Kurt Z. Long

Association of diarrheagenic Escherichia coli pathotypes with infection and diarrhea among Mexican children and association of atypical enteropathogenic E. coli with acute diarrhea.

ABSTRACT Seventy-six children ≤2 years old were prospectively followed for 1 year in a peri-urban community of Mexico City to determine asymptomatic infection and acute diarrhea associated with diarrheagenic Escherichia coli pathotypes (DEPs). By use of a pathogen-specific multiplex PCR, DEPs were sought in 795 stool samples, of which 125 (16%) were positive for DEP; of these, 4 represented shedding episodes and 4 parasite coinfections. Most single-DEP infections (85/117) were asymptomatic (P < 0.001), and of the 32 DEP diarrhea episodes, 41% were associated with atypical enteropathogenic E. coli (aEPEC), 37.5% with enterotoxigenic E. coli, 9% with typical EPEC, 9% with enteroinvasive E. coli, and 3% with Shiga toxin-producing E. coli strains. Among the 76 children, 54 had at least one stool positive for DEP, of which 23 experienced a DEP-associated diarrhea episode. In the last group of children, DEP infection was significantly associated with a diarrhea episode (relative risk [RR] = 2.5; 95% confidence interval [CI], 1.79 to 3.57; P < 0.001), with ETEC (RR = 2.30; 95% CI, 1.49 to 3.54; P = 0.003) and aEPEC (RR = 1.92; 95% CI, 1.23 to 3.0; P = 0.019) being the pathotypes associated with diarrhea. aEPEC-associated diarrhea episodes were frequently in the <12-month age group (RR = 2.57; 95% CI, 1.05 to 6.27; P = 0.04). aEPEC infections were distributed all year round, but associated diarrheal episodes were identified from April to October, with a May-June peak (rainy season). Most ETEC infections and diarrhea episodes characteristically occurred during the summer (rainy season), with a diarrhea peak in August. Of all DEPs, only aEPEC was associated with acute diarrhea episodes lasting 7 to 12 days (P = 0.019). DEPs are important causes of community-acquired enteric infection and diarrhea in Mexican children.

Asymptomatic Norovirus Infection in Mexican Children

ABSTRACT Sixty-three children in periurban Mexico City were examined for the occurrence of asymptomatic norovirus (NoV) infection from June to August 1998. NoV was detected in 48 of 161 stool specimens (29.8%), with 31 children (49.2%) having at least one positive stool. Asymptomatic NoV infection occurred commonly during summertime in a Mexican pediatric population.

Associations between Mucosal Innate and Adaptive Immune Responses and Resolution of Diarrheal Pathogen Infections

ABSTRACT The identification of immune response mechanisms that contribute to the control of diarrheal disease in developing countries remains an important priority. We addressed the role of fecal chemokines and cytokines in the resolution of diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from 127 Mexican children 5 to 15 months of age enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL-8, IL-10, and interferon-γ (IFN-γ) were determined. Hazard models incorporating cytokine variables were fit to durations of asymptomatic and symptomatic pathogen infections, controlling for treatment group. Increased levels of TNF-α and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-γ levels were associated with decreased and increased durations, respectively, of both EPEC and ETEC infections. Increased IL-10 levels were associated with increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of both asymptomatic and symptomatic ETEC infections. Increased levels of MCP-1, IFN-γ, IL-4, and IL-5 were associated with increased G. lamblia infection duration, while increased IL-8 levels were associated with decreased durations. Differences in proinflammatory and Treg cytokine levels are associated with differences in the resolution of inflammatory and noninflammatory pathogen infections.

Impact of Vitamin A on Selected Gastrointestinal Pathogen Infections and Associated Diarrheal Episodes among Children in Mexico City, Mexico

BACKGROUND The overall effect of vitamin A supplementation on diarrheal disease in community trials may result from its effect on specific diarrheal pathogens. METHODS We conducted a placebo-controlled, double-blind trial of the prophylactic effect of vitamin A on gastrointestinal pathogen infections and clinical symptoms among 188 children in Mexico City, Mexico, from January 1998 to May 1999. Children 6-15 months of age were randomly assigned to receive either a vitamin A supplement (for children <12 months of age, 20,000 international units [IU] of retinol; for children > or =12 months of age, 45,000 IU of retinol) every 2 months or a placebo and were followed for up to 15 months. Stool samples, collected semimonthly, were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EIEC), and Giardia lamblia. RESULTS Vitamin A supplementation reduced the prevalence of EPEC infections (rate ratio [RR], 0.52 [95% confidence interval {CI}, 0.23-0.86]) and led to shorter durations of both EPEC and ETEC infections. Supplementation also reduced the prevalence of EPEC-associated diarrhea (RR, 0.41 [95% CI, 0.16-1.00]), EPEC-associated fever (RR, 0.15 [95% CI, 0.02-0.98]), and G. lamblia-associated fever (RR, 0.27 [95% CI, 0.13-0.80]). Finally, children who received vitamin A supplementation had shorter durations of EPEC-associated diarrhea than did children who did not receive supplementation but had longer durations of G. lamblia-associated diarrhea. CONCLUSIONS These results suggest that the effect of vitamin A supplementation on clinical outcomes may be pathogen dependent.

Effect of Vitamin A and Zinc Supplementation on Gastrointestinal Parasitic Infections Among Mexican Children

OBJECTIVE. Gastrointestinal parasites continue to be an important cause of morbidity and stunting among children in developing countries. We evaluated the effect of vitamin A and zinc supplementation on infections by Giardia lamblia, Ascaris lumbricoides, and Entamoeba histolytica. METHODS. A randomized, double-blind, placebo-controlled trial was conducted among 707 children who were 6 to 15 months of age and from periurban areas of Mexico City, Mexico, between January 2000 and May 2002. Children, who were assigned to receive either vitamin A every 2 months, a daily zinc supplement, a combined vitamin A and zinc supplement, or a placebo, were followed for 1 year. The primary end points were the 12-month rates and durations of infection for the 3 parasites and rates of parasite-associated diarrheal disease as determined in stools collected once a month and after diarrheal episodes. RESULTS. G lamblia infections were reduced and A lumbricoides infections increased among children in the combined vitamin A and zinc group or the zinc alone group, respectively. Durations of Giardia infections were reduced among children in all 3 treatment arms, whereas Ascaris infections were reduced in the vitamin A and zinc group. In contrast, E histolytica infection durations were longer among zinc-supplemented children. Finally, E histolytica–and A lumbricoides–associated diarrheal episodes were reduced among children who received zinc alone or a combined vitamin A and zinc supplement, respectively. CONCLUSIONS. We found that vitamin A and zinc supplementation was associated with distinct parasite-specific health outcomes. Vitamin A plus zinc reduces G lamblia incidence, whereas zinc supplementation increases A lumbricoides incidence but decreases E histolytica–associated diarrhea.

Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study

BackgroundThe prevalence of obesity among Mexican women is high and it could be related to micronutrient status. We evaluated in a cross-sectional study the associations of zinc and vitamins A, C and E concentrations with BMI, central adiposity, body fat and leptin concentration.MethodsWomen aged 37 ± 7.5 years (n = 580) from 6 rural communities in Mexico were evaluated. Anthropometric measurements included weight, height, waist and hip circumference. A fasting blood sample was taken for the analysis of glucose, lipid profile, leptin, zinc, and vitamins A, C and E. Body composition was determined by DEXA (Hologic Mod Explorer).ResultsThe prevalence of overweight and obesity was 36% (BMI > 25 Kg/m2) and 44% (BMI > 30 Kg/m2), respectively. Prevalence of zinc and vitamins C and E deficiencies were similar in obese, overweight and normal weight women. No vitamin A deficiency was found. Vitamin C was negatively associated with BMI, waist-to-height ratio, and leptin concentrations (p < 0.05). Vitamin A was positively associated with leptin (p < 0.05). When stratifying by BMI, % body fat and waist circumference, high leptin concentrations were associated with lower zinc and lower vitamin C concentrations in women with obesity (p < 0.05) and higher vitamin A concentrations in women without obesity (p < 0.01). Vitamin E status was not associated with any markers of obesity.ConclusionZinc and vitamins A and C are associated with obesity, adiposity and leptin concentration in women from rural Mexico, and may play an important role in fat deposition. The causality of these associations needs to be confirmed.

Vitamin A Supplementation Has Divergent Effects on Norovirus Infections and Clinical Symptoms among Mexican Children

BACKGROUND The effect of vitamin A supplementation on viral gastrointestinal infections among young children living in developing countries remains unclear. METHODS The effect of vitamin A supplementation on norovirus (NoV) infection among 127 Mexican children 5-15 months of age was studied in a randomized, placebo-controlled trial during June-August 1998. Stool samples collected every 2 weeks and after diarrheal episodes were screened for NoV and characterized at the genogroup level (GI and GII). RESULTS Of the stool samples collected, 29.9% were positive for NoV, and NoV GI and NoV GII were found in 55.4% and 46.4% of the positive samples, respectively. Vitamin A supplementation reduced the prevalence of NoV GII infections (rate ratio [RR], 0.60 [95% confidence interval {CI}, 0.20-0.82]), increased the length of both NoV GI and GII shedding, and decreased the prevalence of NoV-associated diarrhea (RR, 0.51 [95% CI, 0.26-0.97]). CONCLUSIONS These findings suggest that NoV is an important cause of pediatric diarrhea in this study population and that vitamin A supplementation has divergent effects on specific outcomes of NoV infection.

Low Serum Concentrations of Carotenoids and Vitamin E Are Associated with High Adiposity in Mexican-American Children

Mexican-American children have a high prevalence of overweight/obesity. Micronutrient deficiencies may be contributing to the development of greater adiposity in these children. This study investigated the relations between adiposity and serum concentrations of carotenoids, retinol, and vitamin E among Mexican-American children 8-15 y of age included in the 2001-2004 U.S. NHANES. Associations of the outcomes of childrens body mass index (BMI), truncal fat mass (TrFM), and total body fat mass (TBFM) with serum concentrations of α-carotene, cis-β-carotene, trans-β-carotene, retinol, and α-tocopherol were determined by using linear, quantile, and multinomial regression models. BMI was inversely associated with serum concentrations of α-carotene (β = -0.88, P < 0.05), trans-β-carotene (β = -2.21, P < 0.01), cis-β-carotene (β = -2.10, P < 0.01), and α-tocopherol adjusted for total cholesterol ratio (β = -3.66, P < 0.01), respectively. Similar inverse associations were found with TrFM and TBFM. Higher cis-β-carotene and α-tocopherol serum concentrations were associated with reduced probability of overweight (OR: 0.57; 95% CI: 0.37, 0.89; P < 0.05; and OR: 0.56; 95% CI: 0.37, 0.86; P < 0.05; respectively) and obesity (OR: 0.39; 95% CI: 0.26, 0.58; P < 0.01; and OR: 0.38; 95% CI: 0.24, 0.60; P < 0.01; respectively). Higher retinol serum concentrations were associated with increased probability of overweight and obesity (OR: 2.01; 95% CI: 1.26, 3.22; P < 0.01; and OR: 2.90; 95% CI: 1.65, 5.09; P < 0.01; respectively). Significant inverse associations were found between serum concentrations of carotenoids and vitamin E and adiposity among Mexican-American children, but serum retinol concentrations were positively associated with adiposity. Future research is needed to understand the causes and consequences of micronutrient status on adiposity and comorbidities.

Supplementation with vitamin A reduces watery diarrhoea and respiratory infections in Mexican children

Previous clinical vitamin A trials have found no consistent effect on diarrhoeal disease and respiratory tract infection. These inconsistent results may be due to the distinct effects vitamin A supplementation has among children stratified by factors related to socio-economic status, nutritional status and season. We evaluated the effect of supplementation on the overall incidence of diarrhoeal disease and respiratory tract infections and on the incidence among children stratified by these factors. A total of 188 children, aged 6-15 months, from periurban, marginalized communities of Mexico City were assigned to receive vitamin A ( < 12 months of age, 20,000 IU retinol; >or= 12 months, 45,000 IU retinol) or a placebo every 2 months, and were followed for up to 15 months. Project personnel visited households twice a week to determine the onset and duration of diarrhoeal disease and respiratory tract infections. Vitamin A supplementation had no significant effect on risk of overall diarrhoeal disease but reduced mild watery diarrhoea (incidence rate ratio (RR) 0.69; 95 % CI 0.50, 0.93) and cough with fever (RR 0.69; 95 % CI 0.48, 0.98). Vitamin A supplementation decreased diarrhoeal disease during the summer (RR 0.74; 95 % CI 0.57, 0.94), among non-stunted children (RR 0.69; 95 % CI 0.52, 0.93) and among children from households with better socio-economic measures. Heterogeneity in the response to vitamin A supplementation may reflect heterogeneity in the aetiology and epidemiology of diarrhoeal disease and respiratory tract infections and the impact that supplementation has on the immune response.

Vitamin A supplementation modifies the association between mucosal innate and adaptive immune responses and resolution of enteric pathogen infections

BACKGROUND The efficacy of vitamin A supplementation on diarrheal disease morbidity may reflect the divergent effects that supplementation has on pathogen-specific immune responses and pathogen-specific outcomes. OBJECTIVE We examined how vitamin A supplementation modified associations between gut-cytokine immune responses and the resolution of different diarrheal pathogen infections. DESIGN Stools collected from 127 Mexican children who were 5-15 mo old and enrolled in a randomized, placebo-controlled vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of interleukin (IL)-6, IL-8, IL-4, IL-5, IL-10, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by using an enzyme-linked immunosorbent assay. Hazard models that incorporated categorized cytokine variables (ie, nondetectable, less than the median of detectable concentrations, and at least the median of detectable concentrations) were fit to the length of pathogen infections stratified by treatment group. RESULTS Vitamin A-supplemented children with fecal MCP-1 or IL-8 concentrations less than the median of detectable concentrations and IL-10 concentrations of at least median concentrations had longer durations of EPEC infection than did children in the placebo group. In supplemented children, detectable fecal TNF-α or IL-6 concentrations were associated with shorter ETEC infection durations, whereas MCP-1 concentrations of at least the median were associated with longer infection durations. Children in this group who had IL-4, IL-5, or IFN-γ concentrations of at least median detectable concentrations had shorter durations of G. lamblia infection. CONCLUSION The effect of supplementation on associations between fecal cytokine concentrations and pathogen infection resolution depends on the role of inflammatory immune responses in resolving specific pathogen infections.