A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers.

BACKGROUND: Two carotenoids, lutein and zeaxanthin are found in the retinal pigment epithelium of the eye where they are believed to protect it against oxidative and light damage. The amounts of these carotenoids consumed by premature infants are not known. OBJECTIVE: The objective of the investigation was to measure these carotenoids in human and formulae milks. DESIGN: In all, 28 human milk samples were obtained at various times between days 1 and 41 of lactation from 13 mothers. Six formula milks commonly used in hospitals were also analysed. SETTING: Mothers who provided the milk samples had infants in the neonatal ward at the Royal Maternity Hospital, Belfast. RESULTS: Median lutein and zeaxanthin concentrations in human milk were 4.79 (range 0.42-9.98) nmol/g fat and 0.55 (0.00-1.70) nmol/g fat, respectively. Five of the six formula milks also contained lutein and zeaxanthin with concentrations that varied over a wide range (0.7-9.7 and 0.1-1.2 nmol/g fat, respectively). CONCLUSIONS: Carotenoid concentrations usually decreased with the duration of lactation. Some formula milks that were specially formulated for premature infants contained high concentrations of the lutein and zeaxanthin and the source may be egg yolk. SPONSORSHIP: These studies were supported by the University of Ulster and the Northern Ireland Mother and Baby Appeal.

Effects of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis.

BACKGROUND: Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. METHODS: We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. FINDINGS: For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. INTERPRETATION: We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.

Lack of influence of red palm oil on severity of malaria infection in pre-school Nigerian children.

Vitamin A supplements are reported to reduce febrile episodes of malaria and parasite counts, especially in children aged 12-36 months. Red palm oil (RPO) is a good source of vitamin A, is rich in alpha- and beta-carotene and is as effective as high-dose retinyl palmitate supplements in improving vitamin A status. In western Nigeria, where malaria is endemic, RPO is widely used and consumption can be measured using plasma alpha-carotene as a proxy biomarker since there are few other prominent sources of this carotene in the diet. The influence of RPO consumption on malaria was investigated in 207 children (aged 0-60 months) who presented with fever in August-October 1999 at several hospital clinics around Ile-Ife. Medical and anthropometric data, body temperature, parasitaemia and plasma C-reactive protein (CRP), retinol, carotenoids and tocopherols were measured in the children. Mothers were interviewed on usage of cooking oil and mosquito nets in the home, education and occupation. Most families used RPO and median plasma concentrations of both alpha-carotene (0.518 mumol/L) and beta-carotene (0.698 mumol/L) in the children were high. Using body temperature, parasite density and plasma CRP as markers of disease severity, multiple linear regression analysis was carried out on those for whom complete data were available (n = 138), separated into 3 age-groups of < 12 months (n = 37), 12-36 months (n = 68) and > 36 months (n = 33). In the absence of plasma retinol, plasma alpha-carotene explained 13.9% of the variance in parasite density (P = 0.013) but only in children aged > 36 months. The relationship with disease severity was negative, i.e., there was some evidence that RPO usage protected against malaria, and other dietary indices generally indicated that better nutritional status was associated with a lower severity of malaria.

Nutritional factors and visual function in premature infants.

Approximately 5-7% of all infants are born prematurely, and birth before 37 weeks is the most common cause of neonatal mortality, morbidity and long-term disability. Premature infants are poorly equipped for life outside the womb, and oxidant stress has been implicated in the aetiology of visual impairment in these infants, who are often exposed to increased O2 concentrations and high light intensity in neonatal units. The carotenoids lutein and zeaxanthin, which give the macular area of the eye its yellow colour, are located in the retinal pigment epithelium of the eye, and are believed to play a role in protecting it against oxidative and light damage. The macular pigments are of dietary origin, and green leafy vegetables are the primary source of lutein and zeaxanthin. Lutein is one of the five most common carotenoids found in the diet. There is current interest in the macular pigment in relation to age-related macular degeneration, but these pigments may also have a protective role in the retinal pigment epithelium of the newborn infant. Little information is available on blood lutein and zeaxanthin levels in neonates. Levels of lutein in human milk are two to three times higher than those of beta-carotene, whereas their concentrations in the mothers' blood are approximately the same. Human milk is the main dietary source of lutein and zeaxanthin for infants until weaning occurs. The biochemical mechanisms which mediate the transport of the macular carotenoids into the eye are not known, but tubulin has been identified as the major carotenoid-binding protein, and may play a role in the physiology of the macula.

Anthelmintic treatment of rural Bangladeshi children: effect on host physiology, growth, and biochemical status.

BACKGROUND: The effect of helminth infestation on the nutrition, growth, and physiology of the host is still poorly understood. Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements. OBJECTIVE: The objective of this study was to assess the effect of regular deworming on child growth, physiology, and biochemical status. DESIGN: The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2-5 y. Treatment (mebendazole) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo. Weight, height, midupper arm circumference, intestinal permeability, plasma albumin, alpha(1)-antichymotrypsin, and total protein concentration were assessed every 2 mo. RESULTS: Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78% to 8%, of Trichuris trichiura from 65% to 9%, and of hookworm from 4% to 0%. There was no significant difference in the growth of treated children compared with those given placebo tablets. No changes in intestinal permeability or plasma albumin were observed after deworming. Significant decreases in total protein (P<0.001) and alpha(1)-antichymotrypsin (P<0.001) were observed in the treatment group, indicating possible reductions in inflammation and immunoglobulin concentration after deworming. A significant increase in the prevalence of Giardia intestinalis (from 4% to 49%) in the treatment group was associated with a short-term reduction in weight (P = 0.02) and higher intestinal permeability (P <0.001) in infected subjects. No long-term effects of G. intestinalis on growth were observed. CONCLUSION: Low-intensity helminth infections, predominantly of A. lumbricoides and T. trichiura, do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children.

Interpretation of vitamin A status in apparently healthy Pakistani children by using markers of subclinical infection.

BACKGROUND: Plasma retinol concentrations are depressed by infection but are commonly used to assess vitamin A status. OBJECTIVE: We measured 2 acute phase proteins, alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), to determine whether they could be used to assist in interpreting vitamin A status. DESIGN: In 1997, a 2-stage cluster-sampling procedure was used to select 3074 apparently healthy, 6-60-mo-old children from rural and urban areas of North West Frontier Province, Pakistan. Plasma retinol, ACT, AGP, and ferritin measurements and anthropometric measurements were obtained for 2519 children. RESULTS: Median plasma retinol, ACT, AGP, and ferritin concentrations were 0.86 micromol/L, 0.39 g/L, 1.14 g/L, and 5.5 microg/L, respectively. There were no significant (P: > 0.05) differences in retinol, ACT, or AGP by sex or age. Some 797 children (32%) had retinol concentrations <0.7 micromol/L and 87 (4%) had retinol concentrations <0.35 micromol/L; 274 children (11%) had elevated ACT (>0.6 g/L) and 1141 (45%) had elevated AGP (>1.2 g/L). Retinol concentration correlated with ACT (r = -0.141), AGP (r = -0.138), and ferritin (r = -0.09) (all P: < 0.001), but stepwise multiple regression indicated that these 3 variables made a minimal although quantifiable contribution to the variance of retinol (ACT, r(2) = 0.02; all 3 variables, r(2) = 0.03). CONCLUSIONS: The transient depression in plasma retinol produced by subclinical infection increased the number of at-risk children by 10% (76 of 797) and 56% (49 of 87) for plasma retinol concentrations <0.7 and <0.35 micromol/L, respectively. In addition, dietary inadequacy may be responsible for retinol concentrations being approximately 16% lower in Pakistani children than in children in the United Kingdom, where dietary vitamin A is adequate.

Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants.

Gut integrity, which can be measured by the urinary lactulose:mannitol excretion test, deteriorates with the introduction of weaning foods. In The Gambia, gut integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was least impaired from April to June. This coincides with the time of year of maximum vitamin A (VA) intake-the mango season. Subsequently, two VA intervention studies were done in infants in India. Eighty infants attending a community health center received 16,700 IU weekly or placebo. In another study, 94 hospitalized infants were given 200, 000 IU VA or placebo: 31 received VA on admission, while the rest (32 VA, 31 placebo) received treatment on discharge. All VA-treated groups had more rapid improvement in gut integrity than the placebo groups, but no group had gut integrity normalized by Western standards. The data suggest that VA status may influence gut integrity.

Parasites.

Ill health related to food-borne infection transcends all geographical, political and cultural boundaries. The incidence of food-borne diseases continues to adversely affect the health and productivity of populations in most countries, especially non-industrialised ones. However, since the 1950s, the emphasis in the industrialised world had shifted away from addressing public health problems, to problems of chemical contaminants etc., but recently food-borne infections have again become of increasing concern to governments and the food industry. Improvements in international transportation means food can be distributed throughout the world, but so can the parasitic pathogens which contaminate foods. Alternatively, tourists are being affected abroad and possibly transmitting the pathogen to others at home. Thus, an increasing number of food-related illnesses are international in scope. In this review parasitic contamination of foods of animal origin, particularly meat and fish, will be discussed together with potential problems associated with water and unwashed fruits and vegetables.

The effect of vitamin A on epithelial integrity.

Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-beta-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A.

Optimal nutrition: vitamin A and the carotenoids.

There are two major dietary sources of vitamin A: easily absorbed retinyl palmitate in foods of animal origin, and poorly bioavailable carotenoids from plant foods. Plasma retinol is tightly controlled, probably by regulation of retinol-binding protein (RBP) formation in the liver, and only hormonal factors (e.g. oral contraceptives) and infection will alter the homeostasis. Delivery of retinol to the tissues is facilitated by the RBP-retinol complex; however, there is evidence that this mechanism can be bypassed when very high doses of vitamin A are given. Some retinyl ester may be released to tissues from chylomicrons when the latter bind to tissue lipoprotein receptors during their passage from the gut to the liver following a meal. High-dose vitamin A therapy is a means of rapidly improving vitamin A status in persons with sub-optimal vitamin A nutrition but there are dangers of toxic symptoms (e.g. teratogenicity) from excess vitamin A usage. Evidence is presented to suggest that the plasma retinol: RBP may be a guide to optimal vitamin A status, since values less than one frequently occur in less-developed countries and during infection. In contrast to plasma retinol, plasma carotenoids reflect the dietary intake of plant foods. However, absorption is limited by poor bioavailability and a saturable uptake mechanism in competition with other phytochemicals. Recent work on bioavailability suggests that the calculation of plant food vitamin A activity should be re-examined. Illness has little influence on plasma levels except by suppressing appetite. Carotenoids are generally regarded as non-toxic yet intervention studies with beta-carotene in smokers have been associated with increased lung cancer and heart disease. Some carotenoids are important as vitamin A precursors, but the physiological importance of their antioxidant properties is not known and consequently the amount needed for optimal nutrition is uncertain.

Giardia intestinalis is unlikely to be a major cause of the poor growth of rural Gambian infants.

Parasite-specific plasma immunoglobulins have been used to indicate the presence of Giardia intestinalis infection in 60 infants living in a rural area of The Gambia. Infants were studied longitudinally between 2 and 8 mo of age. The median age for first exposure to G. intestinalis was between 3 and 4 mo, and by 8 mo all but 3 infants (95%) showed a positive titer on at least one occasion. Raised Giardia-specific IgM titers were associated with reduced weight gain in the 2 wk preceding a positive titer, but catch-up growth occurred in the following 2 wk. IgM antibody titers were also positively associated with intestinal permeability (lactulose/mannitol ratio), urinary lactose excretion, plasma concentrations of alpha1-antichymotrypsin and total IgM, IgA and IgG immunoglobulins. However, infant growth over the whole 6-mo period (i.e., between 2 and 8 mo of age) was not related to mean Giardia-specific antibody titers, nor the time of first exposure to the parasite. The data suggest that giardiasis in these very young breast-fed children occurs as a mild, acute disease, and its presence could not explain the marked, long-term growth faltering observed in many of the subjects.

Maternal reports of child illness and the biochemical status of the child: the use of morbidity interviews in rural Bangladesh.

In a longitudinal study of child growth and nutritional status in Bangladesh, child morbidity was recorded using health interviews with the mother. The aim of the present study was to establish whether maternal reports of child illness were associated with the biochemical health status of the child. Children aged 2-5 years (n 117) took part in the study and their mothers were interviewed every fortnight by Bangladeshi fieldworkers. Maternal reports of diarrhoea were associated with significantly lower plasma albumin concentrations (P < 0.001), poorer intestinal permeability (P < 0.001), higher plasma immunoglobulin A levels (P < 0.005) and higher alpha-1-antichymotrypsin (ACT) levels (P < 0.05) compared with children reported to be healthy. Children with fever had significantly higher ACT (P < 0.001) and lower albumin (P < 0.05) levels compared with their healthy counterparts. Respiratory infections (RI) were not associated with any significant changes; however, reports of RI with fever were associated with significantly higher levels of ACT than either illness individually (interaction P < 0.05). These highly significant associations between maternal reports of illness and biochemical profiles of child health support the use of health interviews in developing countries.

Impact of health service provision on mothers and infants in a rural village in North West Frontier Province, Pakistan.

OBJECTIVE: The objective of this paper is to examine the impact of the Health Service Research Project of the Pakistan Medical Research Council (PMRC) on mothers and infants in Budhni village, North West Frontier Province (NWFP), Pakistan. METHODS: Information from the PMRC records on the socioeconomic and demographic situation over the last 10 years and anthropometric measurements made on all infants from 1986-96 were collected and analysed. RESULTS: The demographic data showed a number of changes, namely a reduction in birth rate and improvements in perinatal, neonatal, infant and child mortality rates. Literacy in the village was poor (27 and 39% literate in 1986 and 1996, respectively) and female literacy showed no improvement (14%). Improvements in sanitation and in the water supply introduced by the PMRC had limited success, as clean water was subsequently contaminated by unclean hands and utensils, and 50% of the population continued to use open fields for sanitation. In 1986 only 27% of children 0-5 years were vaccinated, but by 1996, 96% of children had completed polio, diphtheria/pertussis/tetanus (DPT) and bacille Calmette-Guérin (BCG) vaccination programmes and 95% of women of child-bearing age were vaccinated against tetanus. Protection against tetanus reduced neonatal deaths and from 1993 onwards there have been no further cases. Anthropometric data for the period 1986-96 for infants (0-24 months) showed that at birth the majority of infants were close to the 50th National Centre for Health Statistics (NCHS) centile for weight and length, and only 5% of birth-weights were less than 2.5 kg. Growth charts showed faltering in length and weight and by 24-months length in both boys and girls was below the 3rd NCHS centile and weights were just above. CONCLUSIONS: Reductions in child mortality have occurred over the period 1986-96. However, the slow progress in adopting hygienic practices, despite health education, and the low literacy rates, particularly in women, may hamper continued improvement.

The possible significance of parallel changes in plasma lutein and retinol in Pakistani infants during the summer season.

Recent evidence suggests that plasma lutein is better correlated than either beta-carotene or lycopene with its respective carotenoid intake and therefore may be a better marker of vegetable intake than either beta-carotene or lycopene. In the study reported in this paper, measurements of plasma carotenes and retinol were made in infants from two villages near Peshawar in the North West Frontier Province, Pakistan, in July and November 1993. The approximate age at the start was 14 months, and 101 boys and ninety girls completed the study. Of the usual plasma carotenes, only lutein was measurable in all samples and was correlated with retinol in both boys (r 0.38, P < 0.0001; r 0.35, P < 0.001) and girls (r 0.21, P = 0.038; r 0.0307, P = 0.003) at the two time points respectively. In addition, the change in lutein was even more strongly correlated with the change in retinol in both boys (r 0.453, P < 0.0001) and girls (r 0.439, P < 0.0001). In August beta-carotene was measurable in approximately 8 % of samples and this increased to 31 % in November but there was no correlation between beta-carotene and retinol at any time. There were negligible amounts of lycopene and beta-cryptoxanthin in plasma at both time points. The mean concentration of plasma retinol in the infants was 0.66 mumol/l at baseline and 59% of the infants had retinol concentrations < 0.7 mumol/l. In addition, there were fifteen infants whose levels were below 0.35 mumol/l suggesting that vitamin A status in the population was marginal. Food intake of the infants was not monitored in the present study but breast feeding continues for up to 2 years in this part of Pakistan and most infants would be weaned onto selected foods eaten by the family. The close correlation between plasma lutein and retinol suggests that the increase in retinol over the summer season may be attributable to an increased availability of green vegetables to the families. The source of lutein to the infants is most likely to be the breast milk since such vegetables are unlikely to be given to infants except to suck as a weaning food. The results may indicate the potential usefulness of plasma lutein as a marker of changes in vegetable intake and changes in vitamin A status in Third World infants and children.

Lactose maldigestion in breast-feeding Gambian infants.

BACKGROUND: The ability of breast-feeding infants to utilize lactose, the major carbohydrate in breast-milk, is dependent on the presence of the enzyme lactase (E.C.3.2.1.108). Lactase is located in the brush border of the small intestine and because of its exposed position it is extremely vulnerable to pathogenic damage. Breast-fed Gambian infants have poor growth associated with intestinal damage beyond 3-4 months. The aim of this study was to assess the ability of Gambian infants aged 2-15 months (N = 113) to digest lactose and to see how this varied with age, intestinal permeability, and growth performance. METHODS: Lactose maldigestion was estimated by monthly measurements of urinary lactose and lactulose following an oral dose of the latter. RESULTS: Both urinary lactose excretion and lactulose maldigestion increased with age (p < 0.0001 ANOVA). Up to 6 months the mean urinary lactose: lactulose excretion ratio was within the quoted normal range (< 0.4). Beyond this age, mean values were hypolactasic. Lactose maldigestion was related to poor growth in both weight and length (r = -0.04, p < 0.0001, after age correction). Although a major part of this relationship was a reflection of the previously reported correlation between intestinal permeability and growth, more than 30% of the association was in addition to the permeability effect. Possible explanations are discussed. CONCLUSIONS: Moderate-to-severe hypolactasia does occur in breast-fed Gambian infants and is related to poorer-than-expected growth. However, this does not mean that breast milk intake should be reduced as the nutritional and immunological benefits of breast milk continue to outweigh any disadvantages.

Effect of improved vitamin A status on response to iron supplementation in Pakistani infants.

We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 micrograms/L), and the acute-phase protein alpha 1-antichymotrypsin (ACT; 0.06 g/L). In both the placebo and iron-supplemented groups there were increases in plasma retinol, lutein, alpha-tocopherol, immunoglobulin A, and immunoglobulin G. The improvement in vitamin A status could only have been from a seasonal increase in dietary sources of vitamin A, eg, breast milk and early weaning foods, and there were no obvious effects on iron utilization (hemoglobin concentrations). However, in the infants receiving iron, those whose retinol concentrations increased also showed reductions in ACT, ferritin, immunoglobulin A, and immunoglobulin M. Vitamin A is well known for its antiinfective properties and we suggest that these observations illustrate the importance of even small increases in dietary vitamin A or differences in vitamin A status in reducing the potentially toxic effects of iron supplements in persons in developing countries. These conclusions should now be confirmed with an intervention study to show that the benefits of vitamin A on iron status are due to reduced levels of infection.

The impact of gastrointestinal parasites on protein-energy malnutrition in man.

There is no doubt that at high intensity of infection, intestinal parasites can cause severe illness and the death of their hosts. Even with the high prevalence of these infections, however, such severe cases are rare and the norm is for low to moderate numbers of parasites which cause few if any overt symptoms. Nevertheless, it has been argued that by causing subtle reductions in appetite, absorption, digestion and acute-phase status and increasing intestinal nutrient losses, these low-level but long-term infections could be responsible for the persistent, poor nutritional status of so many children in Third World communities. Although geographically, high parasite prevalence occurs in conjunction with high levels of protein-energy malnutrition, attempts to establish a cause and effect relationship have had very limited success with many investigators being unable to demonstrate any detrimental consequence of infection. The unimpressive results might be explained to some extent by the unusual features of helminth infections such as rapid reinfection, the overdisperse distribution pattern and the uncertainty of a host inflammatory response, but they also suggest that A. lumbricoides (on which most studies have concentrated) may be of little nutritional importance. It seems likely that the more invasive parasites, e.g. the hookworms, S. stercoralis, T. trichiura and perhaps G. lamblia may have a greater impact and clearly more studies are required here. Safe, cheap and effective anthelmintics are now available and, on the grounds of disease prevention, there is a case for their nationwide use. However, from the available evidence, it would be unwise to expect that such programmes would make a significant impact on the nutritional status of children in Third World communities.

A trial of zinc supplementation in young rural Gambian children.

The present study tested the hypothesis that inadequate Zn intake might be responsible for failure to thrive and impaired catch-up growth in young rural Gambian children, and that Zn supplements might be beneficial. Gambian children might be deprived of Zn because of its poor availability from their predominantly plant-based diet. Rural Gambian children (110; fifty boys, sixty girls) aged between 0.57 and 2.30 years were divided into two matched groups, one to receive 70 mg Zn twice weekly for 1.25 years, and the other a placebo. Growth and mid-upper-arm circumference were measured at weekly intervals throughout the study and illnesses were monitored. Capillary blood and urine samples were collected at 0, 2 and 8 weeks. Body weights and arm circumferences showed a linear increase, plus a seasonal effect (rainy season faltering). For body weight there was no significant overall effect of the supplement. For arm circumference, a very small (2%) but significant (P < 0.01) difference favoured the supplemented group. Plasma thymulin was much lower at the first clinic than at the second and third clinics, and in vitro Zn stimulation was greater at the first clinic. There was, however, no effect of Zn in vivo. Likewise, Zn did not significantly benefit T-cell numbers or ratios, secretory IgA in urine, circulating hormone levels or biochemical indices of Zn status. One index of intestinal permeability, i.e. lactulose: creatinine, was improved (P < 0.02) by the supplement, but the lactulose: mannitol value was not; this requires further investigation. Dietary Zn deficiency is, thus, unlikely to be of major overall importance for rural Gambian children's ability to thrive, and blanket Zn supplementation is not justified. There may, however, be vulnerable sub-groups who would benefit from Zn supplements.

Parasitic infection of the gut and protein-losing enteropathy.

Parasitic infection of the gut is highly prevalent in developing countries and contributes to the severe malnutrition associated with persistent diarrhoea in children. Using random faecal alpha 1-antitrypsin measurements as an index of protein-losing enteropathy, we examined children with and without parasitic infection of the gut. Seventeen percent of children with persistent diarrhoea had evidence of protein-losing enteropathy. This was found to be associated with hypoalbuminaemia in children infected with Strongyloides stercoralis. Only a minority (2 of 17) of children infected with Giardia lamblia had raised faecal alpha 1-antitrypsin excretion and this was not associated with hypoalbuminaemia. This study emphasises the need for rapid diagnosis and treatment of Strongyloides infection in children with persistent diarrhoea and severe nutrition.