RESUMEN
Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.
RESUMEN
In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.
Asunto(s)
Citocinas/metabolismo , Inmunidad Materno-Adquirida , Praziquantel/administración & dosificación , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Esquistosomiasis Japónica/tratamiento farmacológico , Animales , Antiprotozoarios/administración & dosificación , Niño , Estudios de Cohortes , Citocinas/sangre , Método Doble Ciego , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Modelos Lineales , Masculino , Análisis Multivariante , Filipinas , Embarazo , Complicaciones Parasitarias del Embarazo/inmunología , Schistosoma japonicum/efectos de los fármacos , Esquistosomiasis Japónica/inmunología , Resultado del TratamientoRESUMEN
An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with S. japonicum in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women (n = 15 each) and lactating postpartum women (n = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC0-24) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis.
Asunto(s)
Antihelmínticos , Schistosoma japonicum , Esquistosomiasis , Animales , Antihelmínticos/uso terapéutico , Femenino , Humanos , Lactancia , Filipinas , Praziquantel/uso terapéutico , Embarazo , Schistosoma mansoni , Esquistosomiasis/tratamiento farmacológicoRESUMEN
BACKGROUND: The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. METHODS/FINDINGS: This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks' gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks' gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. CONCLUSIONS: Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ClinicalTrials.gov (NCT00486863).
Asunto(s)
Antihelmínticos/administración & dosificación , Citocinas/sangre , Sangre Fetal/química , Placenta/patología , Praziquantel/administración & dosificación , Complicaciones Parasitarias del Embarazo/patología , Esquistosomiasis Japónica/patología , Adulto , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Filipinas , Embarazo , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Esquistosomiasis Japónica/complicaciones , Esquistosomiasis Japónica/tratamiento farmacológico , Adulto JovenRESUMEN
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.
Asunto(s)
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
Low- and middle-income countries (LMICs) carry a high burden of infectious diseases associated with impaired gut integrity, leading to microbial translocation. Pregnancies in this setting are at high risk of fetal growth restriction (FGR). We examined the association among specific risk factors for impaired gut integrity (schistosomiasis, hookworm infection, and alcohol consumption), blood endotoxin levels, and FGR. Endotoxins, lipopolysaccharide-binding proteins (LBPs), and cytokines were measured in blood from women at 32 weeks gestation, the maternal-fetal interface (MFI) at delivery, and cord blood at delivery. Resolution of schistosomiasis had no impact on endotoxin levels; however, maternal hookworm infection and alcohol consumption were associated with modest increases in endotoxin at the MFI. Cytokines responses within the maternal peripheral blood and blood from the MFI were positively associated with endotoxins, but many cord blood cytokines were negatively associated with endotoxins. Newborns with FGR also had higher levels of endotoxins at the MFI. Risk factors for microbial translocation may lead to increased levels of endotoxins at the MFI, which may contribute to poor growth in utero.
Asunto(s)
Endotoxinas/sangre , Sangre Fetal/química , Tracto Gastrointestinal/parasitología , Intercambio Materno-Fetal , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Traslocación Bacteriana , Proteínas Portadoras/sangre , Estudios de Cohortes , Citocinas/sangre , Femenino , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/etiología , Edad Gestacional , Recursos en Salud , Infecciones por Uncinaria/complicaciones , Humanos , Recién Nacido , Filipinas/epidemiología , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Esquistosomiasis/complicaciones , Esquistosomiasis/epidemiologíaRESUMEN
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.
Asunto(s)
Anemia/etiología , Ferritinas/sangre , Hepcidinas/sangre , Salud del Lactante , Inflamación/complicaciones , Hierro/sangre , Complicaciones del Embarazo/sangre , Adulto , Anemia/sangre , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Animales , Área Bajo la Curva , Biomarcadores/sangre , Femenino , Edad Gestacional , Humanos , Recién Nacido , Inflamación/sangre , Deficiencias de Hierro , Madres , Estado Nutricional , Embarazo , Complicaciones del Embarazo/etiología , Receptores de Transferrina/sangre , Valores de Referencia , Factores de Riesgo , Schistosoma japonicum , Adulto JovenRESUMEN
The parasitic zoonoses cysticercosis/taeniasis is among the 17 major Neglected Tropical Diseases (NTDs) identified by the WHO as a focus for research and control. It is caused by a larval stage (cysticercus) infection of Taenia solium tapeworm in both humans and pigs. Cysticercosis occurs in many resource-poor countries, especially those with warm and mild climates in the regions of Latin America (LA), Asia and Sub-Saharan Africa (SSA). The prevalence of human cysticercosis is marked in those areas where individuals are traditionally keen to consume raw or insufficiently cooked pork and/or where the husbandry of pigs is improper. The worldwide burden of cysticercosis is unclear and notably, large-scale control initiatives are lacking in all regions. This review focuses on the current endemic status of cysticercosis caused by T. solium infection in both humans and pigs living in 13 Southeast Asian countries. We will also emphasize epidemiological data as well as prevention and control of human neurocysticercosis.
Asunto(s)
Crianza de Animales Domésticos/normas , Enfermedades Transmisibles Emergentes/parasitología , Cisticercosis/epidemiología , Carne Roja/parasitología , Sus scrofa/parasitología , Enfermedades de los Porcinos/parasitología , Taenia solium/aislamiento & purificación , Animales , Anticestodos/uso terapéutico , Asia Sudoriental/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/prevención & control , Cisticercosis/prevención & control , Cisticercosis/veterinaria , Humanos , Prevalencia , Salud Pública , Porcinos , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/prevención & control , Zoonosis/epidemiologíaRESUMEN
OBJECTIVE: To identify pathways through which pre- and postnatal factors directly or indirectly affect infant neurodevelopment at 12 months of age among Filipino infants. METHODS: The Bayley Scales of Infant Development, third edition was used to assess the development of 314 infants of mothers enrolled in a trial examining the safety and efficacy of praziquantel during pregnancy. Maternal covariates included socioeconomic status, iron and nutritional status, cognitive performance, and alcohol intake. Infant covariates included birth weight and feeding practices, longitudinal growth and nutritional status, hemoglobin and iron status captured at birth, and 6 and 12 months of age. Multivariable regression and structural equation modeling were used to identify significant factors associated with infant development. RESULTS: In regression models, maternal education, cognition, and iron status as well as infant weight-for-age z-score (WAZ), weight-for-length z-score, and WAZ gains were significantly associated with infant development at 12 months of age. Structural equation modeling demonstrated a direct effect of maternal cognition on most subscales of infant development and indirect effects on expressive language through effects on infant WAZ. Maternal iron status was a stronger predictor of infant cognition subscale scores than was infant iron status. Exclusive breastfeeding had a direct influence on expressive language rather than acting through improved infant iron or nutritional status. CONCLUSIONS: We identified key modifiable risk factors for impaired neurodevelopment, including prenatal risk factors such as maternal iron status. Integrated nutritional interventions that impact both maternal and infant nutritional status are likely to positively affect infant neurodevelopment through identified pathways.
Asunto(s)
Desarrollo Infantil , Trastornos del Neurodesarrollo/etiología , Adulto , Cognición , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Madres , Estado Nutricional , Filipinas , Embarazo , Factores de RiesgoRESUMEN
CLINICAL TRIAL REGISTRATION: NCT00486863.
Asunto(s)
Crecimiento y Desarrollo , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Estado Nutricional/fisiología , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Modelos Biológicos , Análisis Multivariante , Filipinas , DelgadezRESUMEN
The overall aims of this project are to assess the safety and immunogenicity of the Schistosoma japonicum vaccine paramyosin among water buffaloes residing in endemic areas. The study was conducted in four villages in Leyte, the Philippines, an area highly endemic for schistosomiasis japonica. One hundred and fifteen (N=115) animals provided baseline stool samples for coprologic examination, with preliminary results using FLOTAC showing a 10% prevalence of schistosomiasis. Forty-nine (N=49) animals consented to treatment with 25 mg/kg Praziquantel, and 40, 36 and 32 animals consented to the first, second and third dose of the paramyosin vaccine, respectively. The safety trial involved the first 20 animals and included skin testing, vaccination, anaphylaxis monitoring, as well as hematology and serum chemistry analysis. Skin tests revealed that only three out of 20 animals exhibited redness at the injection site, with none greater than 1 cm. None of the animals exhibited anaphylaxis, and all hematology and serum chemistry markers were within normal range or were similar to pre-vaccination levels. None of the 40 animals administered with the first dose exhibited anaphylaxis, nor any of the subsequent vaccine doses. Immunogenicity assessment of sera collected prior to every vaccination and one month after the last dose showed that the paramyosin vaccine induced robust antibody responses to all animals, as assessed by ELISA. The cytokine levels of whole blood culture supernatants will be further assessed. Our findings demonstrate that the S. japonicum paramyosin vaccine is a safe, well-tolerated and immunogenic treatment among water buffalos residing in endemic areas.
Asunto(s)
Búfalos , Proteínas Recombinantes/inmunología , Schistosoma japonicum/metabolismo , Esquistosomiasis Japónica/veterinaria , Tropomiosina/inmunología , Vacunas/inmunología , Animales , Antihelmínticos/farmacología , Heces/parasitología , Praziquantel/farmacología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/prevención & control , Tropomiosina/genética , Tropomiosina/metabolismoRESUMEN
BACKGROUND: Despite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of this study were to assess whether treatment of pregnant women with schistosomiasis at 12-16 weeks gestation leads to improved maternal and newborn outcomes and to collect maternal and newborn safety data. METHODS: This phase 2, randomised, double-blind, placebo-controlled trial was done in 72 baranguays (villages) serviced by six municipal health centres in a schistosomiasis endemic region of northeastern Leyte, Philippines. Pregnant women (at 12-16 weeks gestation) who were otherwise healthy but infected with Schistosoma japonicum were enrolled and randomly assigned (1:1) to receive either over-encapsulated praziquantel (total dose 60 mg/kg given as two split doses) or placebo. Participants, investigators, midwives, and laboratory staff were all masked to treatment. The primary outcome was birthweight. Safety data were collected including immediate reactogenicity, post-dosing toxicology ascertained 24 h after study drug administration, and maternal and newborn serious adverse events. Analysis followed the intention-to-treat principle. Analyses were done using hierarchical generalised linear models to adjust for identified confounders and account for potential clustering of observations within villages and municipalities. This trial is registered with ClinicalTrials.gov, number NCT00486863. FINDINGS: Between Aug 13, 2007, and Dec 3, 2012, 370 pregnant women were enrolled and randomly assigned to each treatment group (184 to the placebo group, 186 to the praziquantel group). Most women had low-intensity infections (n=334, 90%). Treatment with praziquantel did not have a significant effect on birthweight (2·85 kg in both groups, ß=-0·002 [95% CI -0·088 to 0·083]; p=0·962). Treatment was well tolerated with reactogenicity rates similar to those seen in non-pregnant participants (severe reactions occurred in five patients in the praziquantel group and two in the placebo group, and included headache, fever, and malaise). There were no significant differences in key safety outcomes including abortion, fetal death in utero, and congenital anomalies. INTERPRETATION: Results from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO. FUNDING: National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).
Asunto(s)
Antihelmínticos/administración & dosificación , Antihelmínticos/efectos adversos , Peso al Nacer/efectos de los fármacos , Feto/efectos de los fármacos , Praziquantel/administración & dosificación , Praziquantel/efectos adversos , Esquistosomiasis/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Edad Gestacional , Humanos , Recién Nacido , Filipinas , Embarazo , Adulto JovenRESUMEN
The global socioeconomic importance of helminth parasitic disease is underpinned by the considerable clinical impact on millions of people. While helminth polyparasitism is considered common in the Philippines, little has been done to survey its extent in endemic communities. High morphological similarity of eggs between related species complicates conventional microscopic diagnostic methods which are known to lack sensitivity, particularly in low intensity infections. Multiplex quantitative PCR diagnostic methods can provide rapid, simultaneous identification of multiple helminth species from a single stool sample. We describe a multiplex assay for the differentiation of Ascaris lumbricoides, Necator americanus, Ancylostoma, Taenia saginata and Taenia solium, building on our previously published findings for Schistosoma japonicum. Of 545 human faecal samples examined, 46.6% were positive for at least three different parasite species. High prevalences of S. japonicum (90.64%), A. lumbricoides (58.17%), T. saginata (42.57%) and A. duodenale (48.07%) were recorded. Neither T. solium nor N. americanus were found to be present. The utility of molecular diagnostic methods for monitoring helminth parasite prevalence provides new information on the extent of polyparasitism in the Philippines municipality of Palapag. These methods and findings have potential global implications for the monitoring of neglected tropical diseases and control measures.
Asunto(s)
Helmintiasis/epidemiología , Helmintiasis/parasitología , Parasitosis Intestinales/parasitología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adolescente , Adulto , Animales , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Parasitosis Intestinales/epidemiología , Masculino , Persona de Mediana Edad , Filipinas/epidemiología , Adulto JovenRESUMEN
The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis) have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD) technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle) from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively) and carabao (80.00% and 55.24%, respectively). The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively). The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines.
Asunto(s)
Enfermedades de los Bovinos/epidemiología , Fasciola/aislamiento & purificación , Fascioliasis/veterinaria , Schistosoma japonicum/aislamiento & purificación , Esquistosomiasis Japónica/veterinaria , Zoonosis/epidemiología , Animales , Búfalos/parasitología , Bovinos , Enfermedades de los Bovinos/transmisión , China/epidemiología , Fascioliasis/epidemiología , Fascioliasis/transmisión , Heces/parasitología , Humanos , Filipinas/epidemiología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Esquistosomiasis Japónica/epidemiología , Esquistosomiasis Japónica/transmisión , Zoonosis/parasitología , Zoonosis/transmisiónRESUMEN
BACKGROUND: The Philippines has a population of approximately 103 million people, of which 6.7 million live in schistosomiasis-endemic areas with 1.8 million people being at risk of infection with Schistosoma japonicum. Although the country-wide prevalence of schistosomiasis japonica in the Philippines is relatively low, the prevalence of schistosomiasis can be high, approaching 65% in some endemic areas. Of the currently available microscopy-based diagnostic techniques for detecting schistosome infections in the Philippines and elsewhere, most exhibit varying diagnostic performances, with the Kato-Katz (KK) method having particularly poor sensitivity for detecting low intensity infections. This suggests that the actual prevalence of schistosomiasis japonica may be much higher than previous reports have indicated. METHODOLOGY/PRINCIPAL FINDINGS: Six barangay (villages) were selected to determine the prevalence of S. japonicum in humans in the municipality of Palapag, Northern Samar. Fecal samples were collected from 560 humans and examined by the KK method and a validated real-time PCR (qPCR) assay. A high S. japonicum prevalence (90.2%) was revealed using qPCR whereas the KK method indicated a lower prevalence (22.9%). The geometric mean eggs per gram (GMEPG) determined by the qPCR was 36.5 and 11.5 by the KK. These results, particularly those obtained by the qPCR, indicate that the prevalence of schistosomiasis in this region of the Philippines is much higher than historically reported. CONCLUSIONS/SIGNIFICANCE: Despite being more expensive, qPCR can complement the KK procedure, particularly for surveillance and monitoring of areas where extensive schistosomiasis control has led to low prevalence and intensity infections and where schistosomiasis elimination is on the horizon, as for example in southern China.
Asunto(s)
Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Esquistosomiasis Japónica/epidemiología , Adolescente , Adulto , Anciano , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Filipinas/epidemiología , Prevalencia , Esquistosomiasis Japónica/prevención & controlRESUMEN
Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-γ producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later.
RESUMEN
Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.
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Adiposidad , Modelos Estadísticos , Dengue Grave/epidemiología , Dengue Grave/metabolismo , Adulto , AMP Cíclico/metabolismo , Humanos , Lactante , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Leptina/sangre , Masculino , Desnutrición/metabolismo , Desnutrición/virología , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Riesgo , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 8/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Infants have long been known to have higher infectious diseases morbidity and mortality and suboptimal vaccination responses compared to older children and adults. A variety of differences in innate and adaptive immune responses have been described between these two groups. We compared Toll-like receptor (TLR)-induced production of pro-interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α between 2-month-old infants and adults. TLR 7/8-induced production of pro-IL-1ß and IL-6 in monocytes was lower in 2-month-old infants compared to adults. There was no difference in TLR 7/8-induced production of TNF-α. Lower TLR-induced production of pro-IL-1ß and IL-6 in innate immune cells during early infancy likely contributes to suboptimal vaccine responses and infectious diseases susceptibility.
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Interleucina-1beta/sangre , Interleucina-6/sangre , Monocitos/metabolismo , Receptores Toll-Like/sangre , Receptores Toll-Like/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Adulto , Femenino , Citometría de Flujo , Humanos , Lactante , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 8/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The two-domain taurocyamine kinase (TK) from Paragonimus westermani was suggested to have a unique substrate binding mechanism. We performed site-directed mutagenesis on each domain of this TK and compared the kinetic parameters Km(Tc) and Vmax with that of the wild-type to determine putative amino acids involved in substrate recognition and binding. Replacement of Y84 on domain 1 and Y87 on domain 2 with R resulted in the loss of activity for the substrate taurocyamine. Y84E mutant has a dramatic decrease in affinity and activity for taurocyamine while Y87E has completely lost catalytic activity. Substituting H and I on the said positions also resulted in significant changes in activity. Mutation of the residues A59 on the GS region of domain 1 also caused significant decrease in affinity and activity while mutation on the equivalent position on domain 2 resulted in complete loss of activity.
Asunto(s)
Paragonimus westermani/enzimología , Fosfotransferasas (Aceptor del Grupo Nitrogenado)/metabolismo , Estructura Terciaria de Proteína , Taurina/análogos & derivados , Tirosina , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Secuencia Conservada , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Fosfotransferasas (Aceptor del Grupo Nitrogenado)/química , Fosfotransferasas (Aceptor del Grupo Nitrogenado)/genética , Estructura Terciaria de Proteína/genética , Alineación de Secuencia , Especificidad por Sustrato , Taurina/metabolismo , Tirosina/química , Tirosina/genéticaRESUMEN
Taurocyamine kinase (TK) is an enzyme that catalyzes the reversible transfer of a phosphate between ATP and taurocyamine. Annelid TKs were suggested to have evolved from a CK ancestor. However, TKs from the lung fluke Paragonimus westermani comprised another lineage. Construction of phylogenetic tree and comparison of exon/intron organization showed that P. westermani TK and other trematode TKs evolved from a molluscan arginine kinase (AK) gene. Exon shuffling probably caused the changes in amino acid sequence thereby changing the affinity from AK to TK. The present study provides new insights on the evolution of phosphagen kinases found in trematodes.