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2.
J Exp Med ; 218(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34342640

RESUMO

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.


Assuntos
Antígenos de Protozoários/metabolismo , Membrana Eritrocítica/parasitologia , Malária Falciparum/parasitologia , Merozoítos/metabolismo , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/genética , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Pré-Escolar , Feminino , Interações Hospedeiro-Parasita/fisiologia , Humanos , Lactente , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Malária Falciparum/mortalidade , Merozoítos/imunologia , Camundongos Endogâmicos BALB C , Plasmodium falciparum/imunologia , Plasmodium falciparum/patogenicidade , Polimorfismo de Nucleotídeo Único , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Tanzânia
6.
J Infect Dis ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009376

RESUMO

BACKGROUND: We hypothesized that nationwide social distancing and other preventive measures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with reduced detection of other respiratory viruses in South Korea. METHODS: We analyzed national surveillance data to compare incidence of respiratory viruses during 2016-2019 vs. 2020. Results of multiplex reverse transcriptase-polymerase chain reaction assays for eight respiratory viruses were included: adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), influenza virus (IFV), human coronavirus (HCoV; non-SARS-CoV-2), human rhinovirus (HRV), human bocavirus (HBoV), and human metapneumovirus (HMPV). RESULTS: During 2016-2019, rates of detection of respiratory viruses were relatively stable: ADV, 3.7%-9.2%; PIV, 1.4%-17.0%; RSV, 0.3%-15.3%; IFV, 0.4%-35.6%; HCoV, 1.5%-8.4%; HRV, 7.0%-25.1%; HBoV, 0.6%-6.3%; and HMPV, 0.7%-14.5%. Following implementation of social distancing in February 2020, rates of detection of enveloped viruses (HCoV, HMPV, IFV, PIV and RSV) were significantly reduced by up to 100%. However, non-enveloped viruses (ADV, HRV and HBoV) persisted throughout 2020, and HRV rates in hospitalized patients significantly increased. CONCLUSIONS: After implementation of social distancing for SARS-CoV-2 in South Korea, rates of detection of enveloped respiratory viruses decreased significantly, whereas non-enveloped viruses persisted, suggesting that enhanced infection prevention strategies are required to mitigate spread of these viruses.

7.
Pediatr Res ; 89(5): 1078-1086, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32971527

RESUMO

Zero to 19 year-old children in sub-Saharan Africa bear a disproportionate proportion of the global burden of communicable and non-communicable diseases. Significant public health gains have been made in the fight against these diseases, however, factors such as underequipped health systems, disease outbreaks, conflict, and political instability continue to challenge prevention and control. The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduces new challenges to public health programs in sub-Saharan Africa. Of particular concern are programs targeting major conditions among children, such as undernutrition, vaccine-preventable pneumonia and diarrhea, malaria, tuberculosis, HIV, and sickle cell disease. This article focuses on the impact of the COVID-19 pandemic on child health in sub-Saharan Africa. We review the epidemiology of major pediatric diseases and, referencing modeling projections, discuss the short- and long-term impact of the pandemic on major disease control. We deliberate on potential complications of SARS-CoV-2 co-infections/co-morbidities and identify critical social and ethical issues. Furthermore, we highlight the paucity of COVID-19 data and clinical trials in this region and the lack of child participants in ongoing studies. Lastly, approaches and interventions to mitigate the pandemic's impact on child health outcomes are discussed. IMPACT: Children in sub-Saharan Africa bear a disproportionate burden of communicable and non-communicable diseases globally; this remains true even as the COVID-19 pandemic persists. Amidst the fast-expanding COVID-19 literature, there is little comprehensive coverage of the pandemic's indirect impact on child health in sub-Saharan Africa. This article comprehensively outlines the threat that the pandemic poses to major disease prevention and control for children in sub-Saharan Africa. It discusses the potential impact of SARS-CoV-2 co-infections/co-morbidities, highlights research gaps, and advocates for data and action to mitigate the ripple effects of the pandemic on this population.


Assuntos
COVID-19/epidemiologia , Serviços de Saúde da Criança/tendências , Saúde da Criança , Atenção à Saúde , Pandemias , Serviços Preventivos de Saúde/tendências , SARS-CoV-2 , Adolescente , África ao Sul do Saara/epidemiologia , Anemia Falciforme/epidemiologia , Criança , Maus-Tratos Infantis/prevenção & controle , Serviços de Saúde da Criança/organização & administração , Pré-Escolar , Ensaios Clínicos como Assunto , Comorbidade , Efeitos Psicossociais da Doença , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Malária/epidemiologia , Malária/prevenção & controle , Masculino , Desnutrição/epidemiologia , Seleção de Pacientes , Serviços Preventivos de Saúde/organização & administração , Tuberculose/epidemiologia , Doenças Preveníveis por Vacina/epidemiologia , Ferimentos e Lesões/epidemiologia , Adulto Jovem
8.
Rev Med Virol ; 31(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845042

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.


Assuntos
COVID-19 , Índice de Gravidade de Doença , Adulto , Envelhecimento , Biomarcadores , COVID-19/mortalidade , COVID-19/patologia , COVID-19/transmissão , Criança , Comorbidade , Humanos , Hipóxia/patologia , Prognóstico , SARS-CoV-2/patogenicidade
9.
Open Forum Infect Dis ; 7(11): ofaa443, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204751

RESUMO

In the context of the coronavirus disease 2019 pandemic, we aimed to systematically address the global seasonal patterns of human coronavirus (HCoV) infections. We identified relevant articles from MEDLINE, EMBASE, and CINAHL Plus as of May 11, 2020. The main outcomes were the peak months of HCoV infections each year and the months during which more than 5% of positive respiratory specimen tests were attributable to HCoV. Of 707 articles reviewed, 22 met the inclusion criteria. The annual percentage of HCoV infections reached a peak in February globally. We found a higher HCoV positivity rate among studies that tested only children (median: 5.9%, range: 0.9%-18.4%), compared with other studies of adults alone (median: 5.2%, range: 3.3%-7.1%) or the entire population (median: 1.9%, range: 0.2%-8.1%). We found the largest global peak of HCoV during the winter season, with the highest rate of positivity among children.

10.
Clin Microbiol Infect ; 26(12): 1690.e5-1690.e8, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919073

RESUMO

OBJECTIVES: The aim of this study was to assess the co-seasonality and co-detection of respiratory viral infections and bacteraemia in children since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Children <18 years old were eligible for inclusion if they had a respiratory infection and a positive PCR-based assay for respiratory viruses as well as a positive blood culture between 2010 and 2018 at a single referral centre in the United States, regardless of their underlying medical condition or antibiotic treatment history. Monthly incidence rates of respiratory viruses and bacteraemia were analysed with a seasonal-trend decomposition procedure based on loess (STL) and cross-correlation functions using time series regression modelling. RESULTS: We identified 7415 unique positive respiratory virus tests, including 2278 respiratory syncytial virus (RSV) (31%), 1825 influenza viruses (24%), 1036 parainfluenza viruses (14%), 1017 human metapneumovirus (hMPV) (14%), 677 seasonal coronaviruses (9%), and 582 adenoviruses (8%), together with a total of 11 827 episodes of bacteraemia. Significant co-seasonality was found between all-cause bacteraemia and RSV (OR = 1.76, 95%CI 1.50-2.06, p < 0.001), influenza viruses (OR = 1.38, 95%CI 1.13-1.68, p 0.002), and seasonal coronaviruses (OR = 1.18, 95%CI 1.09-1.28, p < 0.001), respectively. Analysis of linked viral-bacterial infections in individual children indicated that the rate ratio (RR) of bacteraemia associated with hMPV (RR = 2.73, 95%CI 1.12-6.85, p 0.019) and influenza (RR = 2.61, 95%CI 1.21-6.11, p 0.013) were more than double that of RSV. Staphylococcus aureus and Streptococcus pneumoniae were the most commonly identified pathogens causing bacteraemia. CONCLUSIONS: There is a significant association between hMPV and influenza viruses and bacteraemia of all causes in hospitalized children at a single paediatric centre in the United States. Large multicentre studies are needed to confirm these findings and to elucidate the mechanisms by which hMPV potentiates the virulence and invasive capacity of diverse bacteria.


Assuntos
Bacteriemia , Vacinas Pneumocócicas , Infecções Respiratórias , Adolescente , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Estações do Ano , Vacinação/estatística & dados numéricos , Vírus/isolamento & purificação
11.
Pediatr Res ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942286

RESUMO

BACKGROUND: There are sparse patient-level data available for children with novel coronavirus disease (COVID-19). Therefore, there is an urgent need for an updated systematic literature review that analyzes individual children rather than aggregated data in broad age groups. METHODS: Six databases (MEDLINE, Scopus, Web of Science, CINAHL, Google Scholar, medRxiv) were searched for studies indexed from January 1 to May 15, 2020, with MeSH terms: children, pediatrics, COVID-19, SARS-CoV-2. 1241 records were identified, of which only unique papers in English with individual patient information and documented COVID-19 testing were included. This review of 22 eligible studies followed Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. RESULTS: A total of 123 patients from five countries were identified. 46% were females. The median age was 5 years (IQR = 8). At presentation, 62% had a fever, 32% had a cough, 58% had a single symptom, and 21% were asymptomatic. Abnormal chest imaging was seen in 62% (65/105) of imaged and 76.9% (20/26) of asymptomatic children. A minority of children had elevated platelets, CRP, lactate dehydrogenase, and D-dimer. CONCLUSION: Data from this independent participant data systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. IMPACT: This systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. By using an independent participant data approach, this analysis underscores the challenge of diagnosing COVID-19 in pediatric patients due to the wide variety of symptoms and seemingly poor correlation of imaging findings with symptomatic disease. The data presented from individual patients from case series or cohort studies add more granularity to the current description of pediatric COVID-19.

12.
Pediatr Rheumatol Online J ; 18(1): 31, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293478

RESUMO

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. METHODS: The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. RESULTS: The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. CONCLUSION: The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.


Assuntos
Febre/terapia , Linfadenite/terapia , Faringite/terapia , Estomatite Aftosa/terapia , Corticosteroides/uso terapêutico , Comitês Consultivos , Antipiréticos/uso terapêutico , Criança , Pré-Escolar , Cimetidina/uso terapêutico , Colchicina/uso terapêutico , Febre/fisiopatologia , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Linfadenite/fisiopatologia , Pescoço , Faringite/fisiopatologia , Estomatite Aftosa/fisiopatologia , Síndrome , Tonsilectomia , Moduladores de Tubulina/uso terapêutico
13.
Clin Infect Dis ; 71(9): e454-e464, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-32129457

RESUMO

BACKGROUND: Clinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO). METHODS: Consecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses. RESULTS: The causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2-6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3-7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5-14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4-19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2-4 days after antibiotics (OR, 2.7 [95% CI, 1.0-7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1-10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1-21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%. CONCLUSIONS: Two novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO.


Assuntos
Artrite Infecciosa , Osteomielite , Abscesso , Doença Aguda , Criança , Humanos , Osteomielite/epidemiologia , Estudos Retrospectivos
14.
J Infect Dis ; 222(4): 538-550, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32219317

RESUMO

BACKGROUND: Our objective was to quantify the risk of acquiring malaria among progeny of women with malaria during pregnancy. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for eligible prospective studies. The primary predictor was malaria during pregnancy defined as placental malaria, parasitemia, clinical malaria, or pregnancy-associated malaria. Primary outcomes were parasitemia or clinically defined malaria of young children. We performed meta-analyses to pool adjusted risk estimates using a random-effects model. RESULTS: Nineteen of 2053 eligible studies met inclusion criteria for the systemic review. Eleven of these studies were quantitative and were included in the meta-analyses. The pooled adjusted odds ratio (aOR) or adjusted hazard ratio (aHR) of malaria during pregnancy for detection of parasitemia in young children were 1.94 (95% confidence interval [CI], 0.93-4.07; P = .08) and 1.46 (95% CI, 1.07-2.00; P < .001), respectively. The pooled aOR or aHR for clinically defined malaria in young children were 2.82 (95% CI, 1.82-4.38; P < .001) and 1.31 (95% CI, 0.96-1.79; P = .09), respectively. CONCLUSIONS: Our results confirmed that malaria during pregnancy significantly increased the overall risk of malaria in young children via indeterminate mechanisms and emphasize the urgent need to implement safe and highly effective strategies to prevent malaria during pregnancy.


Assuntos
Número de Gestações , Transmissão Vertical de Doenças Infecciosas , Malária/transmissão , Feminino , Humanos , Lactente , Parasitemia , Placenta/parasitologia , Gravidez , Fatores de Risco
15.
J Pediatric Infect Dis Soc ; 9(1): 100-105, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31183496

RESUMO

Cryptococcus albidus, synonymous with Naganishia albida, rarely causes opportunistic infection in immunocompromised individuals. Its clinical features, particularly in children, are not well defined. Here, we report a case of C albidus fungemia in an immunosuppressed child; we also present results of a systematic review, for which we searched PubMed, Embase, and Web of Science using the keywords "cryptococcus" and "albidus." Our goal was to describe the spectrum of disease, diagnostic approaches, therapies, and outcomes. We identified 20 cases of invasive infection, only 2 of which involved children, and 7 cases of noninvasive infection. The reports originated in the Americas, Europe, and Asia. Of those with invasive infection, 16 (80%) patients had an underlying chronic disorder or had received immunosuppressive therapy, 8 (40%) had fungemia, and 6 (30%) had a central nervous system infection. The attributable case fatality rate was 40%. C albidus is an opportunistic yeast that can rarely cause life-threatening fungemia and central nervous system infection in individuals of any age, especially those who are immunocompromised.


Assuntos
Antifúngicos/uso terapêutico , Criptococose , Cryptococcus , Fluconazol/uso terapêutico , Hospedeiro Imunocomprometido , Arterite de Takayasu/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/uso terapêutico , Pré-Escolar , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/etiologia , Criptococose/imunologia , Feminino , Humanos , Recém-Nascido , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/tratamento farmacológico , Transplante Autólogo
16.
Front Immunol ; 10: 77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30891027

RESUMO

Phosphoinositide 3-kinase (PI3K) plays an integral role in lymphocyte function. Mutations in PIK3CD and PIK3R1, encoding the PI3K p110δ and p85α subunits, respectively, cause increased PI3K activity and result in immunodeficiency with immune dysregulation. We describe here the first cases of disseminated and congenital toxoplasmosis in a mother and child who share a pathogenic mutation in PIK3R1 and review the mechanisms underlying susceptibility to severe Toxoplasma gondii infection in activated PI3Kδ syndrome (APDS) and in other forms of primary immunodeficiency.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Síndromes de Imunodeficiência/imunologia , Mutação/genética , Toxoplasma/fisiologia , Toxoplasmose Congênita/imunologia , Adulto , Anticorpos Antiprotozoários/sangue , Criança , Feminino , Humanos , Imunidade Materno-Adquirida , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Lactente , Linfadenopatia , Mães , Fenótipo , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/genética
17.
Clin Infect Dis ; 68(10): 1718-1724, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30165569

RESUMO

BACKGROUND: In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive. METHODS: We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns' resistance to malaria. RESULTS: Children with high cord-blood anti-PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti-PfSEA-1 levels over 12 months of follow-up (P = .03). In 3 trials, pups born to PbSEA-1-vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams. CONCLUSIONS: We demonstrate that maternally-derived, cord-blood anti-PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Sangue Fetal/imunologia , Imunidade Materno-Adquirida , Malária Falciparum/prevenção & controle , Proteínas de Protozoários/imunologia , Índice de Gravidade de Doença , Animais , Antígenos de Protozoários/administração & dosagem , Estudos de Coortes , Resistência à Doença , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária Falciparum/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/imunologia , Parasitemia/prevenção & controle , Plasmodium berghei/imunologia , Plasmodium falciparum , Proteínas de Protozoários/administração & dosagem , Tanzânia , Vacinação
18.
19.
J Infect Dis ; 218(11): 1792-1801, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29982707

RESUMO

Background: Antigametocyte-specific immune responses may regulate Plasmodium falciparum gametocyte density, providing the rationale for pursuing transmission-blocking vaccines (TBVs) that target gametocytes in the human host. Methods: To identify novel antigametocyte TBV antigens, we interrogated the gametocyte proteome with our whole proteome differential screening method using plasma from a treatment-reinfection study conducted in western Kenya. At the start of the high-transmission season, 144 males (12-35 years) were enrolled and treated with quinine and doxycycline, peripheral venous blood samples were obtained, volunteers were observed, and weekly blood films were obtained for 18 weeks to quantify gametocytemia. Using plasma pooled from individuals with low versus high gametocyte carriage, we differentially screened a P falciparum gametocyte stage complementary deoxyribonucleic acid expression library. Results: We identified 8 parasite genes uniquely recognized by gametocyte-resistant but not by gametocyte-susceptible individuals. Antibodies to one of these antigens, PfsEGXP, predicted lower gametocytemia measured over the 18-week transmission season (P = .021). When analyzed dichotomously, anti-PfsEGXP responders had 31% lower gametocyte density over 18 weeks of follow-up, compared with nonresponders (P = .04). Conclusions: PfsEGXP is one of the first reported gametocyte-specific target of antibodies that predict decreased gametocyte density in humans and supports our novel TBV antigen discovery platform.


Assuntos
Anticorpos Antiprotozoários/imunologia , Suscetibilidade a Doenças/imunologia , Malária Falciparum , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/metabolismo , Criança , Humanos , Estágios do Ciclo de Vida/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/genética , Adulto Jovem
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