M. Lourdes Guerrero

Rotavirus Infection in Infants as Protection against Subsequent Infections

BACKGROUND Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. METHODS We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. RESULTS A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). CONCLUSION In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Efficacy of home-based peer counselling to promote exclusive breastfeeding: a randomised controlled trial.

BACKGROUND Exclusive breastfeeding is recommended worldwide but not commonly practised. We undertook a randomised controlled study of the efficacy of home-based peer counselling to increase the proportion of exclusive breastfeeding among mothers and infants residing in periurban Mexico City. METHODS Two intervention groups with different counselling frequencies, six visits (44) and three visits (52), were compared with a control group (34) that had no intervention. From March, 1995, to September, 1996, 170 pregnant women were identified by census and invited to participate in the study. Home visits were made during pregnancy and early post partum by peer counsellors recruited from the same community and trained by La Leche League. Data were collected by independent interview. Exclusive breastfeeding was defined by WHO criteria. FINDINGS 130 women participated in the study. Only 12 women refused participation. Study groups did not differ in baseline factors. At 3 months post partum, exclusive breastfeeding was practised by 67% of six-visit, 50% of three-visit, and 12% of control mothers (intervention groups vs controls, p<0.001; six-visit vs three-visit, p=0.02). Duration of breastfeeding was significantly (p=0.02) longer in intervention groups than in controls, and fewer intervention than control infants had an episode of diarrhoea (12% vs 26%, p=0.03). INTERPRETATION This is the first reported community-based randomised trial of breastfeeding promotion. Early and repeated contact with peer counsellors was associated with a significant increase in breastfeeding exclusivity and duration. The two-fold decrease in diarrhoea demonstrates the importance of breastfeeding promotion to infant health.

Serum Antibody as a Marker of Protection against Natural Rotavirus Infection and Disease

To determine whether naturally acquired serum IgA and IgG antibodies were associated with protection against rotavirus infection and illness, a cohort of 200 Mexican infants was monitored weekly for rotavirus excretion and diarrhea from birth to age 2 years. Serum samples collected during the first week after birth and every 4 months were tested for anti-rotavirus IgA and IgG. Children with an IgA titer >1:800 had a lower risk of rotavirus infection (adjusted relative risk [aRR], 0.21; P<.001) and diarrhea (aRR, 0. 16; P=.01) and were protected completely against moderate-to-severe diarrhea. However, children with an IgG titer >1:6400 were protected against rotavirus infection (aRR, 0.51; P<.001) but not against rotavirus diarrhea. Protective antibody titers were achieved after 2 consecutive symptomatic or asymptomatic rotavirus infections. These findings indicate that serum anti-rotavirus antibody, especially IgA, was a marker of protection against rotavirus infection and moderate-to-severe diarrhea.

Prevalence and genetic diversity of human caliciviruses (HuCVs) in Mexican children.

Human caliciviruses (HuCVs) contain two genera: “Norwalk‐like viruses” (NLVs) and “Sapporo‐like viruses” (SLVs). The importance of the two genera as a cause of acute gastroenteritis of infants and children remains unknown. Beginning in 1989, a birth cohort of children in Mexico was enrolled and monitored for acute gastroenteritis. A subset of 115 diarrhea stool specimens from 76 children and 66 non‐diarrhea stool specimens from 64 children was examined for HuCVs by RT‐PCR by using a primer pair (p289/290) that detects both NLVs and SLVs. Twenty‐two (19%) of the 115 diarrhea stool specimens and 5 (7%) of 66 non‐diarrhea stool specimens produced RT‐PCR products of expected size (319 bp for NLVs and 331 bp for SLVs). Twenty of the twenty‐seven strains were cloned and sequenced. Pairwise sequence analysis showed that 9 (60%) and 6 (40%) of the 15 strains from the diarrhea stools were NLVs and SLVs, respectively. The same proportions of NLVs (60%) and SLVs (40%) were observed in the non‐diarrhea stools. Strains in the NLV genus could be further divided into four clusters: Lordsdale, MxV, and HV and one potentially new cluster. Strains in the SLV genus could be divided into three clusters: Sapporo/82, Lon/92, and a potentially new cluster. Strains from the Lordsdale cluster were the most common among these children. The findings of both genera and multiple clusters of HuCVs co‐circulating and the identification of new strains of HuCVs in the population justify the need for future studies of HuCVs in infants and children. J. Med. Virol. 62:217–223, 2000.

Protection against infection with Giardia lamblia by breast-feeding in a cohort of Mexican infants

To determine whether breast-feeding protects infants against symptomatic and asymptomatic infection by Giardia lamblia, we followed 197 infants in a poor area of Mexico City from birth to 18 months of age; symptoms and feeding status were recorded weekly. Stool specimens were collected every 1 to 2 weeks and tested for Giardia by enzyme-linked immunosorbent assay. A mean of 1.0 Giardia infection per child-year was detected; 94 infants had a total of 139 infections; 17% of infections were symptomatic. Ninety-one percent of infants were breast fed from birth and 38% were breast fed at 1 year of age. Lack of breast-feeding was a significant risk factor for first Giardia infection at all ages. The adjusted incidence rate ratio for first Giardia infection for none versus complete breast-feeding was 5.0 (confidence interval (CI) 1.5 to 16.9; p = 0.009), and for none versus any breast-feeding, 1.8 (CI 1.1 to 2.8; p = 0.013). Symptomatic Giardia infection was also associated with lack of breast-feeding (none vs any: incidence rate ratio = 2.5; CI 0.9 to 6.8; p = 0.077), but breast-feeding did not protect against chronic carriage of Giardia. Other significant risk factors for Giardia infection were presence of animals in the household (p = 0.005) and the use of water or nonmilk liquid for infant feedings (p = 0.035). We conclude that breast-feeding protects infants against Giardia by mechanisms that include preventing the establishment of infection.

Human Milk Adiponectin Is Associated with Infant Growth in Two Independent Cohorts

BACKGROUND Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectins oligomeric form. DESIGN AND METHODS This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. RESULTS In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. CONCLUSIONS Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

Efficacy of the Human Rotavirus Vaccine RIX4414 in Malnourished Children

This series is produced by the Health, Nutrition, and Population (HNP) Family of the World Bank’s Human Development Network. The findings, interpretations, and conclusions expressed in this paper are entirely those of the authors and should not be attributed in any manner to the World Bank, to its affiliated organizations or to the members of its Board of Executive Directors or the countries they represent.UNLABELLED The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1% (95% confidence interval [CI], 52.2%-86.2%) and 73% (95% CI, 11.2%-92.3%) for severe RVGE and 60.9% (95% CI, 37.4%-75.4%) and 61.2% (95% CI, 10.4%-83.1%) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination. CLINICAL TRIALS REGISTRY e-Track 444563-006, NCT00385320 (http://www.clinicaltrials.gov).

Human milk adiponectin affects infant weight trajectory during the second year of life.

Objective: Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breast-feeding. We examined infant weight gain in the second year of life after exposure to high or low levels of mothers milk APN. Methods: Breast-feeding mother–infant pairs were recruited in Mexico City and studied for 2 years; 192 infants with at least 12 months’ follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bimonthly (year 2), and World Health Organization z scores were calculated. Longitudinal adjusted models assessed weight-for-age and weight-for-length z score trajectories from 1 to 2 years. Results: Maternal serum APN modestly correlated with milk APN (r = 0.37, P < 0.0001) and infant serum APN (r = 0.29, P = 0.01). Infants exposed to high milk APN experienced increasing weight-for-age and weight-for-length z scores between age 1 and 2 years in contrast to low milk APN exposure (P for group × time = 0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with the rate of weight gain in year 2. Conclusions: High human milk APN exposure was associated with accelerated weight trajectory during the second year of life, suggesting its role in catch-up growth after slower weight gain during the first year of life.

Human Milk α1,2-Linked Fucosylated Oligosaccharides Decrease Risk of Diarrhea Due to Stable Toxin of E. Coli in Breastfed Infants

Breastfed infants have a lower risk of diarrhea than infants fed artificial formula. Human milk components, including oligosaccharides, inhibit pathogens in vitro and are postulated to protect infants from disease. Most human milk oligosaccharides are fucosylated. The fucose terminus may be connected by an a 1,2 linkage catalyzed by a fucosyltransferase produced by the secretor gene (FUT2), or by an α1,3 or α1,4 linkage catalyzed by fucosyltransferases produced by the Lewis gene (FUT3) or other α1,3 transferase genes (FUT4,5,6,7,9) of this family. The secretor and Lewis genes also control expression of the Lewis blood group type (Erney et al. 2000, Henry et al. 1995). Some women are nonsecretors, i.e., they do not secrete 2-linked fucosyloligosaccharides into their milk and other bodily fluids. Even among secretors, however, the expression of milk fucosyloligosaccharides varies significantly (Chaturvedi et al. 2001, Erney et al. 2000, Thurl et al. 1997, Viverge et al. 1990). Enterotoxigenic Escherichia coli that produce stable toxin (ST-E. coli) is a common cause of diarrhea; the ability of stable toxin to cause diarrhea is inhibited by human milk α1,2-linked fucosyloligosaccharides in vitro and in vivo.

Human Milk Secretory Antibodies against Attaching and Effacing Escherichia coli Antigens

Secretory immunoglobulin A (sIgA) is a primary factor responsible for preventing attachment of enteropathogens to gut epithelium in breastfeeding infants. We compared the frequency of sIgA to major surface antigens of enterohemorrhagic Escherichia coli (EHEC) in milk of 123 women from the United States and Mexico to determine whether regional differences existed in the frequency of antibodies to these surface antigens. In both groups of women, milk commonly has sIgA against various EHEC lipopolysaccharides, EspA, EspB, intimin, and less frequently against Shiga toxin. The study suggests that persons living in the U.S. are exposed to attaching/effacing enteropathogens more frequently than is generally assumed. The low frequency of antibodies to Stx1 (in 12% of Mexican and in 22% of U.S. samples) suggests that the rare appearance of hemolytic uremic syndrome in adults is not due to neutralization of toxin at the gut level. Only anti-EspA is found in most milk samples from both populations of women. EspA may represent a useful target for an immunization strategy to prevent EHEC disease in humans.