Gambian Infants Research Articles

Predominant Influence of Environmental Determinants on the Persistence and Avidity Maturation of Antibody Responses to Vaccines in Infants

Immune responses are complex traits influenced by genetic and environmental factors. We previously reported that genetic factors control early antibody responses to vaccines in Gambian infants. For the present study, we evaluated the determinants of the memory phase of immunoglobulin G (IgG) responses. Antibody responses to tetanus toxoid (TT), measles vaccines, and environmental antigens (total IgG levels) were measured in 210 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variations in response. In contrast to antibody responses measured in infants at age 5 months, 1 month after immunization, no significant contribution of genetic factors to anti-TT antibody and total IgG levels was detected at age 12 months. Genetic factors controlled measles antibody responses in 12-month-old infants, which indicates that the increasing influence of environmental determinants on anti-TT responses was not related to the older age of the children but, rather, to the time elapsed since immunization. Environmental factors also predominantly controlled affinity maturation and the production of high-avidity antibodies to TT. Genetic determinants control the early phase of the vaccine antibody response in Gambian infants, whereas environmental determinants predominantly influence antibody persistence and avidity maturation.

Randomized, placebo-controlled, calcium supplementation study in pregnant Gambian women: effects on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion in the first year of life

Growth and bone mineral accretion in Gambian infants are poorer than those in Western populations. The calcium intake of Gambian women is low, typically 300-400 mg Ca/d, and they have low breast-milk calcium concentrations, which result in low calcium intakes for their breastfed infants. A low maternal calcium supply in pregnancy may limit fetal mineral accretion and breast-milk calcium concentrations and thereby affect infant growth and bone mineral accretion. We investigated the effects of calcium supplementation in Gambian women during pregnancy on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion. A randomized, double-blind, placebo-controlled supplementation study was conducted in 125 Gambian women who received 1500 mg Ca/d (as calcium carbonate) or placebo from 20 wk of gestation until delivery. Infant birth weight and gestational age were recorded. Breast milk was collected, and infant anthropometric and bone measurements were performed at 2, 13, and 52 wk after delivery. Infant bone mineral status was assessed by using single-photon absorptiometry of the radius and whole-body dual-energy X-ray absorptiometry. Compliance with the supplement was high. No significant differences were detected between the groups in breast-milk calcium concentration, infant birth weight, or growth or bone mineral status during the first year of life. A slower rate of increase in infant whole-body bone mineral content and bone area was found in the supplement group than in the placebo group (group x time interaction: P = 0.03 and 0.02, respectively). Calcium supplementation of pregnant Gambian women had no significant benefit for breast-milk calcium concentrations or infant birth weight, growth, or bone mineral status in the first year of life.

Treatment and prevention strategies to combat pediatric pneumococcal meningitis

Pneumococcal meningitis is a severe, life-threatening infection of the nervous system affecting infants, children and adults alike. The incidence of pneumococcal meningitis in infants and children less than 2 years of age in Europe is approximately 10 out of 100,000 per year, rising to approximately 148 out of 100,000 per year in Gambian infants. The use of highly sensitive tests such as PCR may increase the likelihood of detecting the infection by 20% or more. Epidemics of serotype 1 pneumococcal meningitis in northern Ghana, have had many of the characteristics of meningococcal meningitis epidemics. Neurologic sequelae may occur in 28–63% of cases, and serotype 3 is associated with a 2.54 relative risk of death. The pathogenic process can be divided into invasion, inflammatory pathways, bacterial toxicity and damage; pneumolysin being particularly associated with apoptosis. In the future, neuroprotection may be achieved, targeting this process at all these levels. Therapeutic guidelines have been published by the Infectious Diseases Society of America. Standard empiric therapy, in those aged greater than or equal to 1 month, is a third-generation cephalosporin plus vancomycin. There is insufficient evidence relating to the use or otherwise of corticosteroids in pneumococcal meningitis to make a firm recommendation. The advent of a pneumococcal conjugate vaccine is the most powerful tool available for the prevention of pneumococcal meningitis in all parts of the world.

Improved thymic function in exclusively breastfed infants is associated with higher interleukin 7 concentrations in their mothers' breast milk

In rural Gambians, the season of birth strongly predicts adult mortality. Those born during the harvest season have longer life spans than do those born during the hungry season, and the deaths associated with infectious diseases suggest permanent early-life influences on immunity. Thymic measurements showed significantly smaller thymuses in infants born during the hungry season than in those born during the harvest season. The differences were greatest at 8 wk of age, a time when all infants were exclusively breastfed, which suggests the involvement of breast milk factors. This study tested whether thymic size differences reflect thymic output and ascertained whether thymic output is associated with breast milk interleukin 7 (IL-7) concentrations. We studied thymic size and output in a prospective cohort of 138 Gambian infants born in either the hungry or the harvest season by measuring signal-joint T cell receptor-rearrangement excision circles (sjTRECs) at birth and at 8 wk of age. IL-7 concentrations in breast milk were measured by using an enzyme-linked immunosorbent assay. By age 8 wk, those born in the hungry season had significantly lower sjTREC counts than did those born in the harvest season (0.97 and 2.12 sjTRECs/100 T cells, respectively; P = 0.006). At 1 wk postpartum, the breast milk of mothers of infants born in the hungry season had significantly lower IL-7 than did that of mothers of infants born in the harvest season (79 and 100 pg/mL, respectively; P = 0.02). The findings were similar at 8 wk postpartum. These data show a plausible pathway linking external seasonal insults to mothers with thymic development in their infants, which suggests possible implications for long-term programming of immunity.

Specific immunoglobulin A antibodies in maternal milk and delayed Helicobacter pylori colonization in Gambian infants.

Immunoglobulin A (IgA) in maternal milk may protect Gambian infants from early Helicobacter pylori colonization. This study sought evidence that this protection could be due to specific IgA antibodies. Sixty-five infants were screened from 12 weeks of age with [13C]-urea breath tests. Antibodies in maternal milk were measured to determine total IgA content and to detect specific IgA antibodies against crude whole-cell and recombinant H. pylori urease antigen preparations. Ten children (15%) had no evidence of early H. pylori colonization, 10 (15%) had early H. pylori colonization, and 43 (66%) had mixed results. Levels of maternal circulating specific immunoglobulin G, total milk IgA, and IgA directed against crude whole-cell H. pylori antigen preparation were not significantly associated with the rate of infant H. pylori colonization. However, mothers of infants with no evidence of early colonization produced significantly higher levels of anti-recombinant urease IgA antibodies in milk than did control mothers, particularly at 8, 16, and 20 weeks postpartum (P<.01). These observations support the hypothesis that antibodies in mother's milk directed against H. pylori urease can protect against colonization in human infancy.

Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability.

Investigate whether fecal neopterin concentration (a potential marker of gut inflammation) in Gambian children with enteropathy was associated with growth failure. Secondary outcome measures tested the associations between Giardia lamblia infestation, fecal neopterin and lactulose mannitol absorption ratio(L:M), a measure of intestinal permeability. Seventy-two children had height and weight measured every 6 to 8 weeks until 15 months of age in a rural Gambian village. L:M ratio, a measure of small intestinal permeability and fecal neopterin were measured at these times. Stool was examined by immunofluorescence and light microscope for Giardia cysts. Long-term height and weight gains were negatively associated with mean subject fecal neopterin concentration (r = -0.29 and -0.36, respectively; P < 0.001). There was no correlation between fecal neopterin and intestinal permeability or history of diarrhea. Of 72 children studied, 19 had Giardia cysts in stool and 38 had negative stool examinations. Infected children had a mean of 0.7 days of diarrhea/week (95% confidence interval [CI], 0.31-1.03) versus 0.8 days/week (95% CI, 0.71-0.85) in uninfected children. No difference in growth was detected between those with positive or negative fecal smears. Mean L:M ratio was the same in both groups (0.31; 95% CI, 0.26-0.34). Consistent with the theory that intestinal inflammation in tropical infants may impair growth, fecal neopterin concentrations were inversely associated with growth. Factors other than Giardia are causing enteropathy and growth failure in Gambian infants.

Intestinal Inflammation Measured by Fecal Neopterin in Gambian Children With Enteropathy: Association With Growth Failure, Giardia lamblia, and Intestinal Permeability

ABSTRACTObjectives:Investigate whether fecal neopterin concentration (a potential marker of gut inflammation) in Gambian children with enteropathy was associated with growth failure. Secondary outcome measures tested the associations between Giardia lamblia infestation, fecal neopterin and lactulose mannitol absorption ratio(L:M), a measure of intestinal permeability.Methods:Seventy‐two children had height and weight measured every 6 to 8 weeks until 15 months of age in a rural Gambian village. L:M ratio, a measure of small intestinal permeability and fecal neopterin were measured at these times. Stool was examined by immunoflorescence and light microscope for Giardia cysts.Results:Long‐term height and weight gains were negatively associated with mean subject fecal neopterin concentration (r = −0.29 and −0.36, respectively; P &lt; 0.001). There was no correlation between fecal neopterin and intestinal permeability or history of diarrhea. Of 72 children studied, 19 had Giardia cysts in stool and 38 had negative stool examinations. Infected children had a mean of 0.7 days of diarrhea/week (95% confidence interval [CI], 0.31–1.03) versus 0.8 days/week (95% CI, 0.71–0.85) in uninfected children. No difference in growth was detected between those with positive or negative fecal smears. Mean L:M ratio was the same in both groups (0.31; 95% CI, 0.26–0.34).Conclusions:Consistent with the theory that intestinal inflammation in tropical infants may impair growth, fecal neopterin concentrations were inversely associated with growth. Factors other than Giardia are causing enteropathy and growth failure in Gambian infants.

Birth season and environmental influences on patterns of thymic growth in rural Gambian infants

In rural Gambia, birth season predicts infection-related adult mortality. Seasonal factors in early life may programme the immune system, possibly via an effect on thymic development. This study tested whether thymus size in rural Gambian infants is affected by birth season, defined as January-June (harvest, few infections) versus July-December (hungry, high infectious load). Thymic volume (thymic index) was assessed sonographically at 1, 8, 24 and 52 wk in 138 singleton infants born over 14 consecutive months. Growth and morbidity were regularly assessed. Mean thymic index increased from 19.9 at 1 wk to 30.9 at 8 wk and 35.7 at 24 wk, then fell to 32.0 at 52 wk. Thymic index was associated with each preceding thymic index up to 24 wk. This tracking persisted after correcting for infant weight and month of measurement (p < 0.01). Thymic index at 1 wk was marginally but non-significantly lower in hungry season births (p = 0.06). Thymic index was lower in hungry season measurements; this effect persisted after adjusting for current weight and infection markers, and was strongest at 8 wk (p = 0.001). These results describe a pattern of thymic growth followed by diminution in size. An infant's thymic index tracks despite changes in body weight and season. Thymic index was lower in the hungry season. This appears not to be explained by infection or nutritional status. A possible influence of trophic factors in breast milk merits investigation.

The size of the thymus: an important immunological diagnostic tool?

The report on the influence of seasonal factors on thymic size in early life describes a pattern of ultrasonographically measured thymic growth in Gambian infants including the finding of a smaller thymus in the hungry season. These factors raise a number of important questions: Is the size of the thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? Studies using the size of the thymus as an immunological diagnostic tool should be encouraged.

Birth season and environmental influences on patterns of thymic growth in rural Gambian infants

Aim: In rural Gambia, birth season predicts infection-related adult mortality. Seasonal factors in early life may programme the immune system, possibly via an effect on thymic development. This study tested whether thymus size in rural Gambian infants is affected by birth season, defined as January-June (harvest, few infections) versus July-December (hungry, high infectious load). Methods: Thymic volume (thymic index) was assessed sonographically at 1, 8, 24 and 52 wk in 138 singleton infants born over 14 consecutive months. Growth and morbidity were regularly assessed. Results: Mean thymic index increased from 19.9 at 1 wk to 30.9 at 8 wk and 35.7 at 24 wk, then fell to 32.0 at 52 wk. Thymic index was associated with each preceding thymic index up to 24 wk. This tracking persisted after correcting for infant weight and month of measurement (p < 0.01). Thymic index at 1 wk was marginally but non-significantly lower in hungry season births (p= 0.06). Thymic index was lower in hungry season measurements; this effect persisted after adjusting for current weight and infection markers, and was strongest at 8 wk (p= 0.001). Conclusion: These results describe a pattern of thymic growth followed by diminution in size. An infant's thymic index tracks despite changes in body weight and season. Thymic index was lower in the hungry season. This appears not to be explained by infection or nutritional status. A possible influence of trophic factors in breast milk merits investigation.

Growth Faltering in Rural Gambian Infants Is Associated with Impaired Small Intestinal Barrier Function, Leading to Endotoxemia and Systemic Inflammation

Growth faltering of rural Gambian infants is associated with a chronic inflammatory enteropathy of the mucosa of the small intestine that may impair both digestive/absorptive and barrier functions. The aim of this study was to determine whether the enteropathy was associated with a compromised barrier function that allowed translocation of antigenic macromolecules from the gut lumen into the body, with subsequent systemic immunostimulation, resulting in growth retardation. Rural Gambian infants were studied longitudinally at regular intervals between 8 and 64 wk of age. On each study day, each child was medically examined, anthropometric measurements were made, a blood sample was taken and an intestinal permeability test performed. Evidence of chronic immunostimulation was provided by abnormally elevated white blood cell, lymphocyte and platelet counts, and frequently raised plasma concentration of C-reactive protein. Intestinal permeability was abnormal and associated with impaired growth (r = -0.41, P < 0.001). Plasma concentrations of endotoxin and immunoglobulin (Ig)G-endotoxin core antibody were also elevated and related to both growth (r = -0.30, P < 0.02; r = -0.64, P < 0.0001, respectively) and measures of mucosal enteropathy. Plasma IgG, IgA and IgM levels increased rapidly with age toward adult concentrations. Raised values were related to poor growth but also to measures of mucosal enteropathy and the endotoxin antibody titer. The interrelationships among these variables and growth suggested that they were all part of the same growth-retarding mechanism. These data are consistent with the hypothesis of translocation of immunogenic lumenal macromolecules across a compromised gut mucosa, leading to stimulation of systemic immune/inflammatory processes and subsequent growth impairment.

Age-related association of small intestinal mucosal enteropathy with nutritional status in rural Gambian children.

Small bowel enteropathy (assessed by the lactulose (L) : mannitol (M) permeability test) is a major factor in infant growth faltering and malnutrition in The Gambia. However, little is known about its persistence and nutritional effect beyond 2 years of age. This was addressed by two cross-sectional studies of intestinal permeability and nutritional status in 162 residents, aged 2-60 years, living in three villages in rural Gambia. L:M ratio was found to be highest in the youngest children and although there was a significant improvement with age (P<0.0001), values were always greater than the range found in UK counterparts. M recovery (mean value 5.68 (se 0.12) %) was at all times between one-third and one-half of expected UK values and showed no improvement with age. Gut barrier function, assessed by L uptake, improved with age (P<0.001) and fell within the UK normal range beyond age 10 years. Both the L:M permeability ratio and L recovery were significantly associated with height-for-age z-scores and -0.22 respectively, P<0.001), a relationship that persisted throughout childhood and into adulthood. Change in height-for-age z-score between the two visits was also related to the L:M ratio P=0.018). The close within-subject correlation of permeability variabilities between the two visits suggests a long-term persistence of enteropathy within individuals. It appears that the small bowel enteropathy previously described in Gambian infants persists through to adulthood. Although the lesion improves with age, the relationship between attained height and L:M permeability raises the possibility that enteropathy may continue to limit growth throughout childhood and puberty.

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.

Etiology of serious infections in young Gambian infants.

Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.

Antigenuria in gambian infants following immunization with a Haemophilus influenzae type b polyribosylribitol phosphate-tetanus toxoid protein conjugate (PRP-T) vaccine

During a Haemophilus influenzae type b (Hib)–conjugate vaccine trial, the prevalence and duration of antigenuria after vaccination was studied in 102 Gambian infants aged 51 to 175 days. Urine samples were collected at 0, 1, 3, 7, 14, 21 and 28 days postvaccination and tested for Hib antigen by latex agglutination using Biomérieux and Directigen reagent kits. Biomérieux positive reactions were found in 6 of 247 (2.4%) samples from vaccinated children and in 8 of 199 (4.0%) from nonvaccinated children (χ 2 = 0.47; 1 df; p = 0.5). In contrast, Directigen positive reactions were obtained with 86/242 samples (35.5%) from vaccinated children and from 28/190 (14.7%) from non-vaccinated children (χ 2 = 22.7; 1 df; p <0.0001). The highest rate of antigenuria was detected in samples collected on Day 7 after vaccination when 24 of 30 (80%) were positive. Antigenuria following vaccination was frequent and may complicate the use of this test as a means of diagnosing invasive Hib disease in vaccinated children.

The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us about the burden of Haemophilus influenzae type b disease?

The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world. The most frequent manifestations of Hib disease are pneumonia and meningitis. In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era. The burden of Hib pneumonia is more difficult to define. Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia. A Gambian study found Hib to be responsible for 7% of cases. However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia. The same trial demonstrated a mild herd effect, so this figure may be an underestimate. The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae. Vaccine trials may reveal the true burden of that pathogen also.

Specific anti-H. pyloriurease IgA in human Breastmilk and delayedH. pyloricolonisation in Gambian infants.

124 H. pylori, one of the commonest human bacterial infections, is usually acquired in childhood. We sought evidence for a role of specific matemal milk IgA against H. pylori colonisation in 65 breast fed Gambian infants, in whom H. pylori was diagnosed using monthly13 C UBTs across the first year of life. IgA against crude whole cellH. pylori antigen and recombinant H. pylori urease were measured by immunoassay. 85% of infants developed one or more positive UBTs during their first year of life. For infants born in the first 6 months (n=32), following problems with the village water supply, the median age of colonisation (first positive UBT) was 8 weeks. Following this period it rose to 28 weeks. Mean levels (o.d. ratio) of milk IgA directed against rUrease were lower (p<0.001) in the milk from mothers of infants born in the first 4 months of the study (0.091, 95% Cl 0.71-0.111) than in mothers of infants born thereafter (0.177, 95% Cl 0.163-0.191). Mothers of infants who remained free from colonisation throughout the first year produced significantly higher median levels of anti-rUrease IgA than the other mothers (0.183 vs. 0.135, p=0.027). There was no association found between total IgA or IgA against crude whole cell anti-H. pylori antigen and infants UBT results. The most striking differences in antibody levels occurred during the first 3 months of life, when the milk of mothers of non-colonised children had significantly higher levels of anti-rUrease IgA at 4, 8, and 12 weeks than that of mothers of children who developed early H. pylori colonisation (p<0.005, p<0.005, p<0.25 respectively). The associations, and the temporal relationships between them, provide the first good evidence to support the hypothesis that human breastmilk antibodies directed against H. pylori urease can protect against colonisation in infancy.

Helicobacter pylori infection, gastric acid secretion, and infant growth.

Helicobacter pylori infection is very common in Gambian infants and children, who are also at risk of chronic diarrhoea and undernutrition. Acute H. pylori infection is associated with depressed gastric acid secretion, and loss of the gastric acid barrier may predispose to enteric infections. In a prospective study a noninvasive test of gastric acid output (measurement of change in urine acid output before and after a feed) was performed on a population of Gambian infants at high risk of H. pylori infection. The 13C urea breath tests was used to measure the prevalence of H. pylori infection and growth was measured by serial anthropometry. In 101 infants aged 3 to 12 months, there was a significant relation between H. pylori infection and depressed urine acid output in those aged 6 months, during weaning when growth failure and malnutrition begin. Those infants with sustained H. pylori infection grew less well than those without. We speculate that H. pylori, acquired in infancy, could be a "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.

An efficacy trial of the malaria vaccine SPf66 in Gambian infants—second year of follow-up

In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI −20%, 30%] and 2% [95% CI −26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.