TABLE 9 Incidence of Pathogenic Parasites 45 Cohort Infants, Birth to Age Three Years, by Six-Month Intervals
Months |
||||||
Parasite |
0-5 |
6-11 |
12-17 |
18-23 |
24-29 |
30-35 |
E. histolytica |
5a |
0 |
6 |
9 |
12 |
5 |
(5)b |
(11) |
(20) |
(32) |
(37) |
||
D. fragilis |
0 |
3 |
1 |
1 |
1 |
5 |
(3) |
(4) |
(5) |
(6) |
(11) |
||
G. intestinalis |
8 |
13 |
14 |
4 |
1 |
2 |
(21) |
(35) |
(39) |
(40) |
(42) |
||
A. Iumbricoides |
4 |
9 |
14 |
14 |
1 |
0 |
(13) |
(27) |
(41) |
(42) |
(42) |
||
T trichiura |
2 |
2 |
4 |
6 |
3 |
3 |
(4) |
(8) |
(14) |
(17) |
(20) |
||
H. nana |
0 |
0 |
0 |
1 |
3 |
2 |
(4) |
(6) |
a
Number of children with parasite
b (Accumulated
number of children with parasite)
Source: Mata (1978a);
Melvin and Mata (1979)
TABLE 10 Duration of Shigella Infection (Cases and Carriers) 45 Cohort Infants, Birth to Age Three Years
Weeks of Duration |
|||||||
Shigella Subgroup |
No. of Episodesa |
1 |
2-4 |
5-8 |
9-12 |
13-16 |
17-38 |
dysenteriae |
29 |
7 (24)b |
10 (34) |
4 (14) |
3 (10) |
2 (7) |
3 (10) |
flexneri |
5 |
18 (24) |
21 (28) |
18 (24) |
9 (12) |
5 (7) |
4 (5) |
boydii |
21 |
14 (67) |
6 (28) |
1 (5) |
|||
sonnet |
7 |
7(100) |
|||||
Total |
132 |
46 (35) |
37 (28) |
23 (14) |
12 (9) |
7 (5) |
7 (5) |
a
Two isolations were considered independent if separated by more
than 2 weeks.
b Number of
events (percentage within Shigella subgroup)
Source Mata (1978a)
TABLE 11 Enteric Pathogens in 381 Cases of Diarrhea Experienced by 22 Cohort Children from Birth to Age Three Years.
Agenta |
Number Positive (%) |
Giardia intestinalis |
92 (24.1) |
Shigella spp. |
89 (23 3) |
Rotavirusesb |
44 (11.5) |
Entamoeba histolytica |
44 (11.5) |
Adenoviruses (cultivatable) |
29 (7.6) |
Salmonella spp. |
11 (2.9) |
Enteropathogenic Escherichia coli |
6 (1.6) |
Dientamoeba fragilis |
3 (0.8) |
One or more of the above |
227 (59.6) |
a
Strains of Escherichia cold [enterotoxigenic (ETEC),
enteroinvasive (EIEC), enterohemorrhagic (EHEC), and
enreroaggregative (EAggEC), Campylobacter, Cryptosporidium,
diarrhea adenoviruses, and small round structured viruses were
not investigated at the time of the Cauqué, Study
b Rotaviruses
were studied in stored frozen specimens (Mate et al., 1983).
Source: Mata et al. (1984)
TABLE 12 Incidence of Rotaviruses in Diarrhea of Children Living in Contrasting Ecosystems
Population |
Child-Years |
All Diarrhea |
Rotavirus Diarrhea |
Rotavirus Infection |
% Diarrhea Due to Rotavirus |
Canquéa 1964-1969 |
132.5 |
1,050 (7.9) |
109 (0.8) |
166 (1.2) |
10.4 |
Matlaba 1978-1979 |
120 |
727 (6.1) |
34 (0.3) |
- |
4.7 |
Winnipegb 1976-1979c |
139 |
165 (1.2) |
40 (0.3) |
50 (0.4) |
80.0 |
a
Rural poor, adjusted to account for uncollected or unavailable
specimens (Mate et al., l 983)
b Recalculated
from Black et al. (1982a)
c Adapted from
Gurwith et al. (1981)
Effect of Infection on Food Intake and Growth
Frequent symptoms and signs in children were despondency, prostration, fever, anxiety, and anorexia. These are common manifestations of stress triggered by interleukins and tumor necrosis factor released by macrophages in response to infection (Beisel 1977; Dinarello, 1984). The main nutritional consequences of infection are reduced consumption of calories; loss of ingested foods; increased transit of food through the alimentary canal; altered digestion and absorption; protein-losing enteropathy; loss of electrolytes, vitamins, and other nutrients; altered metabolism; sequestration of trace elements; and nutrient diversion (Beisel, 1977).
Canqué children ate less food during episodes of infectious diseases, regardless of etiology, severity, or target organ. The effect was more pronounced with fever, sepsis, diarrhea, and lower respiratory infection. Thirty-three percent of children with whooping cough consumed only one-half of the customary amount of tortilla in the first month of illness; maize intake was also significantly depressed in the second and third months of the disease (Table 14).
Fully weaned children consumed an adequate amount of food when they were free of disease. However, intake fell below recommendations when they acquired enteric, skin, and lower respiratory infections (Figure 7) (Mate et al., 1977; Mata, 1979). The average decrease attributed to diarrhea alone was 24% for total protein and 21% for calories (Mate, 1983b). In Uganda, the mean reduction of intake in children consequent to infection was 48% (Whitehead, 1901). Food restriction is worsened by the traditional custom of withholding food during illness (Scrimshaw et al., 1968). Fortunately, much of the absorptive capacity of the mucosa remains intact during enteric infection, permitting feeding during illness and convalescence (Molla et al., 1982).
TABLE 13 Incidence of Selected Infectious Diseases and Symptoms Experienced by 45 Cohort Children, Birth to Age Three Years
Diseases, Symptomsa |
Cases |
Percent of All Cases |
Rate per 100 Person-Yearsb |
|
Diseases |
Respiratory |
|||
Bronchitis |
256 |
10.5 |
193.9 |
|
Bronchopneumonia |
70 |
2.9 |
52.0 |
|
Tonsillo-pharyngitis |
10 |
0 4 |
7.6 |
|
Enteric |
||||
Diarrhea |
640 |
26.1 |
484.8 |
|
Diarrhea with mucus |
313 |
12.8 |
237.1 |
|
Dysentery |
97 |
4.0 |
73.5 |
|
Mouth |
||||
Herpes simplex, primary |
20 |
0.8 |
15.1 |
|
Stomatitis |
23 |
0.9 |
17.4 |
|
Thrush |
28 |
1.1 |
21.2 |
|
Glossitis, cheilitis |
14 |
0.6 |
10.6 |
|
Skin, scalp |
||||
Impetigo |
31 |
1.3 |
23.5 |
|
Abscess, furuncle |
16 |
0.7 |
12.1 |
|
Common communicable |
||||
Measles |
32 |
1.3 |
24.2 |
|
Rubella |
15 |
0.6 |
11.4 |
|
Chicken pox |
26 |
1.1 |
19.7 |
|
Febrile exanthem |
25 |
1.0 |
18.9 |
|
Whooping cough |
10 |
0.4 |
7.6 |
|
Other |
||||
Fever of unknown origin |
14 |
0.6 |
10.6 |
|
Symptoms |
Fever, 37.5+ C |
1,148 |
25.7 |
869.7 |
Diarrhea, all |
1,205 |
27.0 |
912.7 |
|
Vomiting |
235 |
5.3 |
178.0 |
|
Anorexia |
823 |
18.4 |
623.5 |
|
Despondent, irritable |
1,008 |
22.6 |
763.6 |
a
Twenty-four diagnoses had fewer than 10 cases each and were
omitted from the table.
b 132
person-years of experience. taking attrition into account
The deleterious effect of infection on nutrition is reflected in lower body weight and height. Male child No. 12, born with some weight deficit, had normal growth velocity during exclusive breast-feeding (Figure 8). Enteroviral infections and mild respiratory illnesses in that period had no apparent clinical impact. But with increasing morbidity from 6 to 27 months (weaning), the curve flattened, particularly from the second to the fifth semesters. Most cohort children behaved like child No. 12: they became malnourished in the second semester until the end of the second year or longer. Weight increments improved in the third year of life for some, but not all, children.
TABLE 14 Consumption of Tortillas During Whooping Cough by 21 Cauqué Children Two to Three Years Old
Percent Consumed by
Month Ill |
||||
Child Number |
Age (months) |
1st |
2nd |
3rd |
22 |
41 |
43b |
84 |
108 |
54 |
36 |
93 |
79 |
82 |
37 |
38 |
41 |
94 |
94 |
52 |
35 |
108 |
109 |
149 |
59 |
35 |
130c |
200 |
200 |
76 |
31 |
94 |
90 |
92 |
11 |
44 |
133 |
111 |
102 |
16 |
44 |
110 |
122 |
142 |
35 |
39 |
98 |
45 |
105 |
24 |
41 |
52 |
109 |
105 |
23 |
41 |
95 |
54 |
90 |
31 |
41 |
96 |
122 |
117 |
69 |
31 |
99 |
91 |
97 |
83 |
29 |
55 |
39 |
103 |
91 |
26 |
100 |
100 |
60 |
49 |
36 |
78 |
80 |
69 |
34 |
38 |
139 |
57 |
80 |
88 |
27 |
98 |
89 |
98 |
80 |
29 |
100 |
91 |
100 |
94 |
27 |
113 |
154 |
224 |
18 |
42 |
33 |
36 |
74 |
a
Percent consumption in relation to intake before onset,
considered as 100%
b Reduction by
more than 50% of usual intake
c Increase by at
least 25% of usual intake
Source: Mata (1978a)
The age of the child and the type of feeding influenced the effect of infection on growth. For instance, whooping cough was of less nutritional consequence during exclusive breast-feeding (Figure 9, children No. 214 and 216) than in the protracted weaning period (Figure 9, children No. 172, 177, and 181). Girl No. 177 lost almost 2 kg in two weeks, which she could not recover until 16 weeks later. She caught up to preinfection weight after about 36 weeks, but was still further below the mean weight for village children by this time.
The nutritional effect of infection was worse if there was underlying fetal growth retardation or prematurity, illustrated for two children with different birth weights (Figure 10). All diarrhea episodes in the first two years of life were associated with some stagnation of linear growth, and this was greater and more prolonged in the child who had been born with greater fetal growth deficit (Mate, 1982b).
Infectious diseases were efficient killers of infants who were either born small-for-gestational age or prematurely. For instance, female child No. 19, born with deficient weight but growing satisfactorily under exclusive breast-feeding (Figure 11), developed respiratory infection and anorexia at 9 weeks of age and meningitis at 13 weeks, which lasted 6 weeks. These events were associated with 12 weeks of weight faltering. The child continued at the breast, with supplementary food, and caught up somewhat (oddly, after diarrhea and varicella). However, growth deteriorated shortly thereafter, coinciding with attacks of stomatitis, diarrhea, and respiratory infection. The child developed severe psychomotor retardation and malnutrition, and died at the end of her second year of life. The infection-malnutrition complex can kill children who have survived the perilous weaning period. For instance, child No.44, discussed above (see Figure 8), reached school age but succumbed to typhoid fever at seven years of age. Other examples of infection-nutrition interactions in the 45 cohort children were described elsewhere (Mate, 1975, 1978a, 1982b, 1983a,b,c, 1985, 1990, 1992; Mata et al., 1971, 1972a,b, 1975, 1976b, 1977, 1982, 1984).
Growth and Development of Under-Fives
The distribution of 430 Cauqué, singletons, by birth weight and gestational age in the Lubchenco grid, revealed fetal growth retardation for all types of newborns (Figure 12). The large shaded area in Figure 12 identifies small-for-dates infants (33% of the total). The smaller area (7%) identifies premature babies (Mate, 1978a). The total of these subpopulations equaled 42% of he singletons. The remaining infants were adequate for gestational age, although of smaller size than newborns from well nourished women. The relative distribution of low birth weight and small for-dates infants did not vary over the nine years of study.
This population of small and malnourished neonates evolved into small and stunted children, as seen in the mean weight curve of Canqué girls and boys, during the first three years of life, in comparison with the standard (Figure 13) (Mate, 1 978a). Weight gain was stereotyped: it was adequate during exclusive breast-feeding, departed from the reference curve there after, and showed marked deficits from one to three years of age. The same behavior was seen for height and for circumference of head and thorax. Children tended to remain within growth tracks defined at birth, with the largest children growing better postnatally, and the smallest ones growing more slowly during infancy and preschool age (Figure 14) (Mate, 1 978a). The same was seen with the other anthropometric variables.
FIGURE 12Distribution of 430 singleton infants by birth weight and gestational age, in the Lubchenco grid. Figures are the number of infants within each compartment. Three shaded areas are marked: two of infants less than 37 weeks of gestation (premature, of which the largest (less than 2 kg) were the most immature. One large area brackets the babies born at term, with less than 2.5 kg, namely, the "small-for-gestational age." These two groups of babies accounted for 42% of the total delivered during the study period (Mate, 1978a).
There was a significant correlation between birth parameters and postnatal growth, but only a small part of the variance of physical growth was explained by weight and height at birth. Small girls grow into stunted women, who deliver small babies. The interruption of the intergeneration cycle would require breakage of the infection-malnutrition interaction in childhood, through control and prevention of infections.
Individual growth curves were fitted by the regression equation y = a + bx + c log x used to fit cross-sectional data (Malcolm, 1970), where a is the intercept, an estimate for age 0; b is the linear parameter, reflecting most of the growth after growth deceleration; and c is the parameter of growth in the first months. The fitting gave R2 values as high as 0.99. Stepwise regression analysis of fitted physical growth showed that higher maternal weight, lower maternal age, fewer deliveries, lower weaning age, and smaller number of days with respiratory infections correlated with faster growth in the first months of life (Mate, 1978a).
By stepwise regression for parameter c (child growth in early months), days of respiratory disease, maternal weight, young maternal age, number of deliveries, weaning age, and fewer days of respiratory infection were positively correlated. In a multivariate analysis, days of respiratory infection in infancy were negatively correlated with growth in the first months, explaining 19% of the variance. Maternal age was negatively correlated, adding 14.5%. Birth length and maternal weight also explained part of the variance. These four variables accounted for 48.7% of the total variance of early child growth (Mate, 1978a). Young women had infants who grew faster in the first months, whereas older mothers had infants who grew more slowly. Premature infants, as a whole, had adequate growth velocities while they remained at the breast.
Regarding parameter b weaning age accounted for 16.3% of the variance of linear growth by stepwise multivariate analysis. Other variables contributing significantly to explaining delayed linear growth were short birth interval, maternal height, rate of Entamoeba histolytica infection, fewer deliveries, and rate of infection with Shigella flexneri. This evidence indicated the need to improve the condition of the mother and the sanitary environment, in order to boost nutrition of young girls, pregnant women, and other women of reproductive age.
With regard to psychomotor development, most Cauqué, newborn infants appeared adequate at birth, as noted for other Cakchiquel infants (Wug de León et al., 1964). With adapted scales (Cravioto et al., 1966), Canqué infants showed adequate psychomotor development in the first semester of life. Thereafter, deficits became evident, and an evaluation of six- to seven-year-olds of the 1964 and 1965 cohorts, aided by the bilingual teacher of the village, showed a lower performance as compared to urban children. The lack of marked individual variation among children suggested that deficits probably reflected the influence of the "village environment" on all children. As adolescents and adults, Canqué Indians used a rich vocabulary to describe and interpret the weather, agriculture, handicrafts, health, and other aspects of village life, a vocabulary in some ways richer than that of Spanish-speaking mestizo and caucasians of Central America.
Malnutrition and Adaptation
The main deficiencies of nutrients in the village were calories, good quality protein, iron, and some vitamins and micronutrients. Iron deficiency in the absence of malaria and hookworm is explained by exceedingly high rates of infection that are associated with sequestering of free serum iron, coupled with the low bioavailability of iron in the predominantly vegetarian diet. Interestingly, most of the anemia disappeared without specific treatment by the fourth year of life, probably when children became immune to the infections prevailing in the village, and when their food consumption improved (Mate, 1978a). No hypoproteinemia was found in Cauqué, children except after severe infections (Viteri et al., 1973). Xerophthalmia, keratomalacia, and blindness attributable to vitamin A deficiency were not found during the study. Fruits and vegetables supplied sufficient carotenes and ascorbic acid. There was sufficient exposure to sunlight to prevent vitamin D deficiency. Iodine deficiency had been corrected by the iodination of table salt (Ascoli and Arroyave, 1970). No longitudinal studies of biochemical and endocrine functions were carried out.
Severe infectious diseases diminished food intake, caused nutrient losses, and altered metabolism, aggravating chronic malnutrition or precipitating its acute forms. There were 32 cases of edematous protein energy malnutrition in children under five during the study period (9 prekwashiorkor, 10 kwashiorkor, and 13 marasmic-kwashiorkor), which appeared a few weeks after the occurrence of diarrhea and other infectious diseases (Figure 15). Most cases appeared from May to September-the rainy season-the period of greater incidence of diarrhea, measles, and other communicable diseases. Paradoxically, this was the period of better supplies of local foods (maize, green leaves, fruits), greater cash income from selling produce, and increased availability of firewood for cooking. There were few or no cases of edematous malnutrition in the drier months (February, March, April, November, and December).
Infant Survival and Mortality
Maternal factors were the main determinants of infant growth and size at birth, and correlated strongly with child survival. Low birth weight infants had lower infant survival than those of normal birth weight. A birth weight greater than 2,750 g correlated with absolute infant survival, regardless of postnatal events, such as measles, dehydrating diarrhea, or deficient diet (Table 15). Exclusively breast-fed infants who weighed at least 2,000 g at birth survived the first week of life; if they weighed at least 2,750 g at birth, they survived the first three months of life; if they weighed at least 3,000 g at birth, they survived the first semester (see Table 16). Similar behavior was seen in cohorts defined by gestational age. LBW accounted for more than 70% of the total infant mortality in Cauqué, just as in modern societies with low infant mortality (Mata,1982b). Prematurity was the main predictor of low infant survival, but such risk was not evident after the first year of life; that is, premature infants who survived infancy did not die thereafter (Mata, 1978a). Low birth weight infants also had low survival, an effect carried on into the second, third, and fourth years of life (Table 16).
These data show the urgent need to reduce the incidence of low birth weight infants as a necessary step to reduce mortality in children under five. Almost all 18 neonatal deaths occurred in premature babies and were attributed to antenatal causes that are also typical of modern societies. With postneonatal fatalities, all but two "crib" deaths and one undetermined death were attributed to infectious diseases (Table 17). Lower respiratory disease accounted for almost half the deaths in the postneonatal infant period, followed by diarrhea and measles. Whooping cough, pneumonia, measles, and diarrhea were related to two-thirds of the deaths in the second year. The enhanced risk of death due to infection in the second year had been recognized (Gordon et al., 1967). Had the population been vaccinated-a utopian hope at that time-19 of the 58 deaths (33%) would have been spared. Medical treatment at the Health Clinic most likely averted many deaths from diarrhea and other infectious diseases, as evidenced by the progressive reduction of mortality through the study period.
Paradigm of Infection-Malnutrition
The evidence furnished by the Cauqué, study (Mate, 1 978a), complemented by observations in Costa Rica (Mate, 1982b, 1983c), identified infections as the main cause of malnutrition, growth retardation, and premature death (Figure 16). This is quite evident for diarrhea! disease, unless proper therapy is aggressively implemented, meaning rehydration, proper feeding, and adequate drugs, when indicated. The effect of infection on nutrition seems stronger than that of the nutritional state on the outcome of infection. In Figure 16, the directions and widths of the arrows illustrate the causality and intensity of the associations.
FIGURE 15Accumulated incidence of edematous energy-protein malnutrition, by month of year, Santa María Canqué, 1964-1972. There were 32 cases, 72% of which appeared from May through September. This is the rainy season, and the months of infectious diseases. Also, they are months of relatively greater availability of food, firewood, and money. Edematous malnutrition was not observed or was infrequent from October through February. Cases were similar for both sexes, and the case fatality ratio was 15.6% (Mate, 1978a).
TABLE 15 Survival During Infancy, by Birth Weight, Among 430 Canqué Singletons, 1964-1973
Birth Weight, g |
|||||||||||
Time Survived |
No.of lnfants |
1,000- |
1,500- |
2,000- |
2,250- |
2,500- |
2,750- |
3,000- |
3,250- |
3,500- |
Total |
24 hours |
430 |
4/5a (80) |
25/28 (89) |
47/47 (100) |
99/99 (100) |
125/125 (100) |
82/82 (100) |
31/31 (100) |
11/11 (100) |
2/2 (100) |
426/43 (99) |
7 days |
430 |
4/5 (80) |
23/28 (82) |
47/47 (100) |
99/99 (100) |
125/125 (100) |
82/82 (100) |
31/31 (100) |
11/11 (100) |
2/2 (100) |
424/430 (99) |
28 days |
429 |
2/5 (40) |
22/28 (79) |
45/47 (96) |
96/99 (97) |
123/125 (98) |
82/82 (100) |
30/30 (100) |
11/11 (100) |
2/2 (100) |
413/429 (96) |
3 months |
429 |
2/5 (40) |
18/28 (64) |
44/47 (94) |
96/99 (97) |
123/125 (98) |
82/82 (100) |
30/30 (100) |
11/11 (100) |
2/2 (100) |
408/429 (95) |
6 months |
429 |
1/5 (20) |
15/28 (54) |
43/47 (91) |
96/99 (97) |
120/125 (96) |
80/82 (98) |
30/30 (100) |
11/11 (100) |
2/2 (100) |
398/429 (93) |
1 year |
428 |
1/5 (20) |
13/28 (46) |
41/47 (87) |
95/99 (96) |
117/124 (94) |
78/82 (95) |
30/30 (100) |
10/11 (91) |
2/2 (100) |
387/428 (90) |
a
Number of survivors/total cases; below, (percentage surviving)
Source: Mata (1978a)
TABLE 16 Relationship Between Growth Retardation and One- to Four Year-Old Mortality, Santa María Canqué, 1964-1972
Mortality, Year of
Life |
||||
Newborn Classa |
1st |
2nd |
3rd |
4th |
Normal |
12 (50) [242] |
9 (44)a [204] |
5 (33) [153] |
1 (8) [122] |
Small-for-Gestational Age |
12 (84) [143] |
8 (76)b [105] |
3 (39) [78] |
3 (50) [60] |
Premature |
16 (516) [31] |
0 |
0 |
0 |
Total |
40 (96) [416] |
17 (52) [324] |
8 (33) [244] |
4 (21) [190] |
a By
birth weight and gestational age combined (see Figure 11)
b Number of
deaths (rate per 1,000 children in the class alive at the
beginning of the period); below [population at the beginning of
the period]. Note: attrition in numbers with age reflects the
lower age of younger cohort children. The 1964 cohort contributed
more children to the table than cohorts born later on.
Source: Mata (1978a),
modified
TABLE 17 Numbers and Relative Percentages of Child Deaths Attributed to Infectious Diseases, Santa María Cauqué, 1964-1972
Age (Years) |
Population at Riska |
Total Deathsa |
Acute Diarrhea |
Measles, Whooping Cough |
Measles, Whooping Cough,
Diarrhea |
<1 |
458 |
41 |
4 (10) |
9 (22)b |
13 (32) |
1 |
400 |
19 |
3 (16) |
13 (68) |
16 (84) |
2 |
323 |
8 |
2 (25) |
3 (38) |
5 (63) |
3 |
258 |
4 |
1 (25) |
3 (75) |
4(100) |
4 |
198 |
0 |
|||
5 |
148 |
0 |
|||
6 |
110 |
0 |
a-Accumulated
during the Cauqué, Study, 1964-1972
b Number of
deaths (relative percentage)
Source: Mata (1978a),
modified
Recurrent infections progressively lead to wastage and stunting. Severe infectious episodes precipitate acute malnutrition and cause death. In turn, some infections impair delayed hypersensitivity and other immune functions (Scrimshaw et al., 1968). Immunosuppression favors infection, closing the vicious circle. These findings support the conclusion that to improve nutrition it is necessary to control and prevent infections.
The control of environment (water supply, sanitation, personal hygiene) is fundamental to reducing diarrhea! disease, and this is a sine qua non to decrease infant mortality (Mate, 1982b).