Immature circulating lymphocytes in severely malnourished Guatemalan children.

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.

Natural history of Giardia infection of infants and children in rural Guatemala and its impact on physical growth.

Longitudinal data on Giardia excretion, diarrheal disease, and physical growth during the first 3 yr of life collected more than 20 yr ago in 45 Guatemalan children were analyzed. This report describes the natural history of this infection and estimates its effects on growth. All children had at least one Giardia infection, prevalence and incidence rates reaching 20.2% and 5.3%, respectively by the end of the third year. The mean number of Giardia infections per child increased from 0.7 in the first to 3.6 in the third year. More than 40% of these infections lasted 2-6 wk or more and were commonly associated with diarrhea. Weight velocity was significantly lower in the second year of life in Giardia-infected than in Giardia-negative children (p = 0.03). The duration of Giardia episodes and their association with diarrhea appeared to be the most important factors associated with growth disturbance. Although simultaneous infection with other enteropathogens occurred in many children, our findings suggest that Giardia infection may have independent deleterious effects on children's growth.

PIP: Longitudinal data on Giardia excretion, diarrheal disease, and physical growth during the 1st 3 years of life collected more than 20 years ago in 45 Guatemalan children were analyzed. This report describes the natural history of this infection and estimates its effects on growth. All children had at least 1 Giardia infection, prevalence and incidence rates reaching 20.2% and 5.3%, respectively by the end of the 3rd year. The mean number of Giardia infections per child increased from 0.7 in the 1st year to 3.6 in the 3rd year. More than 40% of these infections lasted 2-6 weeks or more and were commonly associated with diarrhea. Weight velocity was significantly lower in the 2nd year of life in Giardia-infected than in Giardia-negative children (p=0.03). The duration of Giardia episodes and their association with diarrhea appeared to be the most important factors associated with growth disturbance. Although simultaneous infection with other enteropathogens occurred in many children, the findings suggest that Giardia infection may have independent deleterious effects on children's growth.

Abnormal behavior and low developmental test scores in iron-deficient anemic infants.

The relationship between abnormal behavior and poor developmental test performance was analyzed in 68 6- to 24-month-old Guatemalan babies with and without mild iron deficiency anemia. Regardless of age, the 10 anemic infants with abnormal affective responses during developmental testing had very low mental scores (mean = 65.7 +/- 5.2 SEM), while the 18 with normal affect had mental scores (mean = 97.1 +/- 4.5 SEM) which were normal by U.S. standards and comparable to the nonanemic group's scores. Five anemic infants with pervasive behavioral disturbance, who showed abnormal orientation to tasks in addition to disturbed affect, did poorly on the motor test (mean = 59.8 +/- 6.2 SEM). Those anemic infants who were normal in task orientation achieved motor scores similar to those of the nonanemic control group. The observed behavioral disturbances are consistent with biochemical evidence concerning the role of iron in the metabolism of central nervous system neurotransmitters which influence affect and arousal. These results suggest that poor mental developmental test performance in infants with iron deficiency anemia may be mediated by disturbances in affective behavior.

Epidemiology of rotaviruses in a cohort of 45 Guatamalan Mayan Indian children observed from birth to the age of three years.

A cohort of 45 children was observed from birth to three years of age in their natural ecosystem to determine patterns of infection, morbidity, and growth. Data from enzyme-linked immunosorbent assay analysis for rotavirus of 5,891 extracts (kept frozen since 1964-1969) of weekly fecal specimens were compared against growth, morbidity, and specimen data files, permitting a retrospective description of the epidemiology of rotavirus infection in the cohort. Rotavirus infections were uncommon in the first months of life in intensively breast-fed infants. Infection increased with age to reach a maximal rate in the six- to 18-month age period. While there was a high incidence of diarrhea in the cohort, rotavirus was associated with only 10% of such episodes. The incidence of rotavirus infection was 1.2 episodes per child-year, and the incidence of rotavirus-associated diarrhea was 0.8 episodes per child-year. Serious outbreaks of rotavirus generally occurred from September through December, with as many as one-half of the children becoming infected. Repeated rotavirus infection was a common phenomenon.

Natural history of rotavirus infection in the children of Santa María Cauqué.

A prospective observation of 45 cohort children from birth to three years of age permitted the collection of 5689 weekly stool specimens, along with frequent morbidity, dietary and growth data. Specimens tested by the ELISA showed that all children became infected with rotaviruses during the first three years of life, many repeatedly. The overall rotavirus incidence was 10.6 per 100 child-months (or 1.3 infections per child per year). Rotaviruses exhibited a high pathogenic potential estimated in 65%, but only about 10% of all diarrheas appeared associated with them. Rotaviruses occurred throughout the year but clustering was evident in August through December, with epidemics of greater severity in particular months of certain years. During outbreaks, from a third to one half of all children became infected with rotaviruses in a given month. This and the frequent association of rotaviruses with other enteric agents (34%) suggest that fecal-oral transmission is the main source of infection, a net result of the prevailing low socioeconomic level in the village setting.

Effect of periodic antiascaris and antigiardia treatment on nutritional status of preschool children.

One hundred fifty-nine children aged 24 to 61 months with 60% ascariasis prevalence and 21.5% giardiasis prevalence in rural Guatemala were studied prospectively for 1 yr. They were divided into four groups comparable for age, sex, socioeconomic status, and past growth experience as judged by slopes of height and weight on age. Each group was randomly assigned to the following 2-monthly treatment regimens: group I, placebo, group II, piperazine, group III, metronidazole; group IV, piperazine and metronidazole. Height and weight were measured every 3 months and stools were examined for parasites every 4 months. Piperazine administration decreased the prevalence of ascariasis to 33.8% at the end of the study but growth remained unaltered. Metronidazole administration decreased the prevalence of giardiasis to 2.5% at the end of the study and was accompanied by increased growth as judged by delta weight, delta % weight for age, slope of weight on age, delta height, delta % height for age and slope of height on age. It is suggested that failure of antiascaris treatment to enhance growth in this study may be because of 1) absence of severe malnutrition in the subjects, 2) adequacy of dietary protein, 3) possible low worm load, and 4) failure to eradicate ascariasis. The findings suggest that giardiasis is associated with reduced growth in preschool children.

Studies on human milk III. Secretory IgA quantity and antibody levels against Escherichia coli in colostrum and milk from underprivileged and privileged mothers.

We studied the milk content of secretory IgA (SIgA) and of specific IgA antibodies to E. coli in relation to volume, in 24 h samples from mothers belonging to different socio-economic groups and living under different ecologic conditions in Ethiopia, Guatemala and Sweden. There were no statistically significant differences in the daily output of milk SIgA among the population groups investigated at different times after onset of lactation. There was, however, a certain trend towards lower SIgA levels among the Guatemalan poor women, compared to the corresponding privileged one (Tables 2 and 3). Three days after delivery the underprivileged Ethiopian mothers showed significantly lower antibody levels than the privileged Ethiopian. These differences were no longer seen when the values were corrected for differences in volume (Table 5). One month after delivery, the levels of SIgA antibodies in milk from Swedish women and Guatemalan privileged women, against a pool of eight E. coli somatic antigens were comparable; these two groups of mothers had significantly higher antibody levels than the Guatemalan rural and urban ones (Table 4). The same pattern was observed after correction for differences in 24 h volumes (Table 5). At 3 months after delivery, the Guatemalan urban privileged women, again showed higher levels and daily output of antibodies against the E. coli antigens than the urban poor and rural mothers (Tables 4 and 5). The milk samples taken from a population where malnutrition is evident, i.e., mothers from Santa María Cauqué, did not show any changes in the levels of SIgA and the anti-E. coli antibodies 3, 6, 9 months after initiation of lactation. The data presented here provide evidence that chronically malnourished mothers are able to produce SIgA and transfer it to their offspring via breast milk. Furthermore, they do so in quantities that are comparable to those observed in well-nourished populations. There was a wide range of concentrations and daily output of SIgA and of specific antibodies in all groups, suggesting that some of the infants get less than others. The observed differences in levels of antibodies against E. coli may be explained by differences in exposure to E. coli strains of the eight serogroups studied here. The possibility of a deficiency in the SIgA antibody response in the undernourished mothers still remains unanswered.

The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants.

To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic group's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.

Food antibodies in milk from Guatemalan women.

PIP: This study investigates the presence of antibodies against food products in milk samples from 30 Guatemalan women of 3 different socioeconomic status: 10 rural poor, 10 urban poor, and 10 urban privileged. The 3 groups had varied dietary habits. Both the rural and urban poor mothers do not consume cow's milk. Black beans are consumed more often by the urban groups while soy bean products are consumed by both rural and urban poor regularly. Milk samples were collected from the mothers. The volume of milk produced in a 24-hour period was estimated by weighing the children before and after every meal. The enzyme-linked immunosorbent assay (ELISA) described by Sohe-Akerlund et.al. was used in quantitating milk secretory immunoglobulin A (SIgA). A modification of the ELISA method was used to determine levels of specific IgA antibodies directed against cow's milk, black beans and soybeans. The Wilcoxon rank sum test was used in statistical analysis. Comparable amounts of SIgA were produced by the 3 groups of mothers in a 24-hour period (p0.1). The urban privileged mothers exhibited significantly higher antibody levels against cow's milk (p0.01) and black beans (p0.05) compared to the other 2 groups. There were no differences in the level of anti-soybean antibodies among the 3 groups. The notion that antibodies found in the breast milk reflect the mother's intestinal antigenic experience is supported by this study. It has been suggested that anti-food protein antibodies contribute in the prevention of allergies. If so, cow's milk fed among the rural and urban poor children may be expected to produce negative reactions. This negative reaction can be prevented by feeding the mother, before delivery, cow's milk products to induce them to produce milk antibodies against cow's milk.^ieng

Serum opsonic activity in acute protein-energy malnutrition.

Phagocytic host defence mechanisms require both normally functioning cells and humoral factors. For example, activated complement components and/or specific immunoglobulin are essential for effective ingestion and killing of bacteria by neutrophils, and complement is especially important early in infection, before specific antibody has been produced. Abnormalities of serum complement have previously been reported in malnutrition, and the present study investigated the levels of serum opsonins in children with protein-energy malnutrition (PEM).Opsonic activity for Escherichia coli and Staphylococcus aureus was depressed in acute PEM patients, but recovered to higher levels with treatment. This depression was detected only when low concentrations of serum (10-20 ml/litre) were used. Marked and persistent opsonin deficiencies were associated with poor clinical response. Reduced opsonic activity may adversely affect host defence mechanisms and contribute to morbidity and mortality from pyogenic infections in PEM. Replacement therapy with fresh or fresh frozen plasma might restore opsonic activity in these patients and reduce the risk of septicaemia and its attendant high mortality.

Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.

A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.

Prevalence of maternal and neonatal infections in a developing country: possible low-cost preventive measures.

The frequency and duration of infectious illnesses in 408 pregnant rural women and 417 poor urban infants in Guatemala have been investigated, together with morbidity and mortality among the offspring of the rural women. Rural women suffered high rates of infection during the gestation period. Symptomatic illnesses, mainly acute respiratory infection and diarrhoeal disease, usually showed a higher incidence during the last months of pregnancy. Significant bacteriuria was identified in 21% of the women, though symptoms of urinary tract infection were found in about 25%. Vaginal infection was found in 38% of women at the beginning of pregnancy and in 79% at its end. Twelve per cent of women showed evidence of reactivated infections with cytomegalovirus, herpes simplex virus and Toxoplasma gondii. The neonatal mortality rate in the rural population was 37.7 per 1000 liveborn infants. Most deaths were among preterm babies. Significant bacteriuria was related to low birth weight. Morbidity in rural neonates was also high, but the illnesses were not severe and had a short duration. Neonatal morbidity in poor urban infants was also high. Breast-feeding had a protective effect: breast-fed rural and poor urban infants had a lower incidence of illness than urban babies who were not breast-fed. The influence of infection during pregnancy on the conceptus and some low-cost measures for reducing it are discussed. Measures for decreasing neonatal morbidity in rural and poor urban ureas are proposed.

Secretory antibody directed against rotavirus in human milk--measurement by means of enzyme-linked immunosorbent assay.

Human milk contains antibodies to a variety of enteropathic agents. We utilized the method of enzyme-linked immunosorbent assay to investigate anti-rotavirus secretory IgA in 113 human milk and colostral specimens from a rural area in Guatemala, 32 colostral specimens from an urban area of Costa Rica, and 12 from an urban area of the United States. Anti-rotavirus SCIgA was found in all colostral samples and in 94% of the milk specimans. Both the absolute concentration of anti-rotavirus SCIgA and concentration relative to total SCIgA were highest in colostrum, falling to lower but detectable levels from one week to two years after birth. No significant differences were noted in the results from the specimens from the three different geographic areas. The possible role of this antibody in immunity to rotavirus infections is discussed.

Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay.

To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.