Biomedical subjects

L S Stephenson

Publications and source records attributed to L S Stephenson.

At least 19 recordsLinked to original sources

PubMed2001

Optimising the benefits of anthelmintic treatment in children.

Optimal use of anthelmintics in children is of major public health importance because the parasites involved probably infect over 2 billion persons, and most are especially common and debilitating in children. Well targeted drug delivery, particularly via community chemotherapy, can substantially decrease aggregate morbidity and mortality and also improve growth rates, physical fitness and activity, cognitive and school performance, and social well-being. The drugs discussed here include the benzimidazoles (albendazole, levamisole and mebendazole), pyrantel, praziquantel, oxamniquine, ivermectin, diethylcarbamazine and some traditional medicines. The parasitic infections discussed are hookworm, ascariasis, trichuriasis, strongyloidiasis, schistosomiasis and lymphatic filariasis; onchocerciasis and loiasis are also mentioned briefly. Dosage regimens and effectiveness, including combination treatment, are discussed. Mechanisms by which parasites may cause or aggravate malnutrition and retard development are shown, along with examples of nutritional and functional improvement at various ages due to antiparasitic treatment. Improvement in appetite is likely to be the single most important mechanism through which a variety of physiological improvements occur. We recommend community treatment of girls and women of childbearing age in areas with widespread hookworm and anaemia, because effective treatment can reduce the incidence of low birthweight, mortality in infancy and pregnancy, and stunted growth and morbidity in children and adults. Treatment of moderate-to-severe anaemia improves appetite, growth and cognitive and school performance in children, and also improves work and social capacity and productivity in children and adults. Since treatment for helminth infections may also decrease both the probability of contracting HIV infection and the rate of viral replication in those infected with both types of organisms, large-scale treatment and control of helminths and treatment of individual cases when diagnosed are now truly urgent.

Anthelmintics↗

PubMed2000

Global malnutrition.

The four most important forms of malnutrition worldwide (protein-energy malnutrition, iron deficiency and anaemias (IDA), vitamin A deficiency (VAD), and iodine deficiency disorders (IDD)) are examined below in terms of their global and regional prevalences, the age and gender groups most affected, their clinical and public health consequences, and, especially, the recent progress in country and regional quantitation and control. Zinc deficiency, with its accompanying diminished host resistance and increased susceptibility to infections, is also reviewed. WHO estimates that malnutrition (underweight) was associated with over half of all child deaths in developing countries in 1995. The prevalence of stunting in developing countries is expected to decline from 36% in 1995 to 32.5% in 2000; the numbers of children affected (excluding China) are expected to decrease from 196.59 millions to 181.92 millions. Stunting affects 48% of children in South Central Asia, 48% in Eastern Africa, 38% in South Eastern Asia, and 13-24% in Latin America. IDA affects about 43% of women and 34% of men in developing countries and usually is most serious in pregnant women and children, though non-pregnant women, the elderly, and men in hookworm-endemic areas also comprise groups at risk. Clinical VAD affects at least 2.80 million preschool children in over 60 countries, and subclinical VAD is considered a problem for at least 251 millions; school-age children and pregnant women are also affected. Globally about 740 million people are affected by goitre, and over two billions are considered at risk of IDD. However, mandatory salt iodisation in the last decade in many regions has decreased dramatically the percentage of the population at risk. Two recent major advances in understanding the global importance of malnutrition are (1) the data of 53 countries that links protein-energy malnutrition (assessed by underweight) directly to increased child mortality rates, and (2) the outcome in 6 of 8 large vitamin A supplementation trials showing decreases of 20-50% in child mortality.

Adolescent↗

PubMed2000

Malnutrition and parasitic helminth infections.

The Global Burden of Disease caused by the 3 major intestinal nematodes is an estimated 22.1 million disability-adjusted life-years (DALYs) lost for hookworm, 10.5 million for Ascaris lumbricoides, 6.4 million for Trichuris trichiura, and 39.0 million for the three infections combined (as compared with malaria at 35.7 million) (World Bank, 1993; Chan et al. 1994); these figures illustrate why some scarce health care resources must be used for their control. Strongyloides stercoralis is the fourth most important intestinal worm infection; its nutritional implications are discussed, and the fact that its geographic distribution needs further study is emphasized. Mechanisms underlying the malnutrition induced by intestinal helminths are described. Anorexia, which can decrease intake of all nutrients in tropical populations on marginal diets, is likely to be the most important in terms of magnitude and the probable major mechanism by which intestinal nematodes inhibit growth and development. We present a revised and expanded conceptual framework for how parasites cause/aggravate malnutrition and retard development in endemic areas. Specific negative effects that a wide variety of parasites may have on gastrointestinal physiology are presented. The synergism between Trichuris and Campylobacter, intestinal inflammation and growth failure, and new studies showing that hookworm inhibits growth and promotes anaemia in preschool (as well as school-age) children are presented. We conclude by presenting rationales and evidence to justify ensuring the widest possible coverage for preschool-age children and girls and women of childbearing age in intestinal parasite control programmes, in order to prevent morbidity and mortality in general and specifically to help decrease the vicious intergenerational cycle of growth failure (of low-birth-weight/intrauterine growth retardation and stunting) that entraps infants, children and girls and women of reproductive age in developing areas.

Adolescent↗

PubMed2000

The public health significance of Trichuris trichiura.

An estimated 1049 million persons harbour T. trichiura, including 114 million preschool-age children and 233 million school-age children. The prevalence of T. trichiura is high and may reach 95% in children in many parts of the world where protein energy malnutrition and anaemias are also prevalent and access to medical care and educational opportunities is often limited. The Trichuris dysentery syndrome (TDS) associated with heavy T. trichiura, which includes chronic dysentery, rectal prolapse, anaemia, poor growth, and clubbing of the fingers constitutes an important public health problem, as do lighter but still heavy infections, even if not strictly TDS, especially in children. The profound growth stunting in TDS can be reversed by repeated treatment for the infection and, initially, oral iron. However findings from Jamaica strongly suggest that the significant developmental and cognitive deficits seen are unlikely to disappear without increasing the positive psychological stimulation in the child's environment. The severe stunting in TDS now appears likely to be a reaction at least in part to a chronic inflammatory response and concomitant decreases in plasma insulin-like growth factor-1 (IGF-1), increases in tumor necrosis factor-alpha (TNF-alpha) in the lamina propria of the colonic mucosa and peripheral blood (which likely decrease appetite and intake of all nutrients) and a decrease in collagen synthesis. Improvements in cognitive performance have been found after treatment for relatively heavy infections (without chronic dysentery) in school-going children; it is unclear precisely how much T. trichiura interferes with children's ability to access educational opportunities, but treatment of infections whenever possible is obviously sensible. The blood loss that can occur in T. trichiura infection is likely to contribute to anaemia, particularly if the child also harbours hookworm, malaria and/or has a low intake of dietary iron. Community control is important, particularly for the individuals within a population who harbour heavy worm burdens; this means children, with special attention to girls who will experience increased iron requirements and blood loss due to menstruation, pregnancies, and lactation. Mebendazole and albendazole, both of which are on the WHO Essential Drugs List, are very effective against T. trichiura; multiple doses are needed to attain complete parasitological cure in all cases. However the goal of control programmes in endemic areas is morbidity reduction, which follows when intensity of infection is significantly reduced.

Adolescent↗

PubMed1999

Determinants of plasma retinol concentrations of middle-aged women in rural China.

The purpose of this study was to assess the correlates and possible determinants of plasma vitamin A among middle-aged women in rural China. The vitamin A adequacy of the different diets at the five widely varying survey sites was also assessed. Patterns of correlations among dietary and biochemical measurements were strikingly different from previous studies in Western subjects. Plasma beta-carotene was uncorrelated with beta-carotene intake even after adjusting for potential confounders. In counties with low preformed vitamin A intake, plasma retinol correlated with plasma copper (P = 0.007), which in turn was correlated with dietary intake of copper (P = 0.007). In these counties plasma retinol was correlated with plasma beta-carotene (P = 0.001) and was increased 10% in women in the first 2 y of menopause (P = 0.028). Plasma retinol and C-reactive protein levels are inversely correlated (r = -0.15, P < 0.001), indicating that vitamin A status and inflammatory response may be related but the causal direction is unknown. Despite low intake of vitamin A (county averages of 13-78% of recommended daily allowance [RDA]), and particularly of preformed vitamin A, only 3% of these women had plasma retinol levels below 0.7 mumol/L, considered to indicate possible marginal deficiency. Plasma levels of retinol and beta-carotene were more influenced by intrinsic factors such as menopause, lipid status, retinol requirements, and possibly copper status and inflammation than by extrinsic factors such as diet and lifestyle.

Adult↗

PubMed1999

Iron status of middle-aged women in five counties of rural China.

OBJECTIVE: To determine the relationships of dietary iron sources, other dietary factors, and lifestyle to iron status among premenopausal and recently postmenopausal Chinese women with widely varying regional dietary patterns. DESIGN: Cross-sectional. Subjects were interviewed, blood samples were drawn, and dietary intakes were measured by a 3-day dietary survey for subjects in the five survey counties. SETTING: Rural China. SUBJECTS: About 80 randomly selected subjects per county among women aged 32 66 y. MAIN OUTCOME MEASURES: Blood hemoglobin, plasma ferritin, and plasma iron. RESULTS: Total iron intake was relatively high (15-29 mg/d) compared to developed counties. Heme iron intake was negligible in two of the study counties. Overall levels of iron deficiency anemia were relatively low in these generally iron-stressed women. There was no clear statistical relationship between iron intake and physiological iron status. Although several measures of dietary intake (heme iron, dietary calcium, animal protein) were correlated with several measures of iron status before adjusting for survey county, only dietary animal protein was significantly positively correlated with plasma ferritin after adjusting for the possibly confounding factor of the survey county (r= 0.15, P = 0.009). Intakes of potential inhibitors of iron absorption, such as tea, even in very high amounts, were not correlated to iron status. Plasma ferritin was positively correlated with plasma retinol (P = 0.024) and cholesterol (P = 0.007). Systemic inflammatory response, as indicated by high plasma C-reactive protein levels, was shown to be raised in a group of subjects with apparently contradictory high levels of ferritin and low levels of hemoglobin (P = 0.03). CONCLUSIONS: Iron nutriture in these areas of rural China seemed more related to physiological factors such as inflammatory response, menses, plasma vitamin A and cholesterol, than to dietary factors.

Adult↗

PubMed1998

False-positive Trichuris suis egg counts in pigs in relation to coprophagia.

Sixteen non-infected control pigs housed together with 16 pigs infected with Trichuris suis, excreted T. suis eggs in their faeces (range 20-4, 960 eggs per gram faeces (EPG)). When the control pigs were moved to clean pens, their egg counts dropped to zero EPG within five days. A significant correlation was found between T. suis egg counts of infected and control pigs penned together (r = 0.89, P < 0.001). These results suggest that false-positive faecal egg counts may be the result of coprophagia.

Animals↗

PubMed1997

False-positive Ascaris suum egg counts in pigs.

False-positive Ascaris suum egg counts in pig faeces are frequently observed under both experimental and natural conditions. Data from 12 experiments with A. suum infections in pigs were summarized and showed that the percentage of false-positive faecal samples ranged from 4 to 36%. False-positive egg count values varied greatly between pigs and experiments (range 20-1060 eggs per gram faeces). Indoor experiments with pigs housed groupwise in pens generally produced more and higher false-positive egg counts, which may reflect differences in surface area and hence exposure to infective eggs, compared with pasture experiments. The positive predictive value (the number of pigs diagnosed positive by faecal sample that actually harboured worms) was low for indoor experiments (45%) compared with pasture experiments (89%). Differences in design for indoor experiments, such as floor type and use of bedding material, did not influence the positive predictive value (44-47%). A positive correlation was found (r = 0.56, P < 0.05) between faecal egg counts of true-positive and false-positive pigs that were penned together. The results of this survey strongly support previous suggestions that false-positive A. suum egg counts in pigs are the result of coprophagia in indoor experiments and coprophagia/geophagia in pasture experiments. False-positive A. suum egg counts in pig faeces may vary greatly in prevalence and magnitude, and depend in part on management/housing factors.

Animals↗

PubMed1997

Relationships between soil-transmitted helminthiases and growth in urban slum schoolchildren in Ujung Pandang, Indonesia.

This study examined the relationship between intestinal helminthiases and growth in urban slum schoolchildren. Children (n = 330) who received single doses of either pyrantel, albendazole, or placebo at baseline and again at 6 months were followed and examined fully at 0, 3, 6, and 12 months for helminth infections and anthropometry. Results of treatments indicated that all groups reduced their prevalence and intensity toward the period of the study. Reductions in intensity of both infections in the treatment groups were observed large in 3 and 12 months, whereas at 6 months reached mostly the initial level of infection. There was no significant difference in growth changes between the dewormed (once and twice) and the placebo groups. However, after controlling for some potential confounding factors, there was a significant relationship between reduction of A. lumbricoides infection and height gain at 3 and 12 months (both P < 0.05). In addition, there was a significant association between reduction in T. trichiura infection and increased midarm circumference at 3 and 12 months (P < 0.002 and P < 0.08, respectively). We conclude that treatment of helminth infections in school-age children may improve growth in areas where malnutrition and helminth infections are prevalent.

Animals↗

PubMed1996

Cytoplasmic mRNA for human triosephosphate isomerase is immune to nonsense-mediated decay despite forming polysomes.

Nonsense codons between position 14 within the first exon and position 193 within the penultimate exon of the human gene for triosephosphate isomerase reduce mRNA abundance to 25% of normal. The reduction in abundance is due to the decay of newly synthesized mRNA that copurifies with nuclei. TPI mRNA that copurifies with cytoplasm is immune to decay. We show here that immunity is not due to the failure of nonsense-containing mRNA to form polysomes. This finding indicates that cytoplasmic mRNA, in contrast to nucleus-associated mRNA, may have lost one or more factors that are required for nonsense-mediated decay or gained one or more factors that confer immunity to nonsense-mediated decay.

Animals↗

PubMed1996

Improvements in appetite and growth in helminth-infected schoolboys three and seven weeks after a single dose of pyrantel pamoate.

Appetite and growth were studied in primary schoolboys (6-10 years) infected with Ascaris lumbricoides (86%) and Trichuris trichiura (100%) who received a single dose of pyrantel pamoate (which has little or no effect on Trichuris trichiura) or a placebo. Boys were examined, allocated at random by descending Ascaris egg count to pyrantel (PR, n = 36) or placebo (PL, n = 36) groups, treated, and re-examined 3 and 7 weeks later. The 2 groups did not differ significantly before treatment in helminth infections, appetite, or growth. Three and 7 weeks after treatment, the PR group exhibited significantly greater increases than did the PL group in weight (0.2 kg and 0.4 kg more, respectively) and percentage weight-for-age (0.6% and 1.7% points more, respectively). Appetite increased significantly in the PR group at 3 and 7 weeks (P < 0.0005 and P < 0.01, respectively) but not in the PL group. The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks (both P < 0.0001) but not in the PL group. We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent.

Animals↗

PubMed1995

Not by drugs alone: the fight against parasitic helminths.

With particular reference to parts of eastern and southern Africa the authors outline the dire effects of parasitic worms on people in the tropics and subtropics. Helminth infections can be controlled with drugs but in the long term a more comprehensive approach is required, dealing with poverty, health care and education, living conditions, sanitation and water supplies.

Adolescent↗

PubMed1995

Intestinal helminthiasis, nutritional status, and their relationship; a cross-sectional study in urban slum school children in Indonesia.

In a study of urban slum school children (276 boys and 231 girls), in Ujung Pandang, Indonesia, parasitological and anthropometric exams were cross-sectionally performed to assess prevalence and intensity of helminth infections and nutritional status. Prevalence of Ascaris, Trichuris and hookworm was 92%, 98%, and 1.4%, respectively. 91% children had both Ascaris and Trichuris infections. About half of the Ascaris- and Trichuris-infected children (46% and 58%, respectively) had moderate infections. Stunting was seen in 55% of the children, while wasting was observed in 10%. Boys had lower nutritional status than girls (p < 0.001), based on weight-for-age (WA) and height-for-age (HA) Z-scores. Age had an inverse relationship with WA and HA Z-scores (p < 0.0004). A relationship between helminth infections and nutritional status was observed between log Trichuris egg count and WA and HA Z-scores after controlling for age, sex, and log Ascaris egg count (p = 0.048 for HA Z-score, and p = 0.058 for WA Z-score). The relationship was also found when Trichuris infection was categorized into mild, moderate, and severe infections (p = 0.017 and p = 0.001 for HA and WA Z-scores, respectively). Scheffe's test for multiple mean comparisons showed that Trichuris-infected children with above 1,000 eggs per gram feces had significantly lower nutritional status than lower epg or non-infected children (p < 0.001 and p < 0.05 for HA and WA Z-scores respectively).

Child↗

PubMed1994

Iron supplementation improves appetite and growth in anemic Kenyan primary school children.

A randomized, double-blind, placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children. Sustained-release ferrous sulfate (150 mg) or placebo tablets were provided daily at school for 14 wk. Prior to tablet administration, baseline anthropometry, iron nutritional status (hemoglobin and serum ferritin), parasitic infections and clinical indicators of morbidity were measured. A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack. In addition, each child was asked for a subjective assessment of his or her appetite. Follow-up exams and appetite tests were identical to those at baseline. Findings indicated that provision of iron supplements resulted in improved growth and improved appetite (in terms of both energy intake of the snack and child report of appetite) as compared with children receiving the placebo. The increased energy intake from the snack was 10% of the daily estimated energy intake for children of this same age group living elsewhere in Kenya. Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite.

Anemia, Hypochromic↗

PubMed1994

Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole.

Growth, activity, appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm (93% prevalence), T. trichiura (84% prevalence) and A. lumbricoides (29% prevalence) before and 9 wk after treatment with three 400-mg doses of albendazole (Zentel) or placebo. Fecal samples were examined for helminth eggs using a modified Kato technique. Activity was measured during free-play with motion recorders on the dominant thigh. Children rated their appetites on a 5-point scale. After baseline measurements, children were randomly allocated to the albendazole-treated (n = 28) and placebo (n = 27) groups, treated, and re-examined 9 wk later. At follow-up, egg counts were significantly lower than at baseline in the albendazole-treated group (P < or = 0.002), and gains in activity, reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group. We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity.

Albendazole↗

PubMed1994

Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life.

Frameshift and nonsense mutations within the gene for human triosephosphate isomerase (TPI) that generate a nonsense codon within the first three-fourths of the protein coding region have been found to reduce the abundance of the product mRNA that copurifies with nuclei. The cellular process and location of the nonsense codon-mediated reduction have proven difficult to elucidate for technical reasons. We show here, using electron microscopy to judge the purity of isolated nuclei, that the previously established reduction to 25% of the normal mRNA level is evident for nuclei that are free of detectable cytoplasmic contamination. Therefore, the reduction is likely to be characteristic of bona fide nuclear RNA. Fully spliced nuclear mRNA is identified by Northern (RNA) blot hybridization and a reverse transcription-PCR assay as the species that undergoes decay in experiments that used the human c-fos promoter to elicit a burst and subsequent shutoff of TPI gene transcription upon the addition of serum to serum-deprived cells. Finally, the finding that deletion of a 5' splice site of the TPI gene results predominantly but not exclusively in the removal by splicing (i.e., skipping) of the upstream exon as a part of the flanking introns has been used to demonstrate that decay is specific to those mRNA products that maintain the nonsense codon. This result, together with our previous results that implicate translation by ribosomes and charged tRNAs in the decay mechanism, indicate that nonsense codon recognition takes place after splicing and triggers decay solely in cis. The possibility that decay takes place during the process of mRNA export from the nucleus to the cytoplasm is discussed.

Animals↗

PubMed1994

Helminth parasites, a major factor in malnutrition.

The author discusses the significance of helminth and schistosome infections in exacerbating nutritional problems in many countries, and advocates population-wide treatment where there is clear evidence that this would yield substantial gains in the quality of life.

Ascariasis↗

PubMed1993

Weight gain of Kenyan school children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole.

We studied growth in infected children given one dose (600 mg) or two doses of albendazole per school year. Children were examined and allocated at random within sex by descending hookworm egg count to one of three groups: placebo (n = 93), one dose (1x, n = 96) or two doses (2x, n = 95). Each child was treated and then re-examined and treated 3.6 and 8.2 mo later (Exams 2 and 3). The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight (1.1 and 0.9 kg more, respectively), percent weight-for-age (3.3 and 2.7 percentage points more), percent weight-for-height (3.1 and 2.9 percentage points more), percent arm circumference-for-age (2.3 and 2.0 percentage points more) and triceps and subscapular skinfolds but did not differ significantly from each other. The placebo group showed significant decreases between exams (P < 0.0002) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height, whereas the 1x and 2x groups exhibited significant increases (P < 0.005). At Exam 3, arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95% for hookworm, 42 and 32% for Trichuris and 55 and 87% for Ascaris, respectively. We conclude that one or two doses of albendazole per year resulted in similar growth improvements, despite reinfection, in school-age children in an area where these helminths and poor growth are prevalent.

Albendazole↗