Browsing by Subject "Infectious disease"

Now showing 1 - 10 of 12
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    Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria
    (Rockefeller University Press, 2019-04-12) Hart, Geoffrey T.; Tran, Tuan M.; Theorell, Jakob; Schlums, Heinrich; Arora, Gunjan; Rajagopalan, Sumati; Sangala, A. D. Jules; Welsh, Kerry J.; Traore, Boubacar; Pierce, Susan K.; Crompton, Peter D.; Bryceson, Yenan T.; Long, Eric O.; Medicine, School of Medicine
    How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss of transcription factor PLZF and Fc receptor γ-chain. Adaptive NK cells dominated antibody-dependent cellular cytotoxicity responses, and their frequency within total NK cells correlated with lower parasitemia and resistance to malaria. P. falciparum–infected RBCs induced NK cell degranulation after addition of plasma from malaria-resistant individuals. Malaria-susceptible subjects with the largest increase in PLZF-negative NK cells during the transmission season had improved odds of resistance during the subsequent season. Thus, antibody-dependent lysis of P. falciparum–infected RBCs by NK cells may be a mechanism of acquired immunity to malaria. Consideration of antibody-dependent NK cell responses to P. falciparum antigens is therefore warranted in the design of malaria vaccines.
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    Advancing Public Health Surveillance in Child Care Centers: Stakeholder-Informed Redesign and User Satisfaction Evaluation of the MCRISP Network
    (JMIR, 2024-09-24) Gribbin, William; Dejonge, Peter; Rodseth, Jakob; Hashikawa, Andrew; Medicine, School of Medicine
    Leveraging user feedback, we redesigned a novel disease monitoring utility to allow for bidirectional data flow and in this letter offer insights into that process as well as lessons learned.
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    Clarifying the HOPE Act landscape: The challenge of donors with false-positive HIV results
    (Wiley, 2020-02) Durand, Christine M.; Werbel, William; Doby, Brianna; Brown, Diane; Desai, Niraj M.; Malinis, Maricar; Price, Jennifer; Chin-Hong, Peter; Mehta, Shikha; Friedman-Moraco, Rachel; Turgeon, Nicole A.; Gilbert, Alexander; Morris, Michele I.; Stosor, Valentina; Elias, Nahel; Aslam, Saima; Santos, Carlos A.Q.; Hand, Jonathan M.; Husson, Jennifer; Pruett, Timothy L.; Agarwal, Avinash; Adebiyi, Oluwafisayo; Pereira, Marcus; Small, Catherine B.; Apewokin, Senu; Lee, Dong Heun; Haidar, Ghady; Blumberg, Emily; Mehta, Sapna A.; Huprikar, Shirish; Florman, Sander S.; Redd, Andrew D.; Tobian, Aaron A.R.; Segev, Dorry L.; Medicine, School of Medicine
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    Commentary: Two to tango and a team to DUET
    (Elsevier, 2021) Blitzer, David; Copeland, Hannah; Indiana University School of Medicine–Fort Wayne
    A multidisciplinary approach to the management of infectious endocarditis resulting from intravenous drug use is an important step toward achieving the best results for these complex patients.
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    Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
    (eLife Sciences, 2023-03-02) Ke, Fang; Benet, Zachary L.; Maz, Mitra P.; Liu, Jianhua; Dent, Alexander L.; Kahlenberg, Joanne Michelle; Grigorova, Irina L.; Microbiology and Immunology, School of Medicine
    Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.
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    Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine
    (American Society for Clinical Investigation, 2024-04-30) Senkpeil, Leetah; Bhardwaj, Jyoti; Little, Morgan R.; Holla, Prasida; Upadhye, Aditi; Fusco, Elizabeth M.; Swanson, Phillip A., II; Wiegand, Ryan E.; Macklin, Michael D.; Bi, Kevin; Flynn, Barbara J.; Yamamoto, Ayako; Gaskin, Erik L.; Sather, D. Noah; Oblak, Adrian L.; Simpson, Edward; Gao, Hongyu; Haining, W. Nicholas; Yates, Kathleen B.; Liu, Xiaowen; Murshedkar, Tooba; Richie, Thomas L.; Sim, B. Kim Lee; Otieno, Kephas; Kariuki, Simon; Xuei, Xiaoling; Liu, Yunlong; Polidoro, Rafael B.; Hoffman, Stephen L.; Oneko, Martina; Steinhardt, Laura C.; Schmidt, Nathan W.; Seder, Robert A.; Tran, Tuan M.; Medicine, School of Medicine
    A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.
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    Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection
    (American Society for Clinical Investigation, 2020-05-19) Obeng-Adjei, Nyamekye; Larremore, Daniel B.; Turner, Louise; Ongoiba, Aissata; Li, Shanping; Doumbo, Safiatou; Yazew, Takele B.; Kayentao, Kassoum; Miller, Louis H.; Traore, Boubacar; Pierce, Susan K.; Buckee, Caroline O.; Lavstsen, Thomas; Crompton, Peter D.; Tran, Tuan M.; Medicine, School of Medicine
    BACKGROUND Malaria pathogenicity is determined, in part, by the adherence of Plasmodium falciparum–infected erythrocytes to the microvasculature mediated via specific interactions between P. falciparum erythrocyte membrane protein (PfEMP1) variant domains and host endothelial receptors. Naturally acquired antibodies against specific PfEMP1 variants can play an important role in clinical protection against malaria. METHODS We evaluated IgG responses against a repertoire of PfEMP1 CIDR domain variants to determine the rate and order of variant-specific antibody acquisition and their association with protection against febrile malaria in a prospective cohort study conducted in an area of intense, seasonal malaria transmission. RESULTS Using longitudinal data, we found that IgG antibodies against the pathogenic domain variants CIDRα1.7 and CIDRα1.8 were acquired the earliest. Furthermore, IgG antibodies against CIDRγ3 were associated with reduced prospective risk of febrile malaria and recurrent malaria episodes. CONCLUSION This study provides evidence that acquisition of IgG antibodies against PfEMP1 variants is ordered and demonstrates that antibodies against CIDRα1 domains are acquired the earliest in children residing in an area of intense, seasonal malaria transmission. Future studies will need to validate these findings in other transmission settings and determine the functional activity of these naturally acquired CIDR variant–specific antibodies. TRIAL REGISTRATION ClinicalTrials.gov NCT01322581.
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    Perceptions of the ethical permissibility of strict travel restrictions to mitigate transmission of SARS-CoV-2
    (Elsevier, 2022) Hartsock, Jane A.; Head, Katharine J.; Kasting, Monica L.; Sturm, Lynne; Zimet, Gregory; Communication Studies, School of Liberal Arts
    Although there has been extensive exploration of public opinion surrounding many non-pharmaceutical interventions (NPIs) aimed at mitigating transmission of SARS-CoV-2 (e.g. mask-wearing and social distancing), there has been less discussion of the public's perception of the ethical appropriateness other NPIs. This paper presents the results of a survey of U.S. adults' opinions of the ethical permissibility of both state-to-state and international travel restrictions to mitigate transmission of SARS-CoV-2. Our research revealed overall high agreement with the ethical permissibility of both state-to-state and international travel restrictions, though we saw significant difference across political party affiliation and conservative/liberal ideologies. Other factors associated with agreement with state-to-state travel restrictions included increasing education, increasing income, and both high and low commitment altruism. When considering international travel restrictions, income, education, and low commitment altruism were associated with increased agreement with the ethical permissibility of international travel restrictions. Ethical analysis and implications are explored.
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    Predicting neurodevelopmental risk in children born to mothers living with HIV in Kenya: protocol for a prospective cohort study (Tabiri Study)
    (BMJ, 2022-04-04) Oyungu, Eren; El Kebbi, Ola; Vreeman, Rachel; Nyandiko, Winstone; Monahan, Patrick O.; Tu, Wanzhu; Khaitan, Alka; Desta, Zeruesenay; Slogrove, Amy L.; Humphrey, John M.; Were, Edwin; Patel, Rena C.; Carlucci, James G.; Wools-Kaloustian, Kara; McHenry, Megan S.; Pediatrics, School of Medicine
    Introduction: For the growing number of children with in utero and postpartum exposure to HIV and/or antiretrovirals, it is unclear which exposures or risk factors play a significant role in predicting worse neurodevelopmental outcomes. This protocol describes a prospective longitudinal cohort study of infants born to mothers living with HIV and those born to mothers without HIV. We will determine which risk factors are most predictive of child neurodevelopment at 24 months. We aim to create a risk assessment tool to help predict which children are at risk for worse neurodevelopment outcomes. Methods and analysis: This study leverages an existing Kenyan cohort to prospectively enrol 500 children born to mothers living with HIV and 500 to those without HIV (n=1000 total) and follow them from birth to age 24 months. The following factors will be measured every 6 months: infectious morbidity and biological/sociodemographic/psychosocial risk factors. We will compare these factors between the two groups. We will then measure and compare neurodevelopment within children in both groups at 24 months of age using the Child Behaviour Checklist and the Bayley Scales of Infant and Toddler Development, third edition. Finally, we will use generalised linear mixed modelling to quantify associations with neurodevelopment and create a risk assessment tool for children ≤24 months. Ethics and dissemination: The study is approved by the Moi University's Institutional Research and Ethics Committee (IREC/2021/55; Approval #0003892), Kenya's National Commission for Science, Technology and Innovation (NACOSTI, Reference #700244) and Indiana University's Institutional Review Board (IRB Protocol #110990). This study carries minimal risk to the children and their mothers, and all mothers will provide written consent for participation in the study. Results will be disseminated to maternal child health clinics within Uasin Gishu County, Kenya and via papers submitted to peer-reviewed journals and presentation at international conferences.
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    Ribonuclease 7 polymorphism rs1263872 reduces antimicrobial activity and associates with pediatric urinary tract infections
    (The American Society for Clinical Investigation, 2021) Pierce, Keith R.; Eichler, Tad; Mosquera Vasquez, Claudia; Schwaderer, Andrew L.; Simoni, Aaron; Creacy, Steven; Hains, David S.; Spencer, John D.; Pediatrics, School of Medicine
    Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7’s antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7’s antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7’s antibacterial activity.