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Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites2, we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant-but not those who are susceptible-to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.
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Apoptosis/inmunología , Péptidos y Proteínas de Señalización Intercelular/inmunología , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Parásitos/inmunología , Plasmodium falciparum/citología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/química , Antígenos de Protozoos/inmunología , Aotidae/inmunología , Aotidae/parasitología , Caspasas/metabolismo , Niño , Estudios de Cohortes , ADN Protozoario/química , ADN Protozoario/metabolismo , Activación Enzimática , Eritrocitos/parasitología , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/química , Kenia , Vacunas contra la Malaria/inmunología , Malaria Falciparum/parasitología , Masculino , Ratones , Parásitos/citología , Parásitos/crecimiento & desarrollo , Plasmodium falciparum/crecimiento & desarrollo , Proteínas Protozoarias/química , Tanzanía , Trofozoítos/citología , Trofozoítos/crecimiento & desarrollo , Trofozoítos/inmunología , Vacuolas/inmunologíaRESUMEN
BACKGROUND: This study aimed to investigate existing evidence regarding the associations of obesity and diabetes with Plasmodium infection and severe malaria in adults. METHODS: We comprehensively searched relevant studies using EMBASE, MEDLINE, Global Health, and CINAHL. The primary exposures were obesity and diabetes. The primary outcomes were Plasmodium infection and severe malaria. We performed meta-analyses to pool unadjusted and adjusted odds ratios (ORs) using a random-effects model. RESULTS: We found 9 studies that met our inclusion criteria; all these studies were eligible for meta-analyses. None of the 9 studies investigated the potential link between obesity and Plasmodium infection. The meta-analysis results showed that there was no statistically significant relationship between obesity and severe malaria (two studies), diabetes and Plasmodium infection (five studies), or diabetes and severe malaria (three studies). CONCLUSION: Our study findings showed that obesity was not associated with severe malaria, and diabetes was not associated with neither Plasmodium infection nor severe malaria. Additional epidemiological studies should be conducted to elucidate the relationships between obesity, diabetes, and Plasmodium infection.
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BACKGROUND: The aim of this study was to compare the predictive performance of three statistical models-logistic regression, classification tree, and structural equation model (SEM)-in predicting severe dengue illness. METHODS/FINDINGS: We adopted modified classification of dengue illness severity based on WHO 1997 guideline. Predictive models were constructed using demographic factors and laboratory indicators on the day of fever occurrence. We developed statistical predictive models using data from two hospital cohorts in Thailand, consisting of 257 Thai children. Different predictive models for each category of severe dengue illness were developed employing logistic regression, classification tree, and SEM. The probability of discrimination of each model for severe output of disease was analyzed with external validation data sets from 55 and 700 patients not used in model development. From external validation using predictors on the day of presentation to the hospital, the area under the receiver operating characteristic curve was between 0.65 and 0.84 for the regression model. It was between 0.73 and 0.85 for SEM models. Classification tree models showed good results of sensitivity, ranging from 0.95 to 0.99. However, they showed poor specificity ranging from 0.10 to 0.44. CONCLUSIONS: Our study showed that SEM is comparable to logistic regression or classification tree, which was widely used for more severe form of dengue prediction.
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BACKGROUND: The objective of this study was to determine the association between water and plasma fluoride and blood pressure (BP) among children and adolescents. METHODS: Our study population was individuals of 8-18 years in the 2013-2016 National Health and Nutrition Examination Survey. We performed a multivariable linear and logistic regression analysis to examine the relationship between fluoride and BP. RESULTS: In a linear regression analysis for systolic BP (SBP) (mm Hg) adjusting for age, sex, race, and poverty, fluoride in water (mg/L) was significant with a coefficient of -0.44 (p = 0.046) among adolescents (12-18 years). Additional adjustments for race, poverty, serum levels of cotinine, and BMI remained significant. While an inverse relationship was found in children (8-11 years), none were significant. Fluoride in plasma was not significant across all ages. The odds ratio of high BP for an increase in water fluoride also was not significant. CONCLUSIONS: Higher concentrations of fluoride in water were associated with low SBP only among adolescents. Fluoride alone cannot be responsible for BP as several biological metabolic processes may influence its physiological effects. Fluoride consumption should be considered in conjunction with these processes. IMPACT: The high fluoride in drinking water was statistically significantly associated with low systolic BP in children and adolescents. The odds ratio of high BP for an increase in fluoride in drinking water was not significant. Our study contributes to the existing literature by providing individualized data and results on an individual level.
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Hipertensión , Hipotensión , Humanos , Niño , Adolescente , Fluoruros , Presión Sanguínea , Encuestas NutricionalesRESUMEN
The development of rigid polyaromatic building blocks for narrowband violet fluorophores has received tremendous attention. Herein, we designed and synthesized two new triangle-shaped rigid building blocks, namely, 2,5-di-tert-butylindolo[3,2,1-jk]carbazole (tBuICz) and 2,11-di-tert-butylindolo[3,2,1-jk]carbazole-4-carbonitrile (tBuICzCN), and tethered them with different chromophores to yield a series of violet-blue fluorophores, viz., ICzTPA-ICzPICN, and studied their structure-function relationship. The appended chromophores and cyano unit played a vital role in controlling the optical and electrical properties of the compounds. Except triphenylamine-substituted derivatives, the compounds showed pure violet emission (λem ≤ 403 nm). Intriguingly, the compounds exhibited narrow-band emission with a full-width at half-maximum ≤ 40 nm, attributed to the rigidity of the ICz core. The emission of the compounds displayed positive solvatochromism, which is ascribed to the photoinduced intramolecular charge transfer in the excited state. The compounds revealed excellent thermal robustness with T5d ≥ 363 °C. The triphenylamine-featuring derivatives displayed a high-lying HOMO compared to their congeners due to their electron-rich nature. When we applied these materials in organic light-emitting diodes, ICzPI outperformed in the series with an EQEmax of 3.07% and a current efficiency of 1.04 cd/A. Notably, its CIEy â¼ 0.046 precisely matched with the Rec.2020 standard of deep-blue color (CIEy â¼ 0.046).
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BACKGROUND: The aim of this study was to examine the bidirectional relationship between depression and travel. METHOD: We analyzed 8524 participants' data obtained from the 2008 to 2016 waves of the Korean Longitudinal Study of Ageing, a prospective cohort study. Depression was diagnosed using the Center for Epidemiological Studies Depression Scale: 10-Items (CES-D10), with scores of 4 or higher indicating depression. We used a generalized estimating equation and a cross-lagged panel model for statistical analysis. RESULTS: Participants who had not traveled for one year had a 71% higher risk of suffering from depression in the following year than did those who had traveled [relative risk (RR) = 1.71, P < 0.001], and participants with depression had more than double the increased risk of not traveling than did those not currently suffering from depression (RR = 2.08, P < 0.001). The cross-lagged panel model confirmed the vicious cycle involving the amount of travel and score on the CES-D10; individuals who traveled more frequently were more likely to have lower scores on the CES-D10 (coefficient = - 0.04 to - 0.03, Ps < 0.01), and individuals with higher scores were less likely to travel (coefficient = - 0.06 to - 0.03, Ps < 0.01). CONCLUSIONS: The risk of depression increases for people who do not travel, and a reciprocal relationship exists between travel and depression.
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When we develop wearable assistive devices, comfort and support are two main issues that need to be considered. In conventional design approaches, the degree of freedom of the wearer's joint movements tends to be oversimplified. Accordingly, the wearer's motion becomes restrained and bone/ligament injuries might occur in case of an unexpected fall. To mitigate these issues, this paper proposes a novel joint link mechanism inspired by a human spine structure as well as functionalities. The key feature of the proposed spine-like joint link mechanism is that hemispherical blocks are concatenated via flexible synthetic fiber lines so that their concatenation stiffness can be adjusted according to a tensile force. This feature has a great potentiality for designing a wearable assistive device that can support aged people's sit-to-stand action or augment spinal motion by regulating the concatenation stiffness. In addition, the concatenated hemispherical blocks enable the wearer to move his/her joint with full freedom, which in turn increases the wearer's mobility and prevents joint misalignment. The experimental results with a testbed and a pilot wearer substantiated that the spine-like joint link mechanism can serve as a key component in the design of wearable assistive devices for better mobility.
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Dispositivos de Autoayuda , Dispositivos Electrónicos Vestibles , Accidentes por Caídas , Anciano , Femenino , Humanos , Masculino , Movimiento/fisiología , Columna VertebralRESUMEN
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-transcription polymerase chain reaction assays for 8 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, nonenveloped 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 nonenveloped viruses persisted, suggesting that enhanced infection prevention strategies are required to mitigate spread of these viruses.
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COVID-19 , Distanciamiento Físico , Infecciones del Sistema Respiratorio , Adenoviridae , COVID-19/prevención & control , Bocavirus Humano , Humanos , Metapneumovirus , Orthomyxoviridae , República de Corea/epidemiología , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2RESUMEN
Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum-endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (Nâ =â 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.
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Anticuerpos Antihelmínticos , Schistosoma japonicum , Esquistosomiasis Japónica , Vacunas , Animales , Anticuerpos Antihelmínticos/inmunología , Resistencia a la Enfermedad , Humanos , Recurrencia Local de Neoplasia , Praziquantel/uso terapéutico , Proteoma , Reinfección/prevención & control , Schistosoma japonicum/genética , Esquistosomiasis Japónica/prevención & controlRESUMEN
INTRODUCTION: Disadvantaged and minority youth with type 1 diabetes are less likely to be on insulin pump therapy compared to the majority population. Little is known about how pediatric endocrinology providers determine eligibility for insulin pump. We aimed to identify provider factors influencing the decision to initiate insulin pump therapy. METHODS: We conducted a survey of Pediatric Endocrine Society members who prescribe insulin pump therapy to pediatric patients with type 1 diabetes. The survey collected information about prescriber characteristics, use and adherence to guidelines, eligibility criteria, and objective and subjective factors that influence insulin pump prescription. RESULTS: The survey was completed by 192 individuals who met eligibility criteria (14.1% response rate). The majority of respondents were attending providers, and were white, non-Hispanic females. A minority of providers (22%) reported following written insulin pump guidelines, and many (70%) reported using personal guidelines to guide patient selection. Most providers had no objective eligibility criteria, aside from standard glucose monitoring. Providers identified patient lifestyle and increased risk of hypoglycemia, as well as patient and family factors such as motivation, realistic expectations of insulin pump use, ability to demonstrate carbohydrate counting, patient request, and ability to communicate as important in the decision to initiate insulin pump. CONCLUSION: Pediatric endocrinology providers place significant importance on subjective factors and utilize few objective criteria in determining eligibility for insulin pump. In the setting of the known disparities in insulin pump use, providers should utilize objective, consistent criteria to determine which patients are safe to initiate insulin pump.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Adulto , Automonitorización de la Glucosa Sanguínea/economía , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/economía , Endocrinología/estadística & datos numéricos , Femenino , Humanos , Insulina/economía , Sistemas de Infusión de Insulina/economía , Sistemas de Infusión de Insulina/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pediatría/estadística & datos numéricos , Relaciones Médico-Paciente , Autoinforme , Encuestas y CuestionariosRESUMEN
BACKGROUND: The purpose of this study was to investigate the association between serum folate concentration and health-related quality of life (HRQOL) among the elderly in South Korea. MATERIALS AND METHODS: The data used in this study were drawn from 1,021 participants over 65 years old in the Korea National Health and Nutrition Examination Survey from 2016-2018. HRQOL was measured by the EQ-5D questionnaire. Participants were divided into tertiles of folate concentration (ranges 1.7-5.6, 5.7-9.4, and 9.5-31.9 ng/mL). We performed multivariable linear regression to examine the relationship between folate and HRQOL, and multivariable logistic regression to examine the relationship between folate and the dimensional problem of HRQOL. RESULTS: Higher folate concentrations were significantly associated with higher HRQOL in the elderly. The average HRQOL score of the elderly in the highest tertile of the folate level was 0.0289 higher than that of the lowest tertile (coefficient: 0.0289; 95% CI 0.0016, 0.0563). The HRQOL score increased by 0.0174 points when the folate concentration increased by 100%. When analyzing specific dimensions, a significant association with folate concentration was found only for the self-care dimension of HRQOL (odds ratio for self-care problems: 0.63; 95% CI 0.41, 0.99). CONCLUSIONS: The elderly with higher serum folate concentration tended to have higher HRQOL. Among HRQOL dimensions, self-care was only significantly associated with folate concentration.
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Ácido Fólico , Calidad de Vida , Anciano , Humanos , Encuestas Nutricionales , República de CoreaRESUMEN
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.
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Número de Embarazos , Transmisión Vertical de Enfermedad Infecciosa , Malaria/transmisión , Femenino , Humanos , Lactante , Parasitemia , Placenta/parasitología , Embarazo , Factores de RiesgoRESUMEN
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.
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Artritis Infecciosa , Osteomielitis , Absceso , Enfermedad Aguda , Niño , Humanos , Osteomielitis/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aimed to examine the relationship between working hours and health-related quality of life (HRQOL) in men and to determine whether this relationship was mediated by sleep duration and self-rated health (SRH). MATERIALS AND METHODS: Our study population included 2141 working men aged 20 to 49 years old from the Korea National Health and Nutrition Examination Survey 2016-2017. Working hours, SRH, and HRQOL were measured by a structured questionnaire survey. Sleep duration was calculated based on self-reported data. We investigated the association between working hours and HRQOL and performed a mediation analysis to evaluate the contributions of sleep duration and poor SRH to this relationship. RESULTS: This study identified a significant association between working hours and HRQOL. Long working hours directly and indirectly affected HRQOL through poor SRH. Men who overworked were more likely to report poor HRQOL due to worsened SRH. Poor SRH was responsible for 26.3% of this relationship. But sleep duration did not explain the relationship between working hours and HRQOL. CONCLUSIONS: Working hours were directly associated with HRQOL in men. Furthermore, there was an indirect effect of working hours on HRQOL mediated by poorer SRH. An improved work-life balance is necessary to promote men's health and quality of life.
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Estado de Salud , Calidad de Vida , Sueño , Equilibrio entre Vida Personal y Laboral , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , República de Corea , Autoinforme , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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.
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Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Sangre Fetal/inmunología , Inmunidad Materno-Adquirida , Malaria Falciparum/prevención & control , Proteínas Protozoarias/inmunología , Índice de Severidad de la Enfermedad , Animales , Antígenos de Protozoos/administración & dosificación , Estudios de Cohortes , Resistencia a la Enfermedad , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , Recién Nacido , Malaria Falciparum/inmunología , Ratones , Ratones Endogámicos BALB C , Parasitemia/inmunología , Parasitemia/prevención & control , Plasmodium berghei/inmunología , Plasmodium falciparum , Proteínas Protozoarias/administración & dosificación , Tanzanía , VacunaciónRESUMEN
BACKGROUND: Infection with the protozoan parasite Babesia, the causative agent of babesiosis, can result in asymptomatic to life-threatening illness. Severe cases of babesiosis are characterized by high levels of parasitemia (>4%-10%) and commonly treated with adjunctive red blood cell exchange (RCE) in addition to antimicrobial therapy. The efficacy of RCE in this context is unknown. STUDY DESIGN AND METHODS: Blood bank records were examined for requests for RCE during a 10-year period from 2007 to 2017. Relevant clinical and laboratory variables were extracted from medical records from presentation to 35 days after RCE and analyzed in univariate and multivariate models. RESULTS: Nineteen cases of babesiosis were identified in which RCE was performed. The median age of patients was 77 years, 74% of whom were male. A total of 37% of patients were asplenic. RCE was performed on average 1.3 days after presentation, with procedural urgency driven mainly by the level of parasitemia. Mean pre- and post-RCE levels of parasitemia were 12.9 and 3.4%, respectively, resulting in a mean percent reduction in parasitemia of 75%. Preprocedural parasitemia (p = 0.047) and age (p = 0.028) were both significant predictors of postprocedural hospital length of stay (post-RCE LOS). Neither postprocedural parasitemia (p = 0.12) nor percent reduction in parasitemia (p = 0.72) correlated with post-RCE LOS. Four patients died, none of whom were asplenic. Mortality was not correlated with hematologic, parasitologic, or clinical variables analyzed. CONCLUSIONS: Reduction in the level of parasitemia is the only known benefit of RCE in severe babesiosis.
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Babesia , Babesiosis/terapia , Transfusión de Eritrocitos , Parasitemia/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: We evaluated the association between etiology of maternal anemia and iron status throughout infancy. METHODS: Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated. RESULTS: Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status. CONCLUSIONS: Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.
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Anemia/diagnóstico , Anemia/genética , Hierro/sangre , Complicaciones Hematológicas del Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Esquistosomiasis/tratamiento farmacológico , Antihelmínticos/efectos adversos , Antihelmínticos/farmacología , Antígenos CD/sangre , Proteína C-Reactiva/análisis , Femenino , Ferritinas/sangre , Hemoglobinas/análisis , Hepcidinas/sangre , Humanos , Recién Nacido , Enfermedades del Recién Nacido , Interleucina-6/sangre , Deficiencias de Hierro , Masculino , Exposición Materna , Filipinas , Praziquantel/efectos adversos , Praziquantel/farmacología , Embarazo , Resultado del Embarazo , Receptores de Transferrina/sangre , Esquistosomiasis/complicacionesRESUMEN
Background: Follicular helper T cells (TFH) are specialized CD4 T cells required for B-cell help and antibody production. Methods: Given the postulated role of immune activation in dengue disease, we measured the expansion and activation of TFH in the circulation (peripheral TFH [pTFH]) collected from Thai children with laboratory-confirmed acute dengue virus (DENV) infection. Results: We found significant expansion and activation of pTFH subsets during acute infection with the highest frequencies of activated pTFH (PD1hi pTFH and PD1+CD38+ pTFH) detected during the critical phase of illness. Numbers of activated pTFH were higher in patients with secondary compared with primary infections and in patients with more severe disease. We also found a positive correlation between the frequencies of activated pTFH and the frequencies of plasmablasts. Conclusions: To our knowledge, this is the first ex vivo analysis of pTFH activation during acute DENV infection. Overall, our study supports the model that pTFH contribute to disease evolution during the critical stage of illness.
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Virus del Dengue/inmunología , Dengue/inmunología , Interacciones Huésped-Patógeno/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Enfermedad Aguda , Adolescente , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Niño , Preescolar , Humanos , LactanteRESUMEN
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.
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Anticuerpos Antiprotozoarios/inmunología , Susceptibilidad a Enfermedades/inmunología , Malaria Falciparum , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/metabolismo , Niño , Humanos , Estadios del Ciclo de Vida/inmunología , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Carga de Parásitos , Fosfoproteínas/genética , Fosfoproteínas/inmunología , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Proteínas Protozoarias/genética , Adulto JovenRESUMEN
Background: To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. Objectives: The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. Methods: We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin <30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin ≥30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. Results: Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 µg/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 µg/L; P = 0.042). Conclusions: Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy. This trial was registered at www.clinicaltrials.gov as NCT00486863.