The Global Burden of Disease caused by the 3 major intestinal nematodes is an estimated 22n1 million disability-adjusted life-years (DALYs) lost for hookworm, 10n5 million for Ascaris lumbricoides, 6n4 million for Trichuris trichiura, and 39n0 million for the three infections combined (as compared with malaria at 35n7 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.

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 insulinlike growth factor-1 (IGF-1), increases in tumor necrosis factor-α (TNF-α) 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.

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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.

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 shutof 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.Triosephosphate isomerase (TPI; EC 5.3.1.1) catalyzes the interconversion of dihydroxyacetone phosphate and glyceraldehyde 3-phosphate and has an important role in glycolysis, gluconeogenesis, fatty acid synthesis, and the pentose shunt (29). Frameshift and nonsense mutations within the human TPI gene that result in a nonsense codon within the first three-fourths of the translated portion of TPI mRNA reduce the abundance of TPI mRNA to 20 to 30% of normal (10,11). Since the reduction is characteristic of both nuclear and cytoplasmic cell fractions and is not attributable to a decrease in the half-life of cytoplasmic TPI mRNA, the degradative process has been rationalized to involve nuclear TPI RNA (10, 11). Such deductive reasoning presents a dilemma when one considers a plausible degradative mechanism because nonsense codons are known to be recognized only in the cytoplasm during the process of mRNA translation-a process that in mammalian cells is generally thought to be spatially and temporally distinct from the processes of nuclear RNA metabolism. Indeed, degradation is likely to be initiated by the premature termination of cytoplasmic mRNA translation, since the reduction in the abundance of a nonsense codoncontaining mRNA is abrogated by a hairpin structure in the 5' untranslated region, which acts in cis to inhibit translation in...