The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases

OBJECTIVE: The demographic, clinical, and epidemiological features of subclinical/silent celiac disease in Italy were analyzed in a multicenter study carried out with the participation of 42 centers, in the years between 1990 and 1994. METHODS: One thousand twenty-six subclinical/silent patients (644 children and 382 adults, 702 women and 324 men) were considered eligible for the study. RESULTS: The prevalence of the subclinical/silent form increased significantly during the study both in adults (p < 0.001) and in children (p < 0.005), but its prevalence was always lower (p < 0.001) in children than in adults. This increase appears more likely due to a greater diagnostic awareness and to a better use of screening than to a higher number of subclinical/silent cases. Whereas in 1990 a significantly higher proportion (p < 0.001) of subclinical/silent celiac patients was diagnosed in Northern Italy rather than in Southern-Insular Italy, both in adults (46.7% vs 17.2%) and in children (22.0% vs 9.0%), in 1994 such a difference was no longer conspicuous. Both in children and in adults, iron-deficiency anemia appeared to be the most frequent extraintestinal symptom, followed by short stature in children and cutaneous lesions of dermatitis herpetiformis in adults. In 25.9% of the cases another disease was present, with a significantly higher frequency (p < 0.05) in adults (30.1%) than in children (20.7%). Diabetes and atopy appeared to be the most frequently associated conditions both in children and in adults. CONCLUSIONS: This study has provided an analysis of the largest series of subclinical/silent celiac disease reported to date. In Italy, this form is most frequently recognized in adults, and prospective studies will clarify whether the lower frequency observed in children is a real or apparent phenomenon.     

Nitric oxide, malaria, and anemia: inverse relationship between nitric oxide production and hemoglobin concentration in asymptomatic, malaria-exposed children.

The cause of the anemia associated with chronic, intermittent, asymptomatic, low-level parasitemia in children in malaria-endemic endemic areas is not well understood. Nitric oxide (NO) decreases erythropoiesis, and it is likely an important mediator of anemia of chronic disease. Production of NO is decreased in acute uncomplicated and cerebral malaria, but it is increased in asymptomatic Tanzanian children (with or without parasitemia). We hypothesized that chronic overproduction of NO in these asymptomatic children contributes to the anemia associated with subclinical/subpatent malaria. In 44 fasting, asymptomatic, malaria-exposed, Tanzanian children, NO production (measured using fasting urine NOx excretion) was inversely associated with hemoglobin concentration (P = 0.03, controlling for age and gender). Using multiple linear regression, hemoglobin concentration was negatively associated with parasitemia (P = 0.005). After controlling for age and parasitemia, NO was no longer an independent predictor of anemia. One of the mechanisms of parasite-related anemia in such children may be through the adverse hematologic effects of parasite-induced NO production.     

Fascioliasis in relatives of patients with Fasciola hepatica infection in Peru

High prevalence rates of human fascioliasis have been described in several regions of Peru. We surveyed 20 families in an endemic area of Peru in order to determine the proportion of infection with F. hepatica in relatives of diagnosed subjects and in order to identify associated risk factors. The study included feces and blood samples of 93 subjects. Ages ranged from one to 53 (mean = 18.6; SD = 14.2). The overall prevalence of fascioliasis by fecal examinations was 33.3% (n = 83) and by serology, 51.9% (n = 86). The prevalence in age group I (< or = 19 years old) by coprological and serological tests was 61.4% and 75.9%, respectively; in group II (> 19 years old) 15.4% and 37.5%. The main associated risk factor with fascioliasis was eating salads (OR = 3.29, CI = 1.2 - 9.0, p = 0.02). In conclusion, human fascioliasis is highly prevalent in the relatives of index cases and the most significant risk factor of acquiring fascioliasis in the family is eating salads in endemic areas.     

Hyperendemic fascioliasis associated with schistosomiasis in villages in the Nile Delta of Egypt

Coprologic surveys were carried out in villages of the Behera Governorate in the Nile Delta region of Egypt to characterize the epidemiologic features of human fascioliasis caused by Fasciola hepatica and F. gigantica in this lowland endemic area by comparison with fascioliasis caused by only F. hepatica in areas hyperendemic for human disease in the Andean highlands of South America. The fascioliasis prevalences detected (range = 5.2-19.0%, mean = 12.8%) are the highest obtained in Egypt. The comparison with previous results suggests that in the Nile Delta, fascioliasis is spreading from an original situation of sporadic human cases in well-known endemic foci for animal disease to an endemic distribution in humans, which may be characterized as a mesoendemic region that includes several hyperendemic areas for human disease. As in Andean countries, a relationship with sex was found, although in Egypt prevalences, but not intensities, appeared to be significantly higher in females. All ages appear to be susceptible to liver fluke infection, with prevalences and intensities being lower before and after school age, a situation that is consistent with that detected in Andean countries, although the peak in the 9-11-year-old age group appears less pronounced in Egypt. The intensities were very high when compared with those found in subjects sporadically infected in areas endemic for animal disease, but relatively low for a hyperendemic situation, although the intensities may not be conclusive because of the transmission seasonality of fascioliasis in the Nile Delta. The marked similarities in the qualitative and quantitative spectrums of protozoans and helminths, multiparasitisms, and associations between liver flukes and other parasitic species suggest physiographic-hydrographic and behavioral-social characteristics similar in all areas hyperendemic for human fascioliasis, which are independent of other factors such as climate, altitude, and cultural or religious features. The significant positive association between liver fluke infection and schistosomiasis mansoni detected in one locality has never been described elsewhere, and must be considered relevant from clinical, pathologic, diagnostic, and therapeutic points of view. Interestingly, the relationships of schistosomiasis prevalences and intensities with sex and age follow patterns similar to those found in fascioliasis.     

Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism

We investigated possible associations between subclinical hypothyroidism and atherosclerotic diseases (ischemic heart disease and cerebrovascular disease) and mortality. Of 2856 participants (mean age 58.5 yr) in a thyroid disease screening between 1984 and 1987, 257 subjects with subclinical hypothyroidism (TSH > 5.0 mU/liter) and 2293 control subjects (TSH range 0.6-5.0 mU/liter) were analyzed. In the baseline cross-sectional analysis, subclinical hypothyroidism was associated with ischemic heart disease independent of age, systolic blood pressure, body mass index, cholesterol, smoking, erythrocyte sedimentation rate, or presence of diabetes mellitus [odds ratio (OR), 2.5; 95% confidence interval (95% CI), 1.1-5.4 in total subjects and OR, 4.0; 95% CI, 1.4-11.5 in men] but not in women. However, there was no association with cerebrovascular disease (OR, 0.9; 95% CI, 0.4-2.4). We were unable to detect an influence of thyroid antibody presence on the association between subclinical hypothyroidism and ischemic heart disease. In a 10-yr follow-up study until 1998, increased mortalities from all causes in yr 3-6 after baseline measurement were apparent in men with subclinical hypothyroidism (hazard ratio, 1.9-2.1) but not in women, although specific causes of death were not determined. Our results indicate that subclinical hypothyroidism is associated with ischemic heart disease and might affect all-cause mortality in men.     

Increased anti-Echinococcus granulosus antibody positivity in Fasciola hepatica infection

Background/aims: Parasitic helminths express some antigen, which often accounts for serological cross-reactions. The aim of this study was to determine the prevalence of antiEchinococcus granulosus antibody in patients with Fasciola hepatica infection using indirect immunofluorescence assay. Materials and Methods: The study population consisted of the following groups: Fasciola hepatica group (n=22), hydatid disease group (n=22) and healthy control group (n=24). Indirect immunofluorescence assay for Echinococcus granulosus was performed in all groups. Results: Indirect immunofluorescence assay was positive in all patients with hydatid disease, in 13 of 22 (59%) patients with fascioliasis and in 2 of 24 (8%) healthy subjects. The positivity rate of indirect immunofluorescence assay was significantly higher in the hydatid disease group compared to the fascioliasis group (p<0.001) and compared to the control group (p<0.001), and it was significantly higher in the fascioliasis group compared to the control group (p=0.001). Antibody titer was 1/100 in 7 patients, 1/320 in 12 patients and 1/1000 in 3 patients with hydatid disease. Indirect immunofluorescence assay was positive in 10 of 15 patients with hepatic phase and in 3 of 7 patients with biliary phase of fascioliasis. The antibody titer was 1/100 in 6 and 1/320 in 7 patients with fascioliasis. The antibody titer was 1/100 in both healthy subjects. Conclusions: Indirect immunofluorescence assay for Echinococcus granulosus may be positive in a majority of patients with Fasciola hepatica infection and in some healthy subjects.     

Functional capacity in children and young adults with sickle cell disease undergoing evaluation for cardiopulmonary disease

Although cardiopulmonary disease is associated with decreased functional capacity among adults with sickle cell disease (SCD), its impact on functional capacity in children with SCD is unknown. We evaluated 6‐min walk (6MW) distance in 77 children and young adults with SCD undergoing screening for cardiopulmonary disease. Of 30 subjects who also underwent cardiopulmonary exercise testing, we found evidence for decreased exercise capacity in a significant proportion. Exercise capacity was related to baseline degree of anemia and was significantly lower in subjects with a history of recurrent acute chest syndrome. We found that 6MW distance adjusted for weight and body surface area was shorter in subjects with restrictive lung disease but that only 6MW adjusted for weight remained significantly shorter when we controlled for baseline hemoglobin. Exercise capacity was not significantly different in subjects with and without cardiopulmonary disease. We conclude that restrictive lung disease is associated with shorter 6MW distances in children and young adults with SCD, but that variables associated with decreased exercise capacity, other than anemia, remain unclear. Our study underscores the importance of further delineating the direct pathophysiologic processes that contribute to decreased exercise capacity observed among individuals with SCD and cardiopulmonary disease. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

The High Burden of Malaria in Primary School Children in Southern Malawi

Malaria among school children has received increased attention recently, yet there remain few detailed data on the health and educational burden of malaria, especially in southern Africa. This paper reports a survey among school children in 50 schools in Zomba District, Malawi. Children were assessed for Plasmodium infection, anemia, and nutritional status and took a battery of age-appropriate tests of attention, literacy, and numeracy. Overall, 60.0% of children were infected with Plasmodium falciparum, 32.4% were anemic and 32.4% reported sleeping under a mosquito net the previous night. Patterns of P. falciparum infection and anemia varied markedly by school. In multivariable analysis, higher odds of P. falciparum infection were associated with younger age and being stunted, whereas lower odds were associated with reported net use, higher parental education, and socioeconomic status. The odds of anemia were significantly associated with P. falciparum infection, with a dose–response relationship between density of infection and odds of anemia. No clear relationship was observed between health status and cognitive and educational outcomes. The high burden of malaria highlights the need to tackle malaria among school children.     

Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease

The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia.     

Anemia and malaria at different altitudes in the western highlands of Kenya

Malaria associated severe anemia in children is the most important complication of Plasmodium falciparum infection in sub-Saharan Africa. To evaluate anemia and malaria in an area with recurrent malaria epidemics in the western highlands of Kenya, we conducted cross-sectional surveys in four "lowland" (1440-1660 m) and two "highland" (1960 and 2040 m) villages in 2002. Among 1314 subjects randomly selected from all age groups, the overall prevalence of anemia (hemoglobin, Hb < 11 g/dl) was 14% and P. falciparum infection 17%. In children < or =5 years, anemia prevalence ranged from 57% at 1440 m to 11% at 2040 m and correlated with altitude (r = -0.88, P < 0.05). Similarly, P. falciparum prevalence ranged from 31 to 0% and correlated with altitude (r = -0.93, P < 0.01). Malnutrition defined by a body mass index <15th percentile characterized 39% of the population and the hookworm prevalence was 3.9%. In the lowland villages, anemia was most common in children < or =5 years of age (34%) followed by women of childbearing age (16%). A similar pattern was also observed in the highland villages. In these vulnerable populations, hemoglobin concentration was significantly associated with malaria infection, but not with malnutrition or hookworm infestation and comparisons of anemia prevalence between highland and lowland villages revealed that two-thirds of anemia could be attributed to malaria infection. The prevalence of severe anemia (Hb < 8 g/dl) was 1.5%; of these, 90% resided in lowland villages, 70% were under-fives, while 20% were women of childbearing age. In severely anemic subjects, the Hb concentration decreased further with malnutrition (P < 0.05). Anemia was more prevalent in the lowland villages characterized by high prevalence of P. falciparum infection. We conclude that malaria may also be the main cause of anemia in the highland fringe areas of sub-Saharan Africa. Measures that reduce the prevalence of malaria will consequently reduce anemia in both, young children and adult women and the need for blood transfusions associated with the risk of HIV-transmission.     

The metabolic syndrome and subclinical carotid atherosclerosis: the Northern Manhattan Study

The metabolic syndrome (MetS) is a distinctive phenotype associated with an increased risk of vascular disease. Carotid plaque is a surrogate marker of subclinical atherosclerosis and a powerful predictor of vascular outcomes. The relationship between the MetS and subclinical atherosclerosis in multiethnic populations has not been well characterized. The authors have evaluated the association of the MetS with subclinical atherosclerosis among 1895 community residents from the Northern Manhattan Study (mean age, 68.0+/-9.7 years; 59% women; 25% black; 22% white; 51% Hispanic). The prevalence of the MetS was 41% (35% in men, 45% in women), and 57% of subjects had carotid plaque. In a multivariate-adjusted logistic regression model, the MetS was a significant predictor of plaque presence (odds ratio, 1.36; 95% confidence interval, 1.10-1.67). Additionally, the number of MetS components was significantly associated with plaque prevalence. Further studies are needed to understand the role of the MetS in the progression from subclinical to clinical atherosclerotic disease.     

Central pulse wave velocity is responsible for increased brachial-ankle pulse wave velocity in subclinical hypothyroidism

Objective Subclinical hypothyroidism affects 5–15% of the general population, and is associated with increased morbidity from cardiovascular disease. We recently reported a significant increase in brachial‐ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor for the presence of cardiovascular disease, in subclinical hypothyroidism. The current study was performed to assess which arterial segment is responsible for enhanced baPWV in subclinical hypothyroidism. Patients and methods Central PWV (PWV in heart‐femoral segments), peripheral PWV (PWV in femoral‐ankle segments), and baPWV were measured in subclinical hypothyroid patients and normal subjects. Results Central PWV, baPWV, and peripheral PWV were significantly higher in subclinical hypothyroid patients than in normal subjects. BaPWV was significantly and positively correlated with central and peripheral PWV in both groups. However, a significant and positive correlation between central and peripheral PWV in normal subjects was not found in subclinical hypothyroid patients. Moreover, stepwise regression analysis showed that the association of central PWV with baPWV was stronger than that of peripheral PWV, whereas in normal subjects central PWV was not associated with baPWV. Conclusions Our results demonstrate that central and peripheral PWV are significantly higher in subclinical hypothyroid patients, and that the increase in baPWV depends more strongly on central PWV than on peripheral PWV in these patients. This suggests that increased elastic arterial stiffening of the aorta, rather than of peripheral muscular arteries, might be more responsible for increased general arterial stiffening in subclinical hypothyroid patients.     

Global patterns of child health: the role of nutrition

Almost two-thirds of the deaths of children around the world are directly or indirectly associated with nutritional deficiencies. Both protein-energy malnutrition and micronutrient deficiencies increase the risk of death from common diseases such as acute gastroenteritis, pneumonia and measles. Iron deficiency anemia is estimated to affect almost 25% of the world's population (equivalent to 3.5 billion people) resulting in high economic costs by adding to the burden on healthcare services, affecting learning in school and reducing adult productivity. Dietary practices frequently seen in older children and adolescents from industrialized countries, leading to frequent consumption of often nutrient-poor foods, may also put them at risk of micronutrient deficiencies. Marginal nutrient deficiencies in the developed world are increasingly accepted as risk factors for the development of chronic disease such as cardiovascular disease or some cancers.     

Fasciola hepatica: A cause of Obstructive Jaundice in an Elderly Man From Iran

Fascioliasis is a zoonotic infection caused by Fasciola hepatica. Humans can become accidental hosts of this parasite by ingesting contaminated drinking water or plants in endemic area. The north of Iran is one of the regions. This disease is rarely seen with jaundice caused by obstruction of the biliary tree. We report a case of human fascioliasis with obstructive jaundice who was diagnosed using endoscopic retrograde cholangiopancreatography (ERCP). This report confirms the diagnostic role of ERCP in patients with obstructive jaundice caused by biliary fascioliasis.     

Relation of Framingham risk score to subclinical atherosclerosis evaluated across three arterial sites

The Framingham risk score (FRS) is widely used in clinical practice to identify subjects at high risk for developing coronary heart disease. However, FRS may not accurately identify subjects at risk. We measured subclinical atherosclerosis in the coronary arteries and aorta with the presence of calcium and in the common carotid artery by intima-media thickness in 498 healthy subjects. The distribution of these subclinical atherosclerosis measures was evaluated across 3 strata of the FRS. Coronary arteries with the presence of calcium, aorta with the presence of calcium, and carotid artery by intima-media thickness were significantly independently associated with FRS. The FRS increased with the number of arterial sites with atherosclerosis; 69% of the subjects categorized in the low risk group (FRS <10%), 95% of the intermediate risk group (FRS 10% to 20%), and 100% of the high risk group (FRS >20%) had > or = 1 vascular imaging studies demonstrating subclinical atherosclerosis. In the low risk group, subjects with atherosclerosis had a longer history of lifetime smoking compared with those without atherosclerosis. In conclusion, subclinical atherosclerosis is prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis in different arterial sites in addition to FRS may be useful in targeting subjects for lifestyle and other interventions.     

Burden of Dengue Infection and Disease in a Pediatric Cohort in Urban Sri Lanka

Dengue is the most significant arthropod-borne viral infection of humans. Persons infected with dengue viruses (DENV) have subclinical or clinically apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock syndrome. Although recent studies estimated that the Indian subcontinent has the greatest burden of DENV infection and disease worldwide, we do not have reliable, population-based estimates of the incidence of infection and disease in this region. The goal of this study was to follow-up a cohort of 800 children living in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of the incidence of DENV infection and disease. Annual blood samples were obtained from all children to estimate dengue seroprevalence at enrollment and to identify children exposed to new DENV infections during the study year. Blood was also obtained from any child in whom fever developed over the course of the study year to identify clinically apparent DENV infections. At enrollment, dengue seroprevalence was 53.07%, which indicated high transmission in this population. Over the study year, the incidence of DENV infection and disease were 8.39 (95% confidence interval = 6.56–10.53) and 3.38 (95% confidence interval = 2.24–4.88), respectively, per 100 children per year. The ratio of clinically inapparent to apparent infections was 1.48. These results will be useful for obtaining more accurate estimates of the burden of dengue in the region and for making decisions about testing and introduction of vaccines.     

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years

OBJECTIVE: Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease. DESIGN: Cross-sectional study of a general population. PATIENTS: Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included. MEASUREMENTS: Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C-reactive protein and TSH. RESULTS: The main findings were a high incidence of subclinical hypothyroidism (19.7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C-reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3.4 (95% confidence interval 1.6-6.8) for developing cardiovascular disease compared to euthyroid age-matched males. CONCLUSION: Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low-grade inflammation (raised C-reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.     

Obesity—A Critical Issue in Preventive Cardiology: The Bogalusa Heart Study

Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/ insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention.     

Obesity--a critical issue in preventive cardiology: the Bogalusa Heart Study

Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention.