RESUMEN
BACKGROUND: Pneumonia is the leading cause of childhood mortality globally. Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia. Maternal serum antibody protects infants from RSV disease. The objective of our study was to characterize RSV antibody levels in mother-infant pairs. METHODS: Serial serum samples were collected from mother-infant pairs in Bangladesh from the third trimester of pregnancy to 72 weeks postpartum and tested using an RSV antibody microneutralization assay. Serologic infection was defined as a 4-fold increase in antibody titer. Maternal antibody half-life was calculated using infant antibody titers from birth to 20 weeks. RESULTS: The ratio of infant cord blood to maternal serum RSV antibody titers in 149 mother-infant pairs was 1.01 (95% confidence interval [CI], .99-1.03). Maternal RSV antibody titers in the third trimester and at birth were strongly correlated (R = 0.68). Antibody half-life was 38 days (95% CI, 36-42 days). Higher cord blood RSV antibody titers were associated with a lower risk of serologic infection (P = .01) and maintenance of antibody titer above a potentially protective threshold (P < .001). CONCLUSIONS: Efficient transplacental transfer of RSV-specific antibody from mother to the fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody titers were associated with protection from serologic infection.
Asunto(s)
Anticuerpos Antivirales/sangre , Inmunidad Materno-Adquirida , Intercambio Materno-Fetal , Virus Sincitial Respiratorio Humano/inmunología , Adolescente , Bangladesh , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Periodo Periparto , Embarazo , Adulto JovenRESUMEN
Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatment-based control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n = 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P = 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n = 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n = 274), even after adjusting for potential confounders (P = 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.
Asunto(s)
Antígenos Helmínticos/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Esquistosomiasis Japónica/prevención & control , Tropomiosina/inmunología , Adolescente , Adulto , Anciano , Animales , Antihelmínticos/uso terapéutico , Niño , Heces/parasitología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Filipinas , Praziquantel/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: In communities where Schistosoma species are endemic, the prevalence and intensity of schistosomiasis is disproportionately high among children, compared with adults. This epidemiologic pattern is consistent with either the slow development of resistance or the requirement of host developmental changes for the expression of resistance. METHODS: We enrolled 87 individuals aged 7-18 years who did not have Schistosoma japonicum infection and 641 individuals aged 7-30 years with S. japonicum infection, all of whom reside in 3 villages in Leyte, Philippines. At baseline, S. japonicum infection was assessed by Kato-Katz thick-smear stool examination, and the levels of the pubertal hormone dehydroepiandrosterone sulfate (DHEA-S) in serum were determined. Individuals with S. japonicum infection were treated with praziquantel, after which stool examination and DHEA-S level measurement were performed every 3 months for 18 months. RESULTS: In cross-sectional analyses, the intensity of infection among individuals with high DHEA-S levels was 43% lower (28 eggs per g, n = 243), compared with individuals with low DHEA-S levels (50 eggs per g, n = 242), even after adjusting for age, sex, and village (P = .01). Following praziquantel treatment, increased DHEA-S levels were associated with resistance to reinfection (P = .006). The intensity of reinfection among individuals with high DHEA-S levels was 42% lower, compared with individuals with low DHEA-S levels, even after adjusting for age, baseline intensity of S. japonicum infection, village, sex and water contact (P < .001). CONCLUSIONS: Increased DHEA-S levels in serum, a marker for adrenal development, is associated with reduced S. japonicum infection and reinfection, even after adjusting for age and, by proxy, cumulative exposure. These data suggest that an intrinsic property of host pubertal development mediates, in part, the resistance to infection observed in older individuals.
Asunto(s)
Pubertad/fisiología , Esquistosomiasis Japónica/diagnóstico , Adolescente , Adulto , Envejecimiento , Antihelmínticos/uso terapéutico , Niño , Sulfato de Deshidroepiandrosterona/sangre , Heces/parasitología , Femenino , Humanos , Inmunidad Innata , Masculino , Recuento de Huevos de Parásitos , Praziquantel/uso terapéutico , Pubertad/sangre , Esquistosomiasis Japónica/tratamiento farmacológicoRESUMEN
BACKGROUND: Observational and interventional evidence supports a relation between human schistosomiasis and anemia; however, the exact causal mechanisms remain unclear. Eggs translocating across the intestinal or bladder wall may result in extracorporeal blood loss with subsequent iron deficiency. Alternatively, anemia may result from cytokine-mediated dyserythropoiesis, as seen in anemia of inflammation. OBJECTIVES: By evaluating the cross-sectional relation between the intensity of Schistosoma japonicum infection, hemoglobin concentration, and iron status in 7-30-y-old persons from S. japonicum-endemic rice-farming villages in the province of Leyte, Philippines, we assessed the relative contribution of iron deficiency and anemia of inflammation to schistosomiasis-associated anemia. DESIGN: We enrolled 627 S. japonicum-infected and 111 S. japonicum-uninfected persons. We obtained stool samples to quantify S. japonicum infection and venous blood samples for hemograms and measures of iron status and inflammation. RESULTS: Intensity of S. japonicum infection was independently associated with hemoglobin (beta = -0.24; 95% CI: -0.31, -0.17). Persons with high-intensity infection had a greater risk of iron deficiency anemia (adjusted prevalence odds ratio: 6.6; 95% CI: 2.9, 14.7), but there was no evidence of this relation in low-intensity infections. In contrast, anemia without iron deficiency was prevalent across all intensities (adjusted prevalence odds ratio: 3.8; 95% CI: 1.5, 9.5). CONCLUSIONS: Storage iron deficiency is a major contributor to anemia in high-intensity S. japonicum infection. A high prevalence of anemia without iron deficiency, exclusion of other mechanisms of anemia, and the evidence of low bioavailable iron suggest that anemia of inflammation contributes to S. japonicum-associated anemia at all infection intensities.
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Anemia Ferropénica/epidemiología , Anemia/epidemiología , Hemoglobinas/análisis , Esquistosomiasis Japónica/complicaciones , Adolescente , Adulto , Anemia/sangre , Anemia/parasitología , Anemia Ferropénica/sangre , Anemia Ferropénica/parasitología , Niño , Intervalos de Confianza , Estudios Transversales , Enfermedades Endémicas , Heces/parasitología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Oportunidad Relativa , Recuento de Huevos de Parásitos , Filipinas/epidemiología , Receptores de Transferrina/sangre , Factores de Riesgo , Esquistosomiasis Japónica/sangre , Estudios Seroepidemiológicos , Índice de Severidad de la Enfermedad , Clase SocialRESUMEN
Schistosomiasis is associated with undernutrition, but the mechanisms involved remain unknown. We analyzed baseline and follow-up data from a longitudinal treatment-reinfection study in N = 477 Schistosoma japonicum-infected subjects 7-20 years of age from Leyte, the Philippines. After baseline treatment with praziquantel, follow-up visits were scheduled every 3 months for 18 months; stool, venous blood, and anthropometric measurements were collected at each visit. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with specific S. japonicum antigens was measured once 4 weeks after treatment. After adjustment for confounders, S. japonicum intensity was associated with decreased serum albumin and Z-scores (all P < 0.05) and with increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was associated with decreased albumin and Z-scores (all P < 0.01). Production of IL-1b and tumor necrosis factor (TNF)-alpha in response to worm antigen was associated with decreased albumin (both P < 0.005) and height-for-age Z-score (TNF-alpha only, P = 0.05). S. japonicum-associated undernutrition may, in part, result directly from inflammation.
Asunto(s)
Proteína C-Reactiva/análisis , Citocinas/sangre , Desnutrición/etiología , Esquistosomiasis Japónica/complicaciones , Adolescente , Adulto , Animales , Antihelmínticos/uso terapéutico , Niño , Heces/parasitología , Femenino , Humanos , Estudios Longitudinales , Masculino , Desnutrición/sangre , Desnutrición/inmunología , Evaluación Nutricional , Estado Nutricional , Recuento de Huevos de Parásitos , Praziquantel/uso terapéutico , Estudios Prospectivos , Recurrencia , Schistosoma japonicum/crecimiento & desarrollo , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/tratamiento farmacológico , Esquistosomiasis Japónica/inmunología , Albúmina Sérica/análisisRESUMEN
The objectives of this study were 1) to provide more accurate estimates of the relationship between Schistosoma japonicum infection and both protein energy malnutrition (PEM) and anemia through better adjustment for potential confounders such as socioeconomic status (SES) and geo-helminth infections and 2) to assess the role of occult blood loss in mediating S. japonicum-associated anemia. We examined cross-sectionally 729 individuals (86.7% S. japonicum-infected and 13.3% S. japonicum-uninfected) aged 7-30 years in Leyte, The Philippines. The main outcome measures were height-for-age Z-score (HAZ), body-mass-index Z-score (BMIZ), triceps skinfold Z-score, hemoglobin, and fecal occult blood loss. Multivariate models were created to assess the relationship between S. japonicum infection and nutritional status after adjusting for age, gender, other helminths, and SES. After controlling for confounders, intensity of S. japonicum infection was inversely related to hemoglobin in all age groups (P < 0.0001) and HAZ among children = 12 years (P = 0.03), but not to BMIZ (P = 0.52) or triceps skinfold Z-score (P = 0.11). Individuals with high-intensity S. japonicum infection were 3.5 times more likely to have occult blood in the stool. Adjustment for occult blood did not attenuate the relationship between S. japonicum and hemoglobin, suggesting other mechanisms are involved. Adjustment for SES allows more accurate assessment of the relationship between S. japonicum and both PEM and anemia. Exploration of the mechanisms of S. japonicum-associated anemia suggests that processes other than extracorporeal blood loss, such as anemia or inflammation, may be involved.
Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Estado Nutricional/fisiología , Esquistosomiasis Japónica/fisiopatología , Adolescente , Adulto , Anemia/parasitología , Niño , Estudios Transversales , Dieta , Heces/parasitología , Femenino , Trastornos del Crecimiento/parasitología , Humanos , Masculino , Recuento de Huevos de Parásitos , FilipinasRESUMEN
Schistosoma japonicum has been related to anemia, but the mechanisms mediating this relationship remain unresolved. The primary objective of this study was to assess the role of occult blood loss in mediating S. japonicum-associated anemia after adjusting for age, sex, socioeconomic status (SES), and other helminth infections. The secondary objective was to identify intensity categories of risk for occult blood loss for Trichuris and hookworm after adjustment for the presence of other helminth infections. The role of occult blood loss in mediating S. japonicum-associated anemia was studied cross-sectionally in 729 individuals 8-30 years old in Leyte, The Philippines. Three stool specimens were examined in duplicate for helminth eggs. Hemoglobin, fecal occult blood loss, and anemia were measured and related to the presence and intensity of helminths. Multivariate models were made to adjust for confounding by other helminths and SES. In multivariate models, hemoglobin significantly decreased with increasing infection intensity of S. japonicum, hookworm, and T. trichuria (P < 0.0031, P < 0.0001, and P < 0.0001, respectively). Individuals with higher intensities S. japonicum and T. trichuria were significantly more likely to be fecal occult positive (odds ratio [OR] = 3.54; P = 0.008 and OR = 2.68; P = 0.013, respectively), although this was not true for individuals with hookworm. Additionally, individuals with higher intensities of S. japonicum, hookworm, and T. trichuria were all more likely to be anemic (OR = 3.7, P = 0.0002; OR = 5.3, P = 0.0003; and OR = 1.6, P = 0.021, respectively). It is likely that occult blood loss plays a role only at heavier intensity S. japonicum infections and some other mechanism, such as anemia of inflammation, may be contributing to anemia.
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Anemia Ferropénica/epidemiología , Esquistosomiasis Japónica/epidemiología , Adolescente , Adulto , Anemia Ferropénica/etiología , Anemia Ferropénica/parasitología , Animales , Ascaris/aislamiento & purificación , Niño , Estudios Transversales , Enfermedades Endémicas , Heces/parasitología , Femenino , Helmintiasis/complicaciones , Helmintiasis/epidemiología , Helmintiasis/parasitología , Humanos , Masculino , Necator/aislamiento & purificación , Sangre Oculta , Filipinas/epidemiología , Prevalencia , Factores de Riesgo , Schistosoma japonicum/aislamiento & purificación , Esquistosomiasis Japónica/complicaciones , Esquistosomiasis Japónica/parasitología , Factores Socioeconómicos , Trichuris/aislamiento & purificaciónRESUMEN
The objective of this study was to examine the independent effect of infection with each of four helminths (Ascaris lumbricoides, Schistosoma japonicum, Necator americanus, and Trichuris trichiura) on cognitive function after adjusting for the potential confounders nutritional status, socioeconomic status (SES), hemoglobin, sex, and the presence of other helminthes. This cross-sectional study was carried out in a rural village in Leyte, The Philippines in 319 children 7-18 years old. Three stools were collected and read in duplicate by the Kato Katz method. Infection intensity was defined by World Health Organization criteria. Cognitive tests were culturally adapted and translated. Learning and memory cognitive domains were each defined by three subscales of the Wide Range Assessment of Memory and Learning, which had an inter-rater reliability >/= 0.92 and test-retest reliabilities ranging from 0.61 to 0.89. A household SES questionnaire was administered. A logistic regression model was used to quantify the association between performance in different cognitive domains (learning, memory, verbal fluency, and the Philippine Non-Verbal Intelligence Test) and helminth infections. After adjusting for age, sex, nutritional status, hemoglobin, and SES, S. japonicum infection was associated with poor performance on tests of learning (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 1.1-6.9), A. lumbricoides infection was associated with poor performance on tests of memory (OR = 2.2, 95% CI = 1.04-4.7), and T. trichiura infection was associated with poor performance on tests of verbal fluency (OR = 4.5, 95% CI = 1.04-30). Helminth infection was associated with lower performance in three of the four cognitive domains examined in this study. These relationships remained after rigorous control for other helminths and important confounding covariates.
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Fenómenos Fisiológicos Nutricionales Infantiles , Helmintiasis/epidemiología , Helmintiasis/fisiopatología , Discapacidades para el Aprendizaje/parasitología , Trastornos de la Memoria/parasitología , Trastornos del Habla/parasitología , Adolescente , Anemia/parasitología , Anemia/fisiopatología , Niño , Dieta , Femenino , Trastornos del Crecimiento/parasitología , Humanos , Masculino , Filipinas/epidemiología , Factores SocioeconómicosRESUMEN
BACKGROUND: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood deaths in most developing countries, including Nigeria. Vitamin D is associated with innate immunity and may play a role in the control of infections. Case-control studies, including a small study from Nigeria, show inconsistent results for the association between vitamin D status and risk of ALRTI. AIMS: To examine the relationship between vitamin D status and hospitalization for ALRTI in Nigerian children. METHODS: Fifty children aged 2-60 months hospitalised with ALRTI were studied prospectively. ALRTI was diagnosed on the basis of modified WHO criteria. Each patient was matched with controls for age and gender. The controls were enrolled either from children attending well-child clinics or general clinics without evidence of respiratory infection or admitted to the hospital for elective surgery. A structured questionnaire collected data on demography, health, diet, duration of exposure to sunlight and percentage of body surface exposed to sunlight (according to type of clothing) while outdoors, and potential risk factors for ALRTI. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured using a chemiluminescenceimmuno-assay. The differences between cases and controls in serum 25(OH)D concentrations, association between vitamin D status and ALRTI and risk factors for vitamin D deficiency were assessed. RESULTS: Mean (SD) 25(OH)D concentrations in patients and controls were similar [61·5 (25·8) vs 63·1 (22·9) nmol/L,Pâ=â0·95].25% of all 100 subjects studied had serum 25(OH)D<50 nmol/L. In a multiple conditional logistic regression model, only lower percentage of body surface area exposed to sunlight was associated with increased risk of ALRTI. The percentage of body surface area exposed to sunlight while outdoors (Pâ=â0·028) and vitamin D supplement use (Pâ=â0·009) were independent determinants of vitamin D deficiency in the overall study population. CONCLUSIONS: ALRTI was not associated with vitamin D status, but was associated with less exposure to sunlight. Exposure to sunlight and vitamin D supplementation contributed to vitamin D status in this population.
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Infecciones del Sistema Respiratorio/epidemiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/análogos & derivados , Estudios de Casos y Controles , Preescolar , Femenino , Hospitalización , Humanos , Lactante , Mediciones Luminiscentes , Masculino , Nigeria/epidemiología , Estudios Prospectivos , Exposición a la Radiación , Infecciones del Sistema Respiratorio/etiología , Suero/química , Luz Solar , Encuestas y Cuestionarios , Vitamina D/sangre , Deficiencia de Vitamina D/diagnósticoRESUMEN
Cysticercosis is a significant public health problem in countries where pigs are raised for consumption and remains an important cause of neurological disease worldwide. The Philippines is considered an endemic area for cysticercosis because cases in both humans and pigs have been reported; however, epidemiologic information stays limited. We conducted a pilot survey of the seroprevalence of human cysticercosis in a village in Leyte, the Philippines, by measuring antibody specific for Taenia solium cyst-fluid antigen. There were 497 subjects aged 7-30 years in our study and most subjects were infected with one or more helminths. The overall cysticercosis seroprevalence in this population was 24.6% (95% CI: 20.82% ~ 28.58%) with no significant difference based on age, sex, or other helminth coinfection status. Although the sample may not be representative of the whole community, the findings suggest that cysticercosis is a significant, but underrecognized public health concern in the Philippines.
RESUMEN
There is a relationship between schistosomiasis and anemia, although the magnitude and exact mechanisms involved are unclear. In a cohort of 580 Schistosoma japonicum-infected 7- to 30-year-old patients from Leyte, The Philippines, we evaluated the impact of reinfection with S. japonicum after treatment with praziquantel on the mean hemoglobin level, iron-deficiency (IDA) and non-iron-deficiency anemia (NIDA), and inflammatory markers. All participants were treated at baseline and followed up every 3 months for a total of 18 months. At each follow-up, participants provided stools to quantify reinfection and venous blood samples for hemograms and measures of iron status and inflammation. After 18 months, reinfection with S. japonicum was associated with a lower mean hemoglobin level (-0.39 g/dl; 95% confidence interval [95% CI], -0.63 to -0.16) and 1.70 (95% CI, 1.10 to 2.61) times higher odds of all-cause anemia than those without reinfection. Reinfection was associated with IDA for high reinfection intensities only. Conversely, reinfection was associated with NIDA for all infection intensities. Reinfection was associated with serum interleukin-6 responses (P<0.01), and these responses were associated with NIDA (P=0.019) but not with IDA (P=0.29). Our results provide strong evidence for the causal relationship between S. japonicum infection and anemia. Rapidly reinfected individuals did not have the positive treatment effect on hemoglobin seen in nonreinfected individuals. The principle mechanism involved in S. japonicum-associated anemia is that of proinflammatory cytokine-mediated anemia, with iron deficiency playing a role in high-intensity infections. Based on the proposed mechanism, anemia is unlikely to be ameliorated by iron therapy alone.
Asunto(s)
Anemia/inmunología , Anemia/parasitología , Antihelmínticos/farmacología , Praziquantel/farmacología , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/tratamiento farmacológico , Esquistosomiasis Japónica/inmunología , Adolescente , Adulto , Anemia/patología , Anemia Ferropénica/inmunología , Anemia Ferropénica/parasitología , Anemia Ferropénica/patología , Animales , Antihelmínticos/administración & dosificación , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inflamación/inmunología , Inflamación/parasitología , Inflamación/patología , Masculino , Praziquantel/administración & dosificación , Recurrencia , Schistosoma japonicum/efectos de los fármacos , Esquistosomiasis Japónica/patologíaRESUMEN
Although schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses to Schistosoma japonicum soluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, where S. japonicum is endemic. S. japonicum transmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-gamma), IL-5/IFN-gamma, and IL-13/IFN-gamma, in response to SWAP predicted a 1.4- to 2.9-month longer time to reinfection (P < 0.05) and a 27 to 55% lower intensity of reinfection (P < 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6- to 2.2-month longer time to reinfection (P < 0.05) and a 30 to 41% lower intensity of reinfection (P < 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P = 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance to S. japonicum and support Sj97 as a leading vaccine candidate for this parasite.
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Citocinas/metabolismo , Schistosoma japonicum/inmunología , Esquistosomiasis Japónica/inmunología , Células Th2/inmunología , Células Th2/metabolismo , Adolescente , Adulto , Animales , Niño , Femenino , Humanos , Inmunidad Innata , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Esquistosomiasis Japónica/tratamiento farmacológico , Esquistosomiasis Japónica/epidemiología , Extractos de Tejidos , AguaRESUMEN
In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6, and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and C-reactive protein (CRP) were measured to examine the association between these markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the majority of cases were mild (grade I), and severe (grade II or grade III) cases occurred only in male individuals. Compared with individuals without HF, those with severe HF--and, to a lesser degree, those with mild HF--had a significantly lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a higher level of CRP and were more likely to produce IL-6; furthermore, those with severe HF had a significantly higher level of IL-1, compared with those either without HF or with mild HF. These findings suggest that even mild HF is associated with nutritional morbidity and underscore the importance of early recognition and treatment. In addition, our data are consistent with the hypothesis that, by systemically increasing the levels of the proinflammatory cytokines IL-1 and IL-6, HF causes undernutrition and anemia.