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Remigio M Olveda

Publications and source records attributed to Remigio M Olveda.

17 recordsLinked to original sources
PubMed2007

Statistical evidence for GLM regression parameters: a robust likelihood approach.

When a likelihood ratio is used to measure the strength of evidence for one hypothesis over another, its reliability (i.e. how often it produces misleading evidence) depends on the specification of the working model. When the working model happens to be the 'true' or 'correct' model, the probability of observing strong misleading evidence is low and controllable. But this is not necessarily the case when the working model is misspecified. Royall and Tsou (J. R. Stat. Soc., Ser. B 2003; 65:391-404) show how to adjust working models to make them robust to misspecification. Likelihood ratios derived from their 'robust adjusted likelihood' are just as reliable (asymptotically) as if the working model were correctly specified in the first place. In this paper, we apply and extend these ideas to the generalized linear model (GLM) regression setting. We provide several illustrations (both from simulated data and real data concerning rates of parasitic infection in Philippine adolescents), show how the required adjustment factor can be obtained from standard statistical software, and draw some connections between this approach and the 'sandwich estimator' for robust standard errors of regression parameters. This substantially broadens the availability and the viability of likelihood methods for measuring statistical evidence in regression settings.

Adolescent↗
PubMed2006

Schistosoma japonicum reinfection after praziquantel treatment causes anemia associated with inflammation.

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.

Adolescent↗
PubMed2006

Pubertal development predicts resistance to infection and reinfection with Schistosoma japonicum.

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.

Adolescent↗
PubMed2006

Schistosomiasis japonica, anemia, and iron status in children, adolescents, and young adults in Leyte, Philippines 1.

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.

Adolescent↗
PubMed2006

Nutritional status improves after treatment of schistosoma japonicum-infected children and adolescents.

Studies addressing the relation between chronic schistosomiasis japonica and nutritional status are limited. We conducted a longitudinal treatment-reinfection study in Leyte, the Philippines, among 477 Schistosoma japonicum-infected subjects aged 7-20 y, to evaluate changes in nutritional status after treatment with praziquantel. Stool, Tanner stage, anthropometric indices, and hemoglobin (Hb) were evaluated at baseline, 4 wk post-treatment, and every 3 mo for 18 mo. Height-for-age Z-score (HAZ) and BMI Z-score (BMIZ) were calculated. Change scores relative to baseline were created for all outcome measures. Multilevel repeated-measures analyses were used to adjust for socioeconomic status, sex, either pubertal status or age, and household-level clustering. Z-scores improved modestly but significantly over time. BMIZ in children wasted at baseline improved the most [0.41 (0.26-0.56) Z-score unit] and HAZ improved only in children stunted at baseline [0.17 (0.l2-0.21) Z-score unit]. Hb improvement peaked at 15 mo and occurred only in subjects that were anemic at baseline [peak improvement: 8.3 (6.0-10.6) g/L] and in males [peak improvement 4.7 (2.9-6.6) g/L]. Reinfection, evaluated as egg count over time and egg count 3 mo earlier to assess a delay in effect, was inversely associated with improvement in Hb (P = 0.06 and 0.004, respectively). High-intensity reinfection at 18 mo was associated with significantly less absolute growth from baseline compared with lower-intensity and no reinfection. Based on the peak Hb improvement at 15 mo post-treatment, annual treatment intervals are recommended to reduce schistosomiasis-associated nutritional morbidity.

Adolescent↗
PubMed2006

T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum.

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.

Adolescent↗
PubMed2006

Pro-inflammatory cytokines and C-reactive protein are associated with undernutrition in the context of Schistosoma japonicum infection.

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.

Adolescent↗
PubMed2005

Functional significance of low-intensity polyparasite helminth infections in anemia.

BACKGROUND: We wanted to quantify the impact that polyparasite infections, including multiple concurrent low-intensity infections, have on anemia. METHODS: Three stool samples were collected and read in duplicate by the Kato-Katz method in a cross-sectional sample of 507 children from Leyte, The Philippines. The number of eggs per gram of stool was used to define 3 infection intensity categories--uninfected, low, and moderate/high (M+)--for 3 geohelminth species and Schistosomiasis japonicum. Four polyparasite infection profiles were defined in addition to a reference profile that consisted of either no infections or low-intensity infection with only 1 parasite. Logistic regression models were used to quantify the effect that polyparasitism has on anemia (hemoglobin level <11 g/dL). RESULTS: The odds of having anemia in children with low-intensity polyparasite infections were nearly 5-fold higher (P = .052) than those in children with the reference profile. The odds of having anemia in children infected with 3 or 4 parasite species at M+ intensity were 8-fold greater than those in children with the reference profile (P < .001). CONCLUSION: Low-intensity polyparasite infections were associated with increased odds of having anemia. In most parts of the developing world, concurrent infection with multiple parasite species is more common than single-species infections. This study suggests that concurrent low-intensity infections with multiple parasite species result in clinically significant morbidity.

Adolescent↗
PubMed2005

Nutritional status and serum cytokine profiles in children, adolescents, and young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte, Philippines.

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.

Adolescent↗
PubMed2005

Schistosoma japonicum and occult blood loss in endemic villages in Leyte, the Philippines.

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.

Adolescent↗
PubMed2005

Relationship between Schistosoma japonicum and nutritional status among children and young adults in Leyte, the Philippines.

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.

Adolescent↗
PubMed2005

Helminth infection and cognitive impairment among Filipino children.

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.

Adolescent↗
PubMed2004

Antigen-specific antibody isotype patterns to schistosoma japonicum recombinant and native antigens in a defined population in Leyte, the Philippines.

We describe antibody isotype patterns resulting from Schistosoma japonicum infection among 155 individuals 5-76 years old from a community in Leyte, The Philippines. Their exposure, infection, and reinfection status had been observed in a previously described water contact study used to categorically classify them as putative resistant or susceptible individuals. Antigens tested for specific antibody isotype responses were soluble worm antigen preparation (SWAP) and soluble egg antigen (SEA) and a panel of recombinant molecules. The study was aimed primarily at evaluating antigen-specific antibody responses and their potential in inducing protection among putative resistant individuals. Specific antibody responses suggestive of an involvement in protection were an IgE response to SWAP among females less than 20 years of age (5-19) and IgA responses to SWAP in the younger (5-19 years) age groups. Compatible with other studies on human schistosomes, IgM reactivities to SWAP and SEA in the 5-19-year-old age group predicted susceptibility as did IgG4 responses to recombinant paramyosin.

Adolescent↗
PubMed2002

Difficulties and strategies in the control of schistosomiasis in the Philippines.

Schistosomiasis japonica continues to remain a public health problem in the Philippines affecting 10 out of 16 regions with 6.7 million people at risk mostly farmers and fisher folks. Early efforts focused on snail control in the absence of an effective drug against the disease. Discovery of praziquantel shifted control focus from the expensive snail control to a more manageable one involving case detection and treatment. At present, the government's objective is to reduce morbidity by chemotherapy and supplemented with environmental sanitation, health education, and mollusciciding. In the past, external funds infused into government control programs helped a lot in bringing down prevalence rates of the disease in many highly endemic areas. The end of this foreign assistance has expectedly affected implementation of the programs bringing fears of a possible resurgence in many endemic areas. Such anxiety is also founded on the perennial problems of low disease awareness among people at risk, aggravated security problem, poverty and the negative effects of a devolved set-up in the health care delivery system. Experts suggest that the national health department should be more aggressive in dealing with the disease in terms of ensuring implementation and of continuously searching for better and more improved methods of control. Any new strategy should always consider the devolved set up of the health department.

Anthelmintics↗
PubMed2002

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: I. Assessment of 'resistance' versus 'susceptibility' to S. japonicum infection.

This study describes the categorical classification of 155 individuals living in an endemic village in Macanip, Leyte, Philippines as 'resistant' or 'susceptible' to Schistosoma japonicum infection using available exposure, infection and reinfection data collected from a 3-year water contact (WC) study. Epidemiological parameters including age, sex, and infection intensities in relation to observed reinfection patterns are also described. This classification was used in subsequent immunological studies described in two accompanying papers to identify protective immune mechanisms among resistant individuals induced by defined candidate vaccine molecules for S. japonicum. The study suggests that individuals who were most vulnerable to rapid reinfection were children belonging to the 5-14 age group. A drop in incidence at age group 15-19 and decreased intensity of infection starting at this age group and older (15+) suggests development of immunity. Controlling for the effect of the other variables, a multivariate analysis showed significant association for sex, in that females were more likely to be resistant. This implies that other than acquired immunity to infection, some age-dependent host factors may also play an important role in the overall changes of reinfection patterns seen in schistosomiasis japonica in this population.

Adolescent↗
PubMed2002

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: II. Cellular immune responses to S. japonicum recombinant and native antigens.

Cellular immune responses to specific Schistosoma japonicum recombinant and native antigens were investigated in a defined study population of 155 individuals in the Philippines, where data collected from a 3-year observation of exposure, infection and reinfection pattern were used to categorically classify putative 'resistant' and 'susceptible' individuals. Using peripheral blood mononuclear cells (PBMC) of individuals enrolled in the study, in vitro lymphocyte proliferation and cytokine (IFN-gamma, IL-5 and IL-10) production in response to defined recombinant antigens (97 kDa paramyosin, 22 kDa tegumental antigen, 37 kDa glyceraldehyde-3-phosphate dehydrogenase, 14 kDa fatty acid binding protein and 28 kDa gluthathione-S-tranferase) and native antigen soluble worm antigen preparation (SWAP) were measured. Cellular responses to the recombinant and SWAP antigens suggest that Th1 type of response appear to be important in predicting resistance in this population. Of the five recombinant antigens tested, rPMY induced significant levels of IFN-gamma. The production of IL-10, a Th2-type cytokine was strongly implicated in immune regulation. Of importance was the evidence found for SWAP and rPMY induced IFN-gamma responses in predicting 'resistance'. It was noted that these associations were significant even after the effect of age and sex were accounted for in a multivariate analysis.

Adolescent↗