PubMed Health⌕ Search

Biomedical subjects

Sophie E Moore

Publications and source records attributed to Sophie E Moore.

11 recordsLinked to original sources
PubMed2006

Early immunological development and mortality from infectious disease in later life.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating 'hungry' season, suggesting that immune function may be compromised by events early in life. The current programme of research focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research.

Adult↗
PubMed2006

Effect of month of vaccine administration on antibody responses in The Gambia and Pakistan.

OBJECTIVE: To explore the relationship between calendar month of administration and antibody (Ab) response to vaccination in subjects from The Gambia and Pakistan, two countries with distinct patterns of seasonality. METHODS: Three cohorts were investigated: Responses to rabies and pneumococcal vaccine were assessed in 472 children (mean age 8 years, males 53%) from rural Gambia. Responses to tetanus, diphtheria and hepatitis B (HBsAg) were investigated in 138 infants also from The Gambia (birth to 52 weeks of age, males 54%). Responses to rabies and Vi typhoid vaccines were assessed in 257 adults from Lahore, Pakistan (mean age 29.4 years, males 57%). RESULTS: In Gambian children, significant associations were observed between month of vaccination and Ab response for the pneumococcal and rabies vaccines. As no consistent pattern by month was observed between the responses, it is assumed that different immunomodulatory stimuli or mechanisms were involved. In Pakistani adults, a significant pattern by month of vaccination was observed with both rabies and typhoid vaccine. No monthly influences were observed in the infant study to the tetanus, diphtheria or the HbsAg vaccines. CONCLUSIONS: Antibody responses to certain specific vaccines are influenced by month of administration. Further research is required to elucidate the precise mechanisms explaining these observations, but a co-stimulatory effect of seasonally variable environmental antigens is a likely cause. Future studies of Ab response to vaccination in countries with a seasonally dependent environment should consider month of vaccination when interpreting study findings.

Adult↗
PubMed2006

Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults.

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.

Adult↗
PubMed2005

Insights from the developing world: thrifty genotypes and thrifty phenotypes.

Few researchers would dispute that the pandemic of obesity is caused by a profound mismatch between humanity's present environmental circumstances and those that have moulded evolutionary selection. This concept was first articulated when gestational diabetes was described as being the result of a 'thrifty genotype rendered detrimental by progress'. More recently, this hypothesis has been extended to the concept of a 'thrifty phenotype' to describe the metabolic adaptations adopted as a survival strategy by a malnourished fetus; changes that may also be inappropriate to deal with a later life of affluence. Both the thrifty genotype and the thrifty phenotype hypotheses would predict that populations in some areas of the developing world would be at greater risk of obesity and its co-morbidities; a proposition to be explored in the present paper. To date thrifty genes remain little more than a nebulous concept propagated by the intuitive logic that man has been selected to survive episodic famine and seasonal hungry periods. Under such conditions those individuals who could lay down extra energy stores and use them most efficiently would have a survival advantage. The search for candidate thrifty genes needs to cover every aspect of human energy balance from food-seeking behaviour to the coupling efficiency of oxidative phosphorylation. The present paper will describe examples of attempts to find thrifty genes in three selected candidate areas: maternally-transmitted mitochondrial genes; the uncoupling proteins; apoE4, whose geographical distribution has been linked to a possible thrifty role in lipoprotein and cholesterol metabolism.

Adaptation, Physiological↗
PubMed2004

Birth weight predicts response to vaccination in adults born in an urban slum in Lahore, Pakistan.

BACKGROUND: Substantial evidence exists linking small size at birth to later-life susceptibility to chronic disease. Evidence is also emerging that some components of immune function may be programmed in early life. However, this evidence is limited and requires confirmation. OBJECTIVE: We investigated the association between size at birth and response to vaccination in a cohort of 257 adults (mean age: 29.4 y; 146 men) born in an urban slum in Lahore, Pakistan, during 1964-1978. DESIGN: A single dose of Vi polysaccharide vaccine for Salmonella typhi and 2 doses of rabies vaccine were given to each subject. Antibody titers were measured in prevaccination serum samples (Vi) and in postvaccination samples (Vi and rabies). RESULTS: The mean birth weight of the subjects was 3.24 kg; 14% of the subjects had low birth weights (<2.5 kg). Vaccine responses were not consistently associated with contemporary variables (month of study, sex, current age, or indicators of wealth). Response to typhoid vaccination was positively related to birth weight (anti-Vi immunoglobulin G: r = 0.138, P = 0.031; anti-Vi immunoglobulin M: r = 0.197, P = 0.034). Response to the rabies vaccine was not significantly associated with birth weight. CONCLUSIONS: These findings add to a growing body of evidence suggesting that components of the immune system may be permanently programmed by events in early life. The contrasting effects on typhoid and rabies responses suggest that antibody generation to polysaccharide antigens, which have greater B cell involvement, is compromised by fetal growth retardation.

Adult↗
PubMed2004

Comparative analysis of patterns of survival by season of birth in rural Bangladeshi and Gambian populations.

BACKGROUND: Analysis of data from rural Gambia has previously shown that being born during the annual hungry season strongly influences susceptibility to mortality from infectious disease in young adulthood, possibly through an influence on immune function. In rural Bangladesh pregnancies are exposed to similar seasonality. The current paper uses data from a large demographic survey in the Matlab region of Bangladesh to retest the Gambian-derived hypothesis that early life exposures correlated with season of birth predict later patterns of mortality. METHODS: Since 1966, a continuous demographic surveillance system has been in operation in the rural Matlab region of Bangladesh. The current analysis is based on 172 228 births and 24 697 deaths between 1974 and 2000. Season of birth was defined as 'harvest' (January-June) and 'hungry' (July-December), based on monthly variations in rates of conception and neonatal mortality within the same dataset. RESULTS: Birth during the hungry season resulted in excess mortality during the first year of life. However, for adult mortality (deaths >15 years), there was no excess in individuals born during the annual hungry season: ratio of hazard July-December versus January-June = 1.12; 95% CI: 0.87, 1.45. CONCLUSIONS: The current study found no excess mortality in young adults born during the 'hungry' season in rural Bangladesh. This differing pattern in survival when compared with The Gambia may be a consequence of the greatly reduced incidence of young adult deaths in Bangladesh (0.1%) compared with The Gambia (3%). Under such conditions possible differences in immune function may not be detectable with early adult death as the outcome. However, it also remains possible that our Gambian observation could be a highly discrete phenomenon localized in either time or place, and as such, will not be replicated in other populations.

Adolescent↗
PubMed2004

Fifty-year mortality trends in three rural African villages.

OBJECTIVE: To determine differential improvements in mortality rates according to age, and to discuss differences in neonatal and post-neonatal mortality rates, using longitudinal data from the past 50 years in three rural Gambian villages. METHODS: All villagers whose date of birth was recorded were followed up until death or October 1997. A Lexis expansion was performed to categorize age: early neonatal, late neonatal, infant, 1-4 years, 5-14 years and 15 or more years. Calendar time was divided into three periods -- prior to 1975, 1975-1984 and after 1985, representing different levels of clinical care. Cox regression and likelihood-ratio test were used to model the hazards ratios. RESULTS: There were 3981 subjects included in the analysis with a total of 59 002 person-years follow-up. There was a dramatic decrease in neonatal (44 to 15), infant (162 to 36) and under-five mortality rates (397-66 per 1000) from pre-1975 to the present. The disproportionate decrease in the mortality rates means that neonatal deaths accounted for a greater percentage of post-natal deaths in later years. There was a marked seasonality in mortality rates with significantly more deaths in the 'hungry' season prior to 1975 (odds = 1.87; 95% CI = 1.62-2.17) and from 1975 to 1984 (odds = 1.84; 95% CI = 1.34-2.53). This seasonality of death has diminished in recent years (odds = 1.23; 95% CI = 0.85-1.76). CONCLUSION: Our analysis indicates a dramatic reduction in mortality rates and an attenuation in the seasonality of death. It is likely that the efficient implementation of basic currently available health measures was one of the key elements in achieving such a major reduction in mortality.

Adolescent↗
PubMed2003

Modification of immune function through exposure to dietary aflatoxin in Gambian children.

Aflatoxins are immunotoxins that frequently contaminate staple foods in The Gambia and other parts of sub-Saharan Africa, resulting in high exposure throughout life. Impaired infant immune system development may be a key predictor of mortality from infectious disease. In this study we aimed to determine the effect of dietary aflatoxin exposure on a number of immune parameters in Gambian children. A cohort of 472 Gambian children 6-9 years of age was recruited. Serum aflatoxin-albumin (AF-alb) adducts were analyzed to provide a measure of exposure. Immune parameters included secretory IgA (sIgA) in saliva, cell-mediated immunity (CMI), determined using the CMI multitest where test antigens are applied to the skin, and antibody responses to both rabies and pneumococcal polysaccharide vaccines. Birth weight, current anthropometry, and micronutrient status were also recorded. AF-alb adducts were detected in 93% of the children (geometric mean level 22.3 pg/mg; range 5-456 pg/mg). AF-alb level was strongly influenced by month of sampling. In a multivariable analysis, sIgA was markedly lower in children with detectable AF-alb compared with those with nondetectable levels [50.4 micro g/mg protein (95% confidence interval [CI] 48.0-52.8) and 70.2 micro g/mg protein (95% CI 61.1-79.2), respectively; p < 0.0001]. Antibody response to one of four pneumococcal serotypes, but not rabies vaccine, was weakly associated with higher levels of AF-alb. There was no association between CMI responses to test antigens and AF-alb. These data confirm that children in rural Gambia are frequently exposed to high levels of aflatoxin. The study provides evidence that sIgA in saliva may be reduced because of dietary levels of aflatoxin exposure. Given the high burden of infection-related mortality in West Africa, further investigation of the immune effects of aflatoxin exposure in children is merited.

Aflatoxins↗