Characteristics of human milk antibodies and their effect in relation to the epidemiology of breastfeeding and infections in a developing country.
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Biomedical subjects
Publications and source records attributed to J R Cruz.
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Focal group interviews on indigenous perceptions and reported management of childhood diarrhea were conducted in 1987-88 in Guatemala as a part of a prospective epidemiological field study of chronic diarrhea. Six cognitive schemata were identified, each with specific causes, a linked progression of concepts, symptoms, signs, and diagnostic characteristics. Nearly all were related to the humoral theory of disease, including the concept of evil eye. Diarrheal disease was conceptualized in the village as a set of processes which could be either "hot" or "cold" rather than as an unchanging single-symptom entity occupying only one spot on the humoral continuum. Clarification of the temporal relationship between concepts was found to be essential to the understanding of these indigenously-defined schemata. Stool color reflecting humoral theory was the primary concept used in household-level diagnosis. Reported behavior associated with these cognitive schemata (traditional treatments, pharmaceutical and dietary management) showed remarkable constancy, and adhered for the most part to the humoral concept of equilibrium. These included the use of oral rehydration solutions (ORS) and liquids. The applied importance of humoral theory to home-based use of ORS is discussed briefly as is the indigenous definition of dehydration.
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From March 1987 to February 1988, fecal excretion of adenovirus types 40 and 41 and rotavirus serotypes in 194 children (age, 0 to 3 years) from a rural community of Guatemala was monitored. In total, 458 samples taken during 385 episodes of diarrhea and 191 specimens obtained during symptom-free periods were examined by enzyme-linked immunosorbent assay. Fifty-seven children hospitalized because of diarrhea were also studied. Among the rural children, 43 (22.2%) excreted adenovirus types 40 and 41 and 20 (10.3%) shed rotaviruses. Adenovirus types 40 and 41 were associated with 54 (14.0%) illnesses, and rotaviruses were associated with 18 (4.7%) illnesses. Asymptomatic infections with adenovirus types 40 and 41 were documented in nine children and with rotaviruses in two children. Fifteen typeable rotaviruses were identified as serotype 2. In the hospital population, 36 (63.2%) children had viral infections. Rotaviruses were identified in 29 (50.9%) and adenovirus types 40 and 41 were identified in 15 (31.2%) of 48 subjects tested. Dual infections by these viruses were found in eight children. Of 22 typeable strains of rotaviruses, 9 (34.6%) were serotype 1, 12 (46.1%) were serotype 2, and 1 (3.8%) was serotype 3. All the children infected with serotype 2 rotavirus were coinfected with other enteric pathogens, while only three (37.5%) of those infected with rotavirus serotype 1 excreted another pathogen. Adenovirus types 40 and 41 are an important cause of gastroenteritis in both ambulatory and hospitalized Guatemalan children. There seems to be a difference in the pathogenicity among rotavirus serotypes.
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Thymosin alpha 1 was determined in milk samples obtained from 67 Guatemalan women 5 days, and 1-3 and 6-18 months postpartum. All the specimens collected 5 days after delivery contained measurable levels (583 +/- 304 pg/ml) of thymosin alpha 1 but only 33% of those obtained 1-3 months postpartum and none collected thereafter did. Since thymosin alpha 1 has been shown to increase T-cell mediated immunity, and to enhance host resistance to infection, it may play an important role in the maturation of mucosal immunity and host resistance in general in the neonate. This study is the first to document the presence of a thymic hormone in early postpartum milk.
For the purpose of better understanding the epidemiology of acute and persistent diarrhea, 130 infants of a marginal urban area in Guatemala City were studied. The subjects were kept under surveillance by weekly home visits, for periods that varied from three to nine months. The diarrhea episodes were detected and microbiological studies were done in fecal material. Additionally, the children were weighed and measured to determine their nutritional status. The infants suffered, on the average, 5.2 episodes per child annually; 9.4% of all the episodes lasted at least two weeks. The children who were less than six months old had more episodes of persistent diarrhea (0.052/child-month) than the older ones (0.017/child-month), with previous diarrhea morbidity and number of infecting enteropathogens being important factors. Furthermore, a child who had already suffered an episode of persistent diarrhea had a higher probability (relative risk = 2.2) of developing an additional one. Adherent E. coli, Cryptosporidium, toxigenic E. coli and Campylobacter jejuni are the pathogens more commonly associated with persistent diarrhea. Diarrheal illnesses have a deleterious effect on nutritional status, especially persistent episodes, which interfere with gain in weight and length of the children.
Nutritional status (weight-for-age, length-for-age, and weight-for-length) was determined in 678 children aged 0-59 months, admitted to the San Juan de Dios General Hospital in Guatemala City with signs and symptoms of acute respiratory infections. Five hundred and fifty seven (82.2%) cases were bronchopneumoniae; 62 (9.1%) were pneumoniae, and 43 (6.3%) were bronchiolitis. Five hundred and seventy (82.6%) children lived in the urban zones of the capital city and 118 (17.4%) in the municipalities of the Department of Guatemala. Deficit in weight-for-age was found in 188 (27.8%) cases, while 176 (25.9%) showed a deficiency in length-for-age. In terms of weight-for-length, 84 (12.4%) were below -2.00 standard deviations of the reference curve. The children from out of the city showed the highest proportions of malnutrition. Monitoring of nutritional status of hospitalized children with infectious diseases can provide valuable information, not only for their management, but also for parental health education.
A prospective study to assess whether milk IgA antibodies against Escherichia coli heat labile-toxin protect breast-fed children against labile toxin-induced gastroenteritis was carried out among infants of a marginal urban area in Guatemala. One hundred and thirty children were kept under surveillance for diarrhea by periodic home visits. Stool specimens were collected from each child routinely every 2-3 weeks and during diarrheal episodes, to study the excretion of labile toxin-producing Escherichia coli. Milk samples from the children's mothers were obtained concomitantly with the fecal specimens of the infants to be analyzed for anti-labile toxin antibodies. Twenty infections by heat-labile toxin-producing Escherichia coli as a sole agent were documented among breast-fed infants. Nine of these infections resulted in gastroenteritis, while the remaining 11 were asymptomatic. At the time of infection children who became sick were ingesting breast milk with significantly (p = 0.028) lower titers of antilabile toxin IgA than those who remained healthy. Only one of the 8 infected children receiving breast milk with high titers (greater than or equal to 256) of anti labile toxin IgA developed diarrhea, compared to 8 of the 12 subjects being fed milk with low titers (less than or equal to 64) (p = 0.025). This is the first report documenting protection by IgA antibodies in milk against labile toxin-induced gastroenteritis in infected breast-fed infants.
During July 1985 to June 1986, fecal excretion of Cryptosporidium oocysts was determined prospectively in a cohort of 130 infants, aged 0 to 11 months, living in a marginal urban area of Guatemala City, Guatemala. A total of 1,280 stool specimens were examined; 158 of them were collected during episodes of diarrhea, and 1,122 were collected during symptom-free periods, every 2 to 3 weeks, from every child. Of the children, 20 (15.4%) excreted Cryptosporidium oocysts during the observation period. Of the diarrheal episodes, 13 (8.3%) were associated with Cryptosporidium sp. Of the control specimens, seven (0.6%) were positive for oocysts. Most of the infections were documented during the months of February to May, at the end of the dry season. Cryptosporidium infections are very common among Guatemalan infants and are an important cause of diarrhea and weight loss. The introduction of liquid or solid foods in the diets of the children, the presence of domestic animals (dogs, cats, or poultry), and the absence of toilet facilities in the house seem to be important risk factors for infection; also, deficient nutritional status may predispose the infected child to Cryptosporidium-associated illness.
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The concentration of secretory IgA and the levels of IgA specific antibodies against Escherichia coli labile-toxin, Shigella flexneri 6, and rotaviruses were determined in milk samples obtained serially from women during the first 16 weeks postpartum. The mean concentration of secretory IgA followed the expected pattern; the levels of specific antibodies fluctuated in an unpredictable manner and independently of milk secretory IgA content, becoming undetectable in many instances. Under some circumstances, continued breast-feeding may not guarantee continued intake of antibodies against intestinal pathogens by the breast-fed infant.
The concentration in human milk of IgA antibodies against six Salmonella and two Shigella groups were determined in specimens obtained from Swedish and Guatemalan nursing mothers of three different socioeconomic levels. The daily intakes of milk antibodies by their children were also estimated. The results show that the concentrations of specific IgA antibodies in milk vary among the different population groups. There is, however, no difference in daily intake of specific IgA by the children.
The immune response of the mammary gland is dominated by local production of secretory IgA antibodies (SIgA). These milk antibodies, amounting to about 0.5-1 g/day throughout lactation, are directed against food proteins and microorganisms often present in the intestine. This is presumably explained by the enteromammaric link: after antigenic exposure in the Peyer's patches of lymphoid cells they home to various exocrine glands, including the mammary gland. Similarly, lymphoid cells from the bronchial mucosa, may contribute to the antibody-producing cell population in the mammary gland. SIgA antibodies against common foods like cow's milk and soy proteins are regularly found in milk if such proteins are part of the mother's diet. It is possible, but unproven, that milk antibodies can decrease the exposure of the infant's intestinal mucosa to foreign food proteins introduced during continued breast-feeding. Milk SIgA antibodies do not prevent intestinal colonization by microorganisms, against which the milk antibodies are directed. The SIgA antibodies are thought to exert protection primarily by preventing contact between the microorganisms and the mucosal membranes. In this manner, human milk blocks attachment of otitis media-causing strains of pneumococci and H. influenzae to retropharyngeal cells, possibly explaining why breast-feeding may prevent otitis media. Milk antibodies have anti-attachment capacity, but there is also low molecular weight material in the milk with this capacity. It probably consists of analogues to the oligosaccharide receptor for pneumococci on the retropharyngeal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones.