional, Wang, Xiaoming, additional, Lee, Ming-Chieh, additional, Zhou, Guofa, additional, Kibret, Solomon, additional, King, Christopher L., additional, Kazura, James W., additional, Petros, Beyene, additional, Yewhalaw, Delenasaw, additional, and Yan, Guiyun, additional
- Published
- 2024
- Full Text
- View/download PDF
16. Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages
- Author
-
Winnicki, Anna C., primary, Dietrich, Melanie H., additional, Yeoh, Lee M., additional, Carias, Lenore L., additional, Roobsoong, Wanlapa, additional, Drago, Chiara L., additional, Malachin, Alyssa N., additional, Redinger, Karli R., additional, Feufack-Donfack, Lionel Brice, additional, Baldor, Lea, additional, Jung, Nicolai C., additional, McLaine, Olivia S., additional, Skomorovska-Prokvolit, Yelenna, additional, Orban, Agnes, additional, Opi, D. Herbert, additional, Sattabongkot, Jetsumon, additional, Tham, Wai-Hong, additional, Popovici, Jean, additional, Beeson, James G., additional, Bosch, Jürgen, additional, and King, Christopher L., additional
- Published
- 2024
- Full Text
- View/download PDF
17. Non-invasive Thermal Imaging for Estimation of the Fecundity of Live Female Onchocerca Worms
- Author
-
Dedhiya, Ronak, primary, Kakileti, Siva Teja, additional, Gopinath, Kanchana, additional, Edem, Agbogah, additional, Donkor, Bismark, additional, Seidu, Abdulai Mahmood, additional, Attah, Simon K., additional, King, Christopher L., additional, Opoku, Nicholas, additional, and Manjunath, Geetha, additional
- Published
- 2022
- Full Text
- View/download PDF
18. The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on haemoglobin levels in Ethiopia: a longitudinal cohort study.
- Author
-
Habtamu, Kassahun, Getachew, Hallelujah, Abossie, Ashenafi, Demissew, Assalif, Tsegaye, Arega, Degefa, Teshome, Wang, Xiaoming, Lee, Ming-Chieh, Zhou, Guofa, Kibret, Solomon, King, Christopher L., Kazura, James W., Petros, Beyene, Yewhalaw, Delenasaw, and Yan, Guiyun
- Subjects
PLASMODIUM falciparum ,MALARIA ,GLUCOSE-6-phosphate dehydrogenase deficiency ,HEMOGLOBINS ,GLUCOSE-6-phosphate dehydrogenase ,PRIMAQUINE - Abstract
Background: To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28–15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to − 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (− 0.60 g/dL) than in the G6PDd ACT alone group (− 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = − 0.00 to 0.20) and 0.05 g/dl (95% CI = − 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions: This study's findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. Duffy antigen is expressed during erythropoiesis in Duffy-negative individuals
- Author
-
Dechavanne, Celia, primary, Dechavanne, Sebastien, additional, Bosch, Jürgen, additional, Metral, Sylvain, additional, Redinger, Karli R., additional, Watson, Quentin D., additional, Ratsimbasoa, Arsene C., additional, Roeper, Brooke, additional, Krishnan, Sushma, additional, Fong, Rich, additional, Bennett, Seth, additional, Carias, Lenore, additional, Chen, Edwin, additional, Salinas, Nichole D., additional, Ghosh, Anil, additional, Tolia, Niraj H., additional, Woost, Philip G., additional, Jacobberger, James W., additional, Colin, Yves, additional, Gamain, Benoit, additional, King, Christopher L., additional, and Zimmerman, Peter A., additional
- Published
- 2023
- Full Text
- View/download PDF
20. Naturally acquired blocking human monoclonal antibodies to Plasmodiumvivax reticulocyte binding protein 2b
- Author
-
Chan, Li-Jin, Gandhirajan, Anugraha, Carias, Lenore L., Dietrich, Melanie H., Vadas, Oscar, Visentin, Remy, França, Camila T., Menant, Sebastien, Soldati-Favre, Dominique, Mueller, Ivo, King, Christopher L., and Tham, Wai-Hong
- Published
- 2021
- Full Text
- View/download PDF
21. Safety and tolerability of moxidectin and ivermectin combination treatments for lymphatic filariasis in Côte d’Ivoire: A randomized controlled superiority study
- Author
-
Bjerum, Catherine M., primary, Koudou, Benjamin G., additional, Ouattara, Allassane F., additional, Lew, Daphne, additional, Goss, Charles W., additional, Gabo, Pascal T., additional, King, Christopher L., additional, Fischer, Peter U., additional, Weil, Gary J., additional, and Budge, Philip J., additional
- Published
- 2023
- Full Text
- View/download PDF
22. Pharmacokinetics of Moxidectin combined with Albendazole or Albendazole plus Diethylcarbamazine for Bancroftian Filariasis
- Author
-
Chhonker, Yashpal S., primary, Bjerum, Catherine, additional, Bala, Veenu, additional, Ouattara, Allassane F., additional, Koudou, Benjamin G., additional, Gabo, Toki P., additional, Alshehri, Abdullah, additional, Meïté, Abdoulaye, additional, Fischer, Peter U., additional, Weil, Gary J., additional, King, Christopher L., additional, Budge, Philip J., additional, and Murry, Daryl J., additional
- Published
- 2023
- Full Text
- View/download PDF
23. Neutralization and binding antibody response to second bivalent COVID‐19 vaccination in nursing home residents
- Author
-
Oyebanji, Oladayo A., primary, Abul, Yasin, additional, Wilson, Brigid M., additional, Bosch, Jurgen, additional, Didion, Elise M., additional, Paxitzis, Alexandra N., additional, Sundheimer, Nicholas, additional, Ragavapuram, Vaishnavi, additional, Wilk, Dennis, additional, Keresztesy, Debbie, additional, Aung, Htin, additional, Cao, Yi, additional, King, Christopher L., additional, Balazs, Alejandro B., additional, White, Elizabeth M., additional, Gravenstein, Stefan, additional, and Canaday, David H., additional
- Published
- 2023
- Full Text
- View/download PDF
24. SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine--Ohio and Rhode Island, September-November 2022
- Author
-
Canaday, David H., Oyebanji, Oladayo A., White, Elizabeth M., Bosch, Jurgen, Nugent, Clare, Vishnepolskiy, Igor, Abul, Yasin, Didion, Elise M., Paxitzis, Alexandra, Sundheimer, Nicholas, Ragavapuram, Vaishnavi, Wilk, Dennis, Keresztesy, Debbie, Cao, Yi, St. Denis, Kerri, McConeghy, Kevin W., McDonald, L. Clifford, Jernigan, John A., Mylonakis, Eleftherios, Wilson, Brigid M., King, Christopher L., Balazs, Alejandro B., and Gravenstein, Stefan
- Subjects
Infection -- Health aspects ,RNA -- Health aspects ,Vaccines -- Health aspects ,Nursing homes -- Health aspects ,Health - Abstract
Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19--related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the [...]
- Published
- 2023
25. Community control strategies for scabies: A cluster randomised noninferiority trial
- Author
-
Hardy, Myra, Samuela, Josaia, Kama, Mike, Tuicakau, Meciusela, Romani, Lucia, Whitfeld, Margot J., King, Christopher L., Weil, Gary J., Schuster, Tibor, Grobler, Anneke C., Engelman, Daniel, Robinson, Leanne J., Kaldor, John M., and Steer, Andrew C.
- Subjects
Infection control -- Methods ,Ivermectin -- Dosage and administration ,Scabies -- Drug therapy ,Community health services -- Methods ,Biological sciences - Abstract
Background Scabies is a neglected tropical disease hyperendemic to many low- and middle-income countries. Scabies can be successfully controlled using mass drug administration (MDA) using 2 doses of ivermectin-based treatment. If effective, a strategy of 1-dose ivermectin-based MDA would have substantial advantages for implementing MDA for scabies at large scale. Methods and findings We did a cluster randomised, noninferiority, open-label, 3-group unblinded study comparing the effectiveness of control strategies on community prevalence of scabies at 12 months. All residents from 35 villages on 2 Fijian islands were eligible to participate. Villages were randomised 1:1:1 to 2-dose ivermectin-based MDA (IVM-2), 1-dose ivermectin-based MDA (IVM-1), or screen and treat with topical permethrin 5% for individuals with scabies and their household contacts (SAT). All groups also received diethylcarbamazine and albendazole for lymphatic filariasis control. For IVM-2 and IVM-1, oral ivermectin was dosed at 200 [mu]g/kg and when contraindicated substituted with permethrin. We designated a noninferiority margin of 5%. We enrolled 3,812 participants at baseline (July to November 2017) from the 35 villages with median village size of 108 (range 18 to 298). Age and sex of participants were representative of the population with 51.6% male and median age of 25 years (interquartile range 10 to 47). We enrolled 3,898 at 12 months (July to November 2018). At baseline, scabies prevalence was similar in all groups: IVM-2: 11.7% (95% confidence interval (CI) 8.5 to 16.0); IVM-1: 15.2% (95% CI 9.4 to 23.8); SAT: 13.6% (95% CI 7.9 to 22.4). At 12 months, scabies decreased substantially in all groups: IVM-2: 1.3% (95% CI 0.6 to 2.5); IVM-1: 2.7% (95% CI 1.1 to 6.5); SAT: 1.1% (95% CI 0.6 to 2.0). The risk difference in scabies prevalence at 12 months between the IVM-1 and IVM-2 groups was 1.2% (95% CI -0.2 to 2.7, p = 0.10). Limitations of the study included the method of scabies diagnosis by nonexperts, a lower baseline prevalence than anticipated, and the addition of diethylcarbamazine and albendazole to scabies treatment. Conclusions All 3 strategies substantially reduced prevalence. One-dose was noninferior to 2-dose ivermectin-based MDA, as was a screen and treat approach, for community control of scabies. Further trials comparing these approaches in varied settings are warranted to inform global scabies control strategies. Trial registration Clinitrials.gov NCT03177993 and ANZCTR N12617000738325., Author(s): Myra Hardy 1,2, Josaia Samuela 3, Mike Kama 3, Meciusela Tuicakau 3, Lucia Romani 4, Margot J. Whitfeld 5, Christopher L. King 6, Gary J. Weil 7, Tibor Schuster [...]
- Published
- 2021
- Full Text
- View/download PDF
26. IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis
- Author
-
Greene, Sarah E., primary, Huang, Yuefang, additional, Curtis, Kurt C., additional, King, Christopher L., additional, Fischer, Peter U., additional, and Weil, Gary J., additional
- Published
- 2023
- Full Text
- View/download PDF
27. A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis
- Author
-
Opoku, Nicholas O., primary, Doe, Felix, additional, Dubben, Bettina, additional, Fetcho, Nicole, additional, Fischer, Kerstin, additional, Fischer, Peter U., additional, Gordor, Shelter, additional, Goss, Charles W., additional, Gyasi, Michael E., additional, Hoerauf, Achim, additional, Hong, Augustine R., additional, Kanza, Eric, additional, King, Christopher L., additional, Laryea, Ruth, additional, Lew, Daphne, additional, Seidu, Mahmood A., additional, and Weil, Gary J., additional
- Published
- 2023
- Full Text
- View/download PDF
28. Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers
- Author
-
Nugent, Clare, primary, Abul, Yasin, additional, White, Elizabeth M., additional, Shehadeh, Fadi, additional, Kaczynski, Matthew, additional, Oscar Felix, Lewis, additional, Ganesan, Narchonai, additional, Oyebanji, Oladayo A., additional, Vishnepolskiy, Igor, additional, Didion, Elise M., additional, Paxitzis, Alexandra, additional, Sheehan, Maegan L., additional, Chan, Philip A., additional, Pfeifer, Walther M., additional, Dickerson, Evan, additional, Kamojjala, Shreya, additional, Wilson, Brigid M., additional, Mylonakis, Eleftherios, additional, King, Christopher L., additional, Balazs, Alejandro B., additional, Canaday, David H., additional, and Gravenstein, Stefan, additional
- Published
- 2023
- Full Text
- View/download PDF
29. Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.
- Author
-
Sobhani, Kimia, Cheng, Susan, Binder, Raquel A., Mantis, Nicholas J., Crawford, James M., Okoye, Nkemakonam, Braun, Jonathan G., Joung, Sandy, Wang, Minhao, Lozanski, Gerard, King, Christopher L., Roback, John D., Granger, Douglas A., Boppana, Suresh B., and Karger, Amy B.
- Subjects
MULTISYSTEM inflammatory syndrome in children ,SERODIAGNOSIS ,HUMORAL immunity ,GENETIC vectors ,NEUTRALIZATION tests ,HEPATITIS B - Abstract
Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures. In the transition from the COVID-19 pandemic to endemic, there has been much interest in defining an antibody CoP. Due to the high mutability of respiratory viruses and our current knowledge of SARS-CoV-2 variants defining a CoP for prevention of infection is unrealistic. However, a CoP may be defined for prevention of severe disease requiring hospitalization and/or death. Most SARS-CoV-2 CoP research has focused on neutralization measurements. However, there can be significant differences in neutralization test methods, and disparate responses to new variants depending on format. Furthermore, neutralization assays are often impractical for high throughput applications (e.g., assessing humoral immune response in populations or large cohorts). Nevertheless, CoP studies using neutralization measures are reviewed to determine where there is consensus. Alternatively, binding antibody tests could be used to define a CoP. Binding antibody assays tend to be highly automatable, high throughput, and therefore practical for large population applications. Again, we review studies for consensus on binding antibody responses to vaccines, focusing on standardized results. Binding antibodies directed against the S1 receptor binding domain (S1-RBD) of the viral spike protein can provide a practical, indirect measure of neutralization. Initially, a response for S1-RBD antibodies may be selected that reflects the peak response in immunocompetent populations and may serve as a target for booster dosing in the immunocompromised. From existing studies reporting peak S1-RBD responses in standardized units, an approximate range of 1372–2744 BAU/mL for mRNA and recombinant protein vaccines was extracted that could serve as an initial CoP target. This target would need to be confirmed and potentially adjusted for updated vaccines, and almost certainly for other vaccine formats (i.e., viral vector). Alternatively, a threshold or response could be defined based on outcomes over time (i.e., prevention of severe disease). We also discuss the precedent for clinical measurement of antibodies for vaccine-preventable diseases (e.g., hepatitis B). Lastly, cellular immunity is briefly addressed for its importance in the nature and durability of protection. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
30. Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers
- Author
-
Freeman, Michael L, primary, Oyebanji, Oladayo A, additional, Moisi, Daniela, additional, Payne, Michael, additional, Sheehan, Maegan L, additional, Balazs, Alejandro B, additional, Bosch, Jürgen, additional, King, Christopher L, additional, Gravenstein, Stefan, additional, Lederman, Michael M, additional, and Canaday, David H, additional
- Published
- 2023
- Full Text
- View/download PDF
31. IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis.
- Author
-
Greene, Sarah E., Huang, Yuefang, Curtis, Kurt C., King, Christopher L., Fischer, Peter U., and Weil, Gary J.
- Subjects
RECOMBINANT antibodies ,BURULI ulcer ,FILARIASIS ,NEGLECTED diseases ,ANTIGENS ,BLOOD parasites - Abstract
Background: Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment. Methodology/principal findings: IgG
4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to Wb-Bhp-1 and Wb123, but not Bm14, were significantly higher in participants with persistent microfilaremia 24 months after treatment. Antibodies to all three antigens declined significantly by 60 months after treatment with ivermectin, diethylcarbamazine and albendazole despite circulating filarial antigen in 76% of participants. By 60 months follow up, antibodies to Wb-Bhp-1, Wb123, and Bm14 were detected in 17%, 7% and 90% of participants, respectively. Antibodies to Wb-Bhp-1 also declined more rapidly after treatment than antibodies to Bm14 in samples from a clinical trial conducted in Sri Lanka. We also tested archived serum samples from people living in filariasis-endemic communities in Egypt with different infection profiles. Antibodies to Wb-Bhp-1 were detected in 73% of microfilaremic people, 53% of amicrofilaremic people with circulating filarial antigen, and 17.5% of endemic individuals without microfilaria or circulating filarial antigen. Tests performed with legacy samples from India showed that few people with filarial lymphedema had antibodies to these recombinant antigens. Conclusions: Antibodies to Wb-Bhp-1 and Wb123 are more closely correlated with persistent microfilaremia than circulating filarial antigenemia or antibodies to Bm14, and they clear more rapidly after anti-filarial treatment. Additional studies are needed to assess the value of Wb-Bhp-1 serology as a tool for determining the success of LF elimination efforts. Author summary: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination by the World Health Organization. Public health programs aim to eliminate the infection with repeated rounds of mass distribution of anti-filarial medicines in areas with LF. These mass drug administration campaigns have been highly successful. Improved diagnostic tests are needed to monitor and verify the success of infection elimination efforts. We have previously shown that detection of antibodies to the recombinant parasite protein Wb-Bhp-1 are sensitive and specific for diagnosis of active filarial infections. Here, we show that antibodies to Wb-Bhp-1 are correlated with the persistence of filarial parasites in the blood after treatment, and that they decrease after effective anti-filarial treatment. Importantly, antibodies to Wb-Bhp-1 decrease after treatment more rapidly than other diagnostic markers such as circulating filarial antigenemia or antibodies to Bm14. Thus, this antibody test may be useful as a tool for monitoring the success of filariasis elimination programs. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
32. Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis.
- Author
-
Alshehri, Abdullah, Chhonker, Yashpal S., Bala, Veenu, Edi, Constant, Bjerum, Catherine M., Koudou, Benjamin G., John, Lucy N., Mitjà, Oriol, Marks, Michael, King, Christopher L., and Murry, Daryl J.
- Subjects
FILARIASIS ,DRUG administration ,PHARMACOKINETICS ,IVERMECTIN ,POISONS - Abstract
Background: Ivermectin (IVM) is a broad–spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple–drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub–Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single–oral dose in LF–infected subjects and healthy individuals. Methodology / Principal findings: In this analysis, 724 samples were collected from treatment–naïve Wuchereria bancrofti–infected (n = 32) and uninfected (n = 24) adults living in Côte d'Ivoire who had received one dose of IVM as a part of triple–drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two–compartment model with zero–order dose input into the absorption compartment with a lag time function followed by first–order absorption and linear elimination best described the IVM's pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex. Conclusion/Significance: We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF. Trial registration: NCT02845713; NCT03664063 Author summary: Ivermectin has been shown to be a valuable tool in mass drug administration campaigns against lymphatic filariasis. The drug shows high variability in drug exposure in previous pharmacokinetic studies. Variability in drug exposure can lead to either a higher exposure with the potential for toxic effects or a lower exposure that may result in treatment failure. Identifying and quantifying the source of high variability using non–linear mixed effects modeling is crucial for future dosing recommendations that seek to maximize therapeutic benefit while minimizing toxicity risks. In this study, the variability of IVM exposure after a single oral dose was investigated with a population pharmacokinetic model using data from Lymphatic filariasis infected subjects and healthy individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
33. A simple, high-throughput and validated LC-MS/MS method for the determination of azithromycin in human plasma and its application to a clinical pharmacokinetic study
- Author
-
Zhang, Yuning, Bala, Veenu, Chhonker, Yashpal S, Aldhafiri, Wafaa N, John, Lucy N, Bjerum, Catherine M, King, Christopher L, Mitja, Oriol, Marks, Michael, and Murry, Daryl J
- Abstract
A sensitive, specific and rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated to quantify azithromycin concentrations in human plasma. Azithromycin (AZI) is the most common outpatient prescribed antibiotic in the US and clinical studies have demonstrated the efficacy and safety of AZI in many bacterial infections. To support a clinical study, we developed a high-throughput LC-MS/MS method to process up to 250 samples per day to quantify AZI in human plasma. Samples were prepared by solid-phase extraction. Separation was achieved with an ACE C18 column (2.1 × 100 mm, 1.7 μm) equipped with a C18 guard column. The mobile phase consisted of 0.1% formic acid and methanol-acetonitrile (1:1, v/v) at a flow rate of 0.25 ml/min. The ionization was optimized with positive electrospray source using multiple reaction monitoring transition, m/z 749.50 > 591.45 for AZI and m/z 754.50 > 596.45 for AZI-d5. Extraction recoveries were approximately 90% for AZI. The assay was linear from 0.5 to 2,000 ng/ml and required only 100 μl of plasma with a total analysis time of 4.5 min. The method was successfully applied to pharmacokinetic studies of a weight-based dosing protocol for AZI.
- Published
- 2022
34. COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents
- Author
-
Canaday, David H., primary, Oyebanji, Oladayo A., additional, White, Elizabeth, additional, Keresztesy, Debbie, additional, Payne, Michael, additional, Wilk, Dennis, additional, Carias, Lenore, additional, Aung, Htin, additional, St. Denis, Kerri, additional, Sheehan, Maegan L., additional, Berry, Sarah D., additional, Cameron, Cheryl M., additional, Cameron, Mark J., additional, Wilson, Brigid M., additional, Balazs, Alejandro B., additional, King, Christopher L., additional, and Gravenstein, Stefan, additional
- Published
- 2022
- Full Text
- View/download PDF
35. Characterization of a novel microfilarial antigen for diagnosis of Wuchereria bancrofti infections
- Author
-
Greene, Sarah E., primary, Fischer, Kerstin, additional, Choi, Young-Jun, additional, Curtis, Kurt C., additional, Budge, Philip J., additional, Mitreva, Makedonka, additional, King, Christopher L., additional, Fischer, Peter U., additional, and Weil, Gary J., additional
- Published
- 2022
- Full Text
- View/download PDF
36. Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected with Schistosoma and Plasmodium Parasites
- Author
-
Nyakundi, Ruth K., Hau, Jann, Ogongo, Paul, Nyamongo, Onkoba, Jeneby, Maamum, Akinyi, Mercy, Mulei, Isaac, Nyundo, Fred, Farah, Idle, Malhotra, Indu, Ozwara, Hastings, King, Christopher L., Kariuki, Thomas, Nyakundi, Ruth K., Hau, Jann, Ogongo, Paul, Nyamongo, Onkoba, Jeneby, Maamum, Akinyi, Mercy, Mulei, Isaac, Nyundo, Fred, Farah, Idle, Malhotra, Indu, Ozwara, Hastings, King, Christopher L., and Kariuki, Thomas
- Abstract
Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons (n = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections. One of the two groups was treated with praziquantel (PZQ) to eliminate schistosome infection. The two groups plus a new malaria control group (n = 8) were inoculated three times with Plasmodium knowlesi parasites at 1-month intervals. Clinical data and IgG, IgG1, memory T-cell, and monocyte levels were recorded. After three P. knowlesi infections, we observed (i) reduced clinical symptoms in all groups with each subsequent infection, (ii) increased IgG and IgG1 levels in the malaria control (Pk-only) group, (iii) increased IgG, IgG1, CD141, and CD142 CD161 levels in the Schistosoma-treated (Schisto/PZQ1Pk) group, and (iv) significantly lower IgG and IgG1 levels compared to those of the Pk-only group, reduced CD41 CD45RO1 levels, and increased levels of CD142 CD161 cells in the coinfected (Schisto1Pk) group. Chronic S. mansoni infection does not compromise establishment of clinical immunity after multiple malaria infections, with nonclassical monocytes seeming to play a role. Failure to develop robust antibody and memory T cells may have a long-term impact on acquired immunity to malaria infection.
- Published
- 2022
37. Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d’Ivoire
- Author
-
Ouattara, Allassane F, primary, Bjerum, Catherine M, additional, Aboulaye, Méité, additional, Kouadio, Olivier, additional, Marius, Vanga K, additional, Andersen, Britt, additional, Lew, Daphne, additional, Goss, Charles W, additional, Weil, Gary J, additional, Koudou, Benjamin G, additional, and King, Christopher L, additional
- Published
- 2022
- Full Text
- View/download PDF
38. The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization
- Author
-
Karger, Amy B., primary, Brien, James D., additional, Christen, Jayne M., additional, Dhakal, Santosh, additional, Kemp, Troy J., additional, Klein, Sabra L., additional, Pinto, Ligia A., additional, PREMKUMAR, LAKSHMANANE, additional, Roback, John D., additional, Binder, Raquel A., additional, Boehme, Karl William, additional, Boppana, Suresh, additional, Crawford, James M., additional, Daiss, John L, additional, Dupuis, Alan P., additional, Espino, Ana M, additional, Forconi, Catherine, additional, Forrest, J. Craig, additional, Girardin, Roxie C., additional, Haddad, Natalie S., additional, Heaney, Christopher D, additional, Hunt, Danielle T., additional, Kennedy, Joshua L, additional, King, Christopher L., additional, Kruczynski, Kate, additional, LaBaer, Joshua, additional, Lee, F. Eun-Hyung, additional, Lee, William T., additional, Liu, Shan-Lu, additional, Lozanski, Gerard, additional, Moormann, Ann M., additional, Murugan, Vel, additional, Okoye, Nkemakonam C., additional, Pantoja, Petraleigh, additional, Payne, Anne F., additional, Park, Jin, additional, Pinninti, Swetha, additional, Pinto, Amelia K, additional, Pisanic, Nora, additional, Qiu, Ji, additional, Sariol, Carlos A, additional, Song, Lusheng, additional, Steffen, Tara L., additional, Stone, E. Taylor, additional, Styer, Linda M., additional, Suthar, Mehul S, additional, Thomas, Stefani N., additional, Thyagarajan, Bharat, additional, Yates, Jennifer L, additional, and Sobhani, Kimia, additional
- Published
- 2022
- Full Text
- View/download PDF
39. Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected with Schistosoma and Plasmodium Parasites
- Author
-
Nyakundi, Ruth K., primary, Hau, Jann, additional, Ogongo, Paul, additional, Nyamongo, Onkoba, additional, Jeneby, Maamum, additional, Akinyi, Mercy, additional, Mulei, Isaac, additional, Nyundo, Fred, additional, Farah, Idle, additional, Malhotra, Indu, additional, Ozwara, Hastings, additional, King, Christopher L., additional, and Kariuki, Thomas, additional
- Published
- 2022
- Full Text
- View/download PDF
40. Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial
- Author
-
Tavul, Livingstone, primary, Laman, Moses, additional, Howard, Cade, additional, Kotty, Bethuel, additional, Samuel, Anna, additional, Bjerum, Catherine, additional, O’Brian, Kobie, additional, Kumai, Steven, additional, Amuga, Matthew, additional, Lorry, Lina, additional, Kerry, Zebedee, additional, Kualawi, Melvin, additional, Karl, Stephan, additional, Makita, Leo, additional, John, Lucy N., additional, Bieb, Sibauk, additional, Wangi, James, additional, Weil, Gary J., additional, Goss, Charles W., additional, Tisch, Daniel J., additional, Pomat, William, additional, King, Christopher L., additional, and Robinson, Leanne J., additional
- Published
- 2022
- Full Text
- View/download PDF
41. A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana
- Author
-
Opoku, Nicholas O., primary, Gyasi, Michael E., additional, Doe, Felix, additional, Lew, Daphne, additional, Hong, Augustine R., additional, Chithenga, Sithembele, additional, Fischer, Peter U., additional, King, Christopher L., additional, and Weil, Gary J., additional
- Published
- 2022
- Full Text
- View/download PDF
42. Significantly elevated antibody levels and neutralization titers in nursing home residents after SARS-CoV-2 BNT162b2 mRNA booster vaccination
- Author
-
Canaday, David H., primary, Oyebanji, Oladayo A., additional, White, Elizabeth, additional, Keresztesy, Debbie, additional, Payne, Michael, additional, Wilk, Dennis, additional, Carias, Lenore, additional, Aung, Htin, additional, Denis, Kerri St., additional, Sheehan, Maegan L., additional, Berry, Sarah D., additional, Cameron, Cheryl M., additional, Cameron, Mark J., additional, Wilson, Brigid M., additional, Balazs, Alejandro B., additional, King, Christopher L., additional, and Gravenstein, Stefan, additional
- Published
- 2021
- Full Text
- View/download PDF
43. Significant Reduction in Vaccine-Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination
- Author
-
Canaday, David H, primary, Oyebanji, Oladayo A, additional, Keresztesy, Debbie, additional, Payne, Michael, additional, Wilk, Dennis, additional, Carias, Lenore, additional, Aung, Htin, additional, St. Denis, Kerri, additional, Lam, Evan C, additional, Rowley, Christopher F, additional, Berry, Sarah D, additional, Cameron, Cheryl M, additional, Cameron, Mark J, additional, Wilson, Brigid M, additional, Balazs, Alejandro B, additional, King, Christopher L, additional, and Gravenstein, Stefan, additional
- Published
- 2021
- Full Text
- View/download PDF
44. Significant Reduction in Vaccine-Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination.
- Author
-
Canaday, David H, Oyebanji, Oladayo A, Keresztesy, Debbie, Payne, Michael, Wilk, Dennis, Carias, Lenore, Aung, Htin, Denis, Kerri St., Lam, Evan C, Rowley, Christopher F, Berry, Sarah D, Cameron, Cheryl M, Cameron, Mark J, Wilson, Brigid M, Balazs, Alejandro B, King, Christopher L, and Gravenstein, Stefan
- Subjects
IMMUNOGLOBULINS ,COVID-19 vaccines ,IMMUNOASSAY ,MESSENGER RNA ,NEUTRALIZATION tests ,RESEARCH funding ,POLYMERASE chain reaction - Abstract
Antibody decline occurred from 2 weeks to 6 months post-BNT162b2 mRNA vaccination in nursing home (NH) residents and healthcare workers. Antispike, receptor-binding domain, and neutralization levels dropped >81% irrespective of prior infection. Notably, 69% of infection-naive NH residents had neutralizing antibodies at or below the assay's limit of detection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. Reduced BNT162b2 Messenger RNA Vaccine Response in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)–Naive Nursing Home Residents.
- Author
-
Canaday, David H, Carias, Lenore, Oyebanji, Oladayo A, Keresztesy, Debbie, Wilk, Dennis, Payne, Michael, Aung, Htin, Denis, Kerri St., Lam, Evan C, Rowley, Christopher F, Berry, Sarah D, Cameron, Cheryl M, Cameron, Mark J, Wilson, Brigid, Balazs, Alejandro B, Gravenstein, Stefan, and King, Christopher L
- Subjects
COVID-19 ,COVID-19 vaccines ,TREATMENT effectiveness ,VIRAL antibodies - Abstract
After BNT162b2 messenger RNA vaccination, antibody levels to spike, receptor-binding domain, and virus neutralization were examined in 149 nursing home residents and 110 healthcare worker controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–naive nursing home residents' median post–second vaccine dose antibody neutralization titers are one-quarter that of SARS-CoV-2–naive healthcare workers. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
46. Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.
- Author
-
Winnicki AC, King CL, Bosch J, Malachin AN, Carias LL, Skomorovska-Prokvolit Y, Tham WH, Dietrich MH, Popovici J, Roobsoong W, Beeson JG, Sattabongkot J, Yeoh LM, Opi DH, Feufack-Donfack LB, Orban A, Drago CL, McLaine OS, Redinger KR, Jung NC, Baldor L, Kirtley P, Neilsen K, Aleshnick M, Zanghi G, Rezakhani N, Vaughan AM, and Wilder BK
- Abstract
New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. We isolated 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. HumAb 826827 blocked the invasion of human erythrocytes using Pv clinical isolates and inhibited sporozoite invasion of human hepatocytes in vitro (IC50 of 0.3 to 3.7 ug/mL). It also significantly reduced liver infection of chimeric FRG humHep mice in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate transcendent, blocks both pre erythrocytic and blood stage infection, and could be a new therapy for Pv.
- Published
- 2024
- Full Text
- View/download PDF
47. Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.
- Author
-
Abul Y, Nugent C, Vishnepolskiy I, Wallace T, Dickerson E, Holland L, Esparza I, Winkis M, Wali KT, Chan PA, Baier RR, Recker A, Kaczynski M, Kamojjala S, Pralea A, Rice H, Osias O, Oyebanji OA, Olagunju O, Cao Y, Li CJ, Roederer A, Pfeifer WM, King CL, Bosch J, Nanda A, McNicoll L, Mujahid N, Raza S, Tyagi R, Wilson BM, White EM, Canaday DH, Gravenstein S, and Balazs AB
- Abstract
Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs., Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination., Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection., Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination., Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake., Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.
- Published
- 2024
- Full Text
- View/download PDF
48. The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study.
- Author
-
Habtamu K, Getachew H, Abossie A, Demissew A, Tsegaye A, Degefa T, Wang X, Lee MC, Zhou G, Kibret S, King CL, Kazura JW, Petros B, Yewhalaw D, and Yan G
- Abstract
Background: To interrupt residual malaria transmission and achieve successful elimination of P. falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of hemolysis in patients with G6PD deficiency (G6PDd), PQ use is not as common. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency., Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and hemoglobin (Hb) concentrations. G6PD levels were masured by a quantiative biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone., Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 14) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to -0.47) in patients treated with ACT alone ( P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PD deficiency group (-0.56 g/dL) than in the G6PD normal group (-0.39 g/dL); however, there was no statistically significant difference ( P = 0.359). Overall, D14 losses were 0.10 g/dl (95% CI = -0.00 to 0.20) and 0.05 g/dl (95% CI = -0.123 to 0.22) in patients with and without SLD-PQ, respectively ( P = 0.412)., Conclusions: Our findings showed that single low-dose primaquine (SLD-PQ) treatment for uncomplicated P. falciparum malaria is safe and does not increase the risk of hemolysis in G6PDd patients. This evidence suggests that the wider deployment of SLD-PQ for P. falciparum is part of a global strategy for eliminating P. falciparum malaria.
- Published
- 2024
- Full Text
- View/download PDF
49. Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.
- Author
-
Gravenstein S, DeVone F, Oyebanji OA, Abul Y, Cao Y, Chan PA, Halladay CW, McConeghy KW, Nugent C, Bosch J, King CL, Wilson BM, Balazs AB, White EM, and Canaday DH
- Abstract
Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents., Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine., Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost., Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.
- Published
- 2023
- Full Text
- View/download PDF
50. Naturally-acquired and Vaccine-induced Human Monoclonal Antibodies to Plasmodium vivax Duffy Binding Protein Inhibit Invasion of Plasmodium knowlesi (PvDBPOR) Transgenic Parasites.
- Author
-
Watson QD, Carias LL, Malachin A, Redinger KR, Bosch J, Bardelli M, Moon RW, Draper SJ, Zimmerman PA, and King CL
- Abstract
The Duffy antigen receptor for chemokines (DARC) expressed on erythrocytes is central to Plasmodium vivax (Pv) invasion of reticulocytes. Pv expresses a Duffy binding protein (PvDBP) on merozoites, a DARC ligand, and their protein-protein interaction is central to vivax blood stage malaria. Here we compared the functional activity of humAbs derived from naturally exposed and vaccinated individuals for the first time using easily cultured P. knowlesi (Pk) that had been genetically modified to replace its endogenous PkDBP orthologue with PvDBP to create a transgenic parasite, PkPvDBPOR. This transgenic parasite requires DARC to invade human erythrocytes but is not reticulocyte restricted. Using this model, we evaluated the invasion inhibition potential of 12 humAbs (9 naturally acquired; 3 vaccine-induced) targeting PvDBP individually and in combinations using growth inhibition assays (GIAs). The PvDBP-specific humAbs demonstrated 70-100% inhibition of PkPvDBPOR invasion with the IC
50 values ranging from 51 to 338 μg/mL for the 9 naturally acquired (NA) humAbs and 33 to 99 μg/ml for the 3 vaccine-induced (VI) humAbs. To evaluate antagonistic, additive, or synergistic effects, six pairwise combinations were performed using select humAbs. Of these combinations tested, one NA/NA (099100/094083) combination demonstrated relatively strong additive inhibition between 10-100 μg/mL; all combinations of NA and VI humAbs showed additive inhibition at concentrations below 25 μg/mL and antagonism at higher concentrations. None of the humAb combinations showed synergy. This PkPvDBPOR model system enables efficient assessment of NA and VI humAbs individually and in combination.- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.