Effects of potassium + magnesium aspartate on muscle metabolism and force development during short intensive static exercise. The effect of feeding different protein-free diets on the recovery and amino acid composition of endogenous protein collected from the distal ileum and feces in pigs. Protein-bound D-amino acids, and to a lesser extent lysinoalanine, decrease true ileal protein digestibility in minipigs as determined with 15N-labeling. Milk and nutrient intake of breast-fed infants from 1 to 6 months: Relation to growth and fatness. Total sulfur amino acid requirement in young men determined by indicator amino acid oxidation with L-[1-13C] phenylalanine. Twin pregnancy: the impact of the Higgins Nutrition Intervention Program on maternal and neonatal outcomes. Ability of the Higgins Nutrition Intervention Program to improve adolescent pregnancy outcome. The effect of varying protein quality and energy intake on the nitrogen metabolism of parenterally fed very low birthweight (<1600 g) infants. The dietary administration of monosodium glutamate or glutamic acid to C-57 black mice for 2 years. Amino acid excesses for young pigs: Effects of excess methionine, tryptophan, threonine or leucine. Effect of excess levels of methionine, tryptophan, arginine, lysine or threonine on growth and dietary choice in the pig. Protein needs of Chilean pre-school children fed milk and soy protein isolate diets. Protein-Energy Requirement Studies in Developing Countries: Results of International Research. The amino acid methionine reduces the valproic acid-induced spina bifida rate in the mouse. Effects of ingested steak and infused leucine on forelimb metabolism in man and the fate of the carbon skeletons and amino groups of branched-chain amino acids. The 24-h pattern and rate of leucine oxidation, with particular reference to tracer estimates of leucine requirements in healthy adults. Validation of the tracer-balance concept with reference to leucine: 24-h intravenous tracer studies with L-[1-13C]leucine and [15N-15N]urea. Moderate exercise at energy balance does not affect 24-h leucine oxidation or nitrogen retention in healthy men. Changes in total body composition during normal and diabetic pregnancy: Relation to oxygen consumption. Leucine uptake by splanchnic and leg tissues in man: Relative independence of insulin levels. Effects of supplemental methionine on antiserum-induced dysmorphology in rat embryos cultured in vitro. Correlations between brain tryptophan and plasma neutral amino acid levels following food consumption in rats. Short-term neuroendocrine effects of a large oral dose of monosodium glutamate in fasting male subjects. Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors. Correlation of aspartate dose, plasma dicarboxylic amino acid concentration, and neuronal necrosis in infant mice. Aspartate-induced neuronal necrosis in infant mice: Protective effect of carbohydrate and insulin. The 24-h whole body leucine and urea kinetics at normal and high protein intakes with exercise in healthy adults. Effect of chronic dietary treatment with L-tryptophan on spontaneous salt appetite of rats. Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting.
Waner, Natural killer cell activity in infants and children excreting cytomegalovirus, J. Kohl, Natural killer cytotoxicity and antibodydependent cellular cytotoxicity of human immunodeficiency virus-infected cells by leukocytes from human neonates and adults, Pediatr. Broxmeyer, Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12, J. Nagler, Effect of interleukin-12 on antitumor activity of human umbilical cord blood and bone marrow cytotoxic cells, Exp. Hahn, Stimulated cord blood lymphocytes have a low percentage of Th1 and Th2 cytokine secreting T cells although their activation is similar to adult controls, Immunol. Buckley, Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution, Annu. Pabst, Distribution of lymphocyte subsets and natural killer cells in the human body, Clin. Kearney, Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants, J. Cheynier, Estimating thymic function through quantification of T-cell receptor excision circles, Methods Mol. Tanaka, Thymoproteasome: probable role in generating positively selecting peptides, Curr. MacDonald, Phenotypic and functional properties of murine thymocytes, I: precursors of cytolytic T lymphocytes and interleukin 2-producing cells are all contained within a subpopulation of "mature" thymocytes as analyzed by monoclonal antibodies and flow microfluorometry, J. Roederer, 11-color, 13-parameter flow cytometry: identification of human naive T cells by phenotype, function, and T-cell receptor diversity, Nat. Vossen, Use of monoclonal antibodies in a study of the development of T lymphocytes in the human fetus, Clin. Broxmeyer, Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated with defective activation of Ras, Proc. Artis, Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites, Immunol. Bryson, Ontogeny of phytohemagglutinin-induced gamma interferon by leukocytes of healthy infants and children: evidence for decreased production in infants younger than 2 months of age, J. Reen, Human recent thymic emigrants-identification, expansion, and survival characteristics, J. Dustin, Visualization of cell-cell interaction contacts-synapses and kinapses, Adv. Sallusto, Understanding the generation and function of memory T cell subsets, Curr. Rowland-Jones, Lessons from the study of T-cell differentiation in persistent human virus infection, Semin. Sallusto, Progressive differentiation and selection of the fittest in the immune response, Nat. Wilson, Regulation of interferon-gamma during innate and adaptive immune responses, Adv. Reen, Interleukin 10, produced in abundance by human newborn T cells, may be the regulator of increased tolerance associated with cord blood stem cell transplantation, Br. Gupta, Disorders of apoptosis: mechanisms for autoimmunity in primary immunodeficiency diseases, J. Wilson, Methylation and demethylation in the regulation of genes, cells, and responses in the immune system, Clin.
Diseases
Although absorbed, these forms do not contribute to meeting the vitamin E requirement because they are not converted to a-tocopherol. Only the 2R-stereoisomeric forms of a-tocopherol are preferentially secreted by the liver into the plasma for transport to tissues. Since the 2S-stereoisomeric forms of a-tocopherol are not maintained in human plasma or tissues, vitamin E is defined in this publication as limited to the 2R-stereoisomeric forms of a-tocopherol to establish recommended intakes. Thus, this person would have an effective total intake of 32 mg/day of a-tocopherol (12 + 20). Group foods into (a) fortified cereal grain foods and specially fortified foods and (b) all others. Moderately fortified ready-to-eat cereals provide approximately 25 percent of the daily value per serving according to the product label, which is currently equivalent to 100 mg of added folate (25 percent of 400 mg). Highly fortified ready-to-eat cereals provide 100 percent of the daily value per serving, or 400 mg of added folate. Combine the folate contributed by all the fortified cereal grains and multiply the result by 1. The other foods in the diet- fruits, vegetables, meats, legumes, and milk products-provide 250 mg of food folate as determined by food composition data. The iron content of each food was determined from appropriate references (expressed as iron content per 100 kcal), thus the iron content of each food was calculated. According to the Third National Health and Nutrition Examination Survey, the median intake of iron by infants is 15. It is estimated that the absorption of iron from fortified cereals is in the range of 6 percent, from breast milk 50 percent, and from meat 20 percent. Mixed population assumes 17 percent oral contraceptive users, 83 percent nonusers, all menstruating. This enables the assessment of population risk where precise estimates are impractical and effectively without impact. May be used in simple computer programs to evaluate adjusted distributions of usual intakes. From this and because the skewness is not extreme, an approximate standard deviation can be calculated. See Acceptable Macronutrient Distribution Ranges Amenorrhea, 291 American Academy of Pediatrics, 179, 314 American Dental Association, 314 Amino acids. See Vitamin C Asparagine, 147 Aspartate, 147 Aspartic acid, 147 Aspirin, 136, 205, 251 Assessment. See also Body fat content; Obesity fat-free mass, 86, 89 undernutrition and, 91 Body fat content. See also Recommended Nutrient Intakes Food Guide, 33 fortification of foods, 247, 249, 324, 333 physical activity recommendations, 95 vitamin B12, 192 Canadian Council on Nutrition, 5 Canadian Paediatric Society, 314 Cancer. See also individual histological sites arsenic and, 421 carbohydrate intake and, 77, 108 carotenoids and, 212 cholesterol and, 142 energy intake and, 76, 84, 92 fat intake and, 76, 136 fiber and, 77, 118, 119, 120 folate and, 245, 246 hormone-related, 77 iron intake and, 337 physical activity and, 77, 95, 98 polyunsaturated fatty acids and, 74, 76 protective effect of nutrients, 76, 77, 111, 118, 245, 246, 382 protein intake and, 76 and riboflavin deficiency, 277 selenium and, 382 sugars and, 77 vitamin D and, 229 Carbohydrate, dietary. See also Energy; individual life stage groups criteria for, 88 defined, 32, 36, 83, 88 derivation of, 36, 82, 83, 84, 88 group applications, 54 indicator of adequacy or inadequacy, 83 individual applications and, 36 by life stage and gender group, 82, 88 physical activity coefficients, 83, 84 uses, 10, 32 Estrogen, 140, 416 Ethanolamine, 125 F Fat, dietary.
An extreme example is the Fiji Islands epidemic of 1875, in which 20,000 people, or about one fourth of the population, are said to have died [403]. The use of live-attenuated measles vaccine in the United States since 1963 has decreased the incidence of measles to less than 1% of its former incidence. Before 1963, there were about 400,000 reported cases of measles annually; a record low of 1497 cases was reported in 1983, but in the late 1980s and early 1990s, there was an increase in the incidence of measles that eventually came under control [371]. Measles occurring despite vaccination may be the result of primary vaccine failure, a "no take" for the vaccine, or secondary vaccine failure because of loss of immunity to measles after vaccination [405,406]. Since the requirement for two doses of measles vaccine in childhood was instituted in 1993, the number of annual cases of measles has declined to an all-time low. The current vaccine coverage in the United States is greater than 90%, which is sufficient to prevent sustained transmission, although it does not prevent imported cases. Incidence of Measles in Pregnant Women Because measles is well controlled in the United States by immunization, it occurs less frequently during pregnancy than chickenpox. A second viremia, more severe and more sustained, disseminates virus to the skin, gut, respiratory tract, and other affected organs. In monkeys, this viremia may occur over 1 week before the appearance of the prodrome or exanthem. Measles virus replicates in and probably destroys lymphocytes in the peripheral blood [412], giving rise to a circulating lymphopenia. The symptoms of measles are probably attributable to inflammation accompanying necrosis of cells in which the virus is replicating. By the time the exanthem appears, 13 to 14 days after infection, measles virus is actively replicating in the skin, gut, and respiratory mucosa. Electron microscopy of biopsy specimens of Koplik spots and cutaneous lesions reveals syncytial giant cells whose nuclear and cytoplasmic inclusions contain aggregates of microtubules that are 15 to 20 nm in diameter and characteristic of paramyxovirus infection [413]. This finding and the observation that convalescent measles serum injected into the skin can prevent the local development of the exanthem [414] suggest that replication of virus per se is directly responsible for the lesions. Nevertheless, it is possible that an interaction between viral antigen and antibody is required. The latter hypothesis is supported by the observation that immunosuppressed children who develop giant cell pneumonia caused by measles virus do not develop a rash and do not elaborate antibodies [396,415]. Virus titers in the viscera have already diminished considerably by the time the exanthem appears, and serum antibodies are readily detectable within 24 hours. There is also experimental evidence that T lymphocytes are important in the development of some symptoms of measles such as the rash and in recovery from the disease [416]. Period of Communicability Measles is more communicable during the prodrome and catarrhal stage of infection than during the period of the exanthem. Dramatic corroboration of this observation was provided during an epidemic in Greenland in 1962 [419]. Deliberate exposure of 400 susceptible persons to disease was achieved by having a patient on the first day of appearance of the exanthem cough twice in the face of each. When the experiment was repeated with a patient during the preexanthematous period, measles was readily transmitted. Patients with measles should be considered infectious from the onset of the prodrome (about 4 days before the appearance of the exanthem) until 3 days after the onset of the exanthem, although the risk of contagion abruptly diminishes 48 hours after the rash appears, concomitant with the appearance of circulating neutralizing antibodies. Measles virus is most readily recovered from respiratory secretions from 2 days before until 1 or 2 days after the onset of the rash. Focal hyaline necrosis of epithelial cells is accompanied by a subepithelial exudate containing predominantly mononuclear leukocytes. It is likely that virus replicates simultaneously in the skin and mucous membranes, but Koplik spots are detected earlier than the exanthem, probably because the epithelium that forms the roof of the lesions is thinner and more translucent in the mucous membranes. Similar lesions containing the characteristic multinucleated giant cells may be widespread throughout the respiratory and gastrointestinal tracts. The pharynx, tonsils, bronchial epithelium, appendix, colon, and lymph nodes have been involved. Necrotic columnar epithelial cells and giant cells are sloughed into the lumen of the bronchi and bronchioles. When this damage is extensive, the regenerating epithelium frequently undergoes squamous metaplasia and is accompanied by bronchial and peribronchial inflammation. Extension of the process into the alveolar septa results in interstitial pneumonitis.
The highest contributors of manganese to the diet are grain products, beverages (tea), and vegetables. Neurotoxicity of orally ingested manganese at relatively low doses is more controversial, but evidence suggests that elevated blood manganese levels and neurotoxicity are possible. Plasma manganese concentrations can become elevated in infants with choleostatic liver disease who are given supplemental manganese in total parenteral nutrition. The requirements for molybdenum are based on controlled balance studies with specific amounts of molybdenum consumed. These enzymes are involved in catabolism of sulfur amino acids and heterocylic compounds such as purines and pyrimidines. A clear molybdenum deficiency syndrome that produces physiological signs of molybdenum restriction has not been achieved in animals, despite major reduction in the activity of these molybdoenzymes. Rather, the essential nature of molybdenum is based on a genetic defect that prevents sulfite oxidase synthesis. Because sulfite is not oxidized to sulfate, severe neurological damage leading to early death occurs with this inborn error of metabolism. Absorption, Metabolism, Storage, and Excretion the absorption of molybdenum is highly efficient over a wide range of intakes, which suggests that the mechanism of action is a passive (nonmediated) diffusion process. However, the exact mechanism and location within the gastrointestinal tract of molybdenum absorption have not been studied. Excretion is primarily through the urine and is directly related to dietary intake. When molybdenum intake is low, about 60 percent of ingested molybdenum is excreted in the urine, but when molybdenum intake is high, more than 90 percent is excreted in the urine. Information on dietary intake of molybdenum is limited because of lack of a simple and reliable analytical method for determining molybdenum in foods. In addition, studies have identified levels of dietary molybdenum intake that appear to be associated with no harm. More soluble forms of molybdenum have greater toxicity than insoluble or less soluble forms. National surveys do not provide percentile data on the dietary intake of molybdenum. Because there was no information from national surveys on percentile distribution of molybdenum intakes, the risk of adverse effects could not be characterized. Legumes, grain products, and nuts are the major contributors of dietary molybdenum. Bioavailability Little is known about the bioavailability of molybdenum, except that it has been demonstrated to be less efficiently absorbed from soy than from other food sources (as is the case with other minerals). It is unlikely that molybdenum in other commonly consumed foods would be less available than the molybdenum in soy. The utilization of absorbed molybdenum appears to be similar regardless of food source. A rare metabolic defect called molybdenum cofactor deficiency results from the deficiency of molybdoenzymes. Few infants with this defect survive the first days of life, and those who do have severe neurological and other abnormalities. There are limited toxicity data for molybdenum in humans; most of the data apply to animals. In the absence of adequate human studies, it is impossible to determine which adverse effects might be considered most relevant to humans. Special Considerations Individuals susceptible to adverse effects: People who are deficient in dietary copper or who have some dysfunction in copper metabolism that makes them copper-deficient could be at increased risk of molybdenum toxicity. However, the effect of molybdenum intake on copper status in humans remains to be clearly established. Information on dietary intake of molybdenum is limited because of lack of a simple and reliable analytical method for determining molybdenum in food.
Syndromes
Influence of breastfeeding and other reproductive factors on bone mass later in life. Vitamin D status, parathyroid hormone and sunlight in Turkish, Moroccan and Caucasian children in the Netherlands. Effects of aging, chronic disease, and multiple supplements on magnesium requirements. Report on the Age Limit to be Adopted in Connection with "Guidelines for a Healthy Diet. Risk of enamel fluorosis associated with fluoride supplementation, infant formula, and fluoride dentifrice use. Rickets in children of rural origin in South Africa: Is low dietary calcium a factor Cellular ions in hypertension, diabetes and obesity: A nuclear magnetic resonance spectroscopic study. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Metabolic responses of adolescent boys to two levels of dietary magnesium and protein. Calcium-regulating hormones and osteocalcin levels during pregnancy: A longtitudinal study. Influence of calcium intake and growth indexes on vertebral bone mineral density in young females. Short-term changes in calcium but not protein intake alter the rate of bone resorption in healthy subjects as assessed by urinary pyridinium cross-link excretion. Magnesium supplementation during pregnancy: A double-blind randomized controlled clinical trial. Influences on skeletal mineralization in children and adolescents: Evidence for varying effects of sexual maturation and physical activity. Reduced rates of skeletal remodeling are associated with increased bone mineral density during the development of peak skeletal mass. Sunshine exposure and serum 25-hydroxyvitamin D concentrations in exclusively breast-fed infants. Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life. Bone mineralization and growth in term infants fed soy-based or cow milk-based formula. Target cells for 1,25dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. The use of epidemiological approaches and meta-analysis to determine mineral element requirements. Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. Metabolic and hemodynamic effects of magnesium supplementation in patients with essential hypertension. Oral iodized oil for correcting iodine deficiency: Optimal dosing and outcome indicator selection. The exchangeable organic iodine pool, and the rates of thyroidal secretion, peripheral degradation and fecal excretion of endogenously synthesized organically bound iodine. A meta-analysis of research on iodine and its relationship to cognitive development. The Damaged Brain of Iodine Deficiency: Cogitive, Behavioral, Neuromotor, Educative Aspects. Evaluation of the iodine intake: Problems of the iodine/creatinine ratio-Comparison with iodine excretion and daily fluctuations of iodine concentration. Thyrotropin and thyroglobulin as an index of optimal iodine intake: Correlation with iodine excretion of 39,913 euthyroid patients. Effect of low dose iodide supplementation on thyroid function in potentially susceptible subjects: Are dietary iodide levels in Britain acceptable Delange F, Benker G, Caron P, Eber O, Ott W, Peter F, Podoba J, Simescu M, Szybinsky Z, Vertongen F, Vitti P, Wiersinga W, Zamrazil V. Thyroid volume and urinary iodine in European schoolchildren: Standardization of values for assessment of iodine deficiency.
Thus, an adequate supply of dietary protein is essential to maintain cellular integrity and function, and for health and reproduction. The requirements for protein are based on careful analyses of available nitrogen balance studies. For amino acids, isotopic tracer methods and linear regression analysis were used whenever possible to determine requirements. Proteins found in animal sources such as meat, poultry, fish, eggs, milk, cheese, and yogurt provide all nine indispensable amino acids and are referred to as "complete proteins. The risk of adverse effects from excess protein intake from food appears to be very low. The data are conflicting on the potential for high-protein diets to produce gastrointestinal effects, changes in nitrogen balance, or chronic disease, such as osteoporosis or renal stones. Amino acids are constituents of protein and act as precursors for many coenzymes, hormones, nucleic acids, and other important molecules. Amino nitrogen accounts for approximately 16 percent of protein weight, and so nitrogen metabolism is often considered to be synonymous with protein metabolism. Amino acids are required for the synthesis of body protein and other important nitrogen-containing compounds as mentioned above. The amino acids that are incorporated into protein are a-amino acids, with the exception of proline, which is an a-imino acid. Although amino acids have been traditionally classified as indispensable (essential) and dispensable (nonessential), accumulating evidence on the metabolic and nutritional characteristics of dispensable amino acids has blurred their definition, forming a third classification called conditionally indispensable. The term conditionally indispensable recognizes that under most normal conditions, the body can synthesize these amino acids. Six other amino acids are conditionally indispensable because their synthesis can be limited under special pathophysiological conditions, such as prematurity in the young infant or individuals in severe catabolic stress. This ability is determined by two factors: digestibility and amino acid composition. Digestibility affects the number and type of amino acids made available to the body. The concept of the "limiting amino acid" has led to the practice of amino acid (or chemical) scoring, whereby the indispensable amino acid composition of a given protein source is compared with that of a reference amino acid composition profile to evaluate the quality of food proteins or their capacity to efficiently meet both nitrogen and indispensable amino acid requirements. Absorption, Metabolism, Storage, and Excretion Amino acids are present in the body as free amino acids or as part of protein. They are available through two major pathways: dietary intake in the form of proteins or de novo synthesis by the body. In the stomach, they are also cleaved into smaller peptides by the enzyme pepsin, which is activated in response to a meal. The proteins and peptides then enter the small intestine, where a variety of enzymes hydrolyze the peptide bonds. The resulting mix of free amino acids and peptides is transported into the mucosal cells. The amino acids are then either secreted into the blood or further metabolized within the cells. Absorbed amino acids pass into the liver, where some are taken up and used and others are circulated to and used by the peripheral tissues. Almost half of the total protein content of the body is represented by only four proteins (myosin, actin, collagen, and hemoglobin). Amino acids are lost in the body by oxidation, excretion, or conversion to other metabolites. Metabolic products of amino acids, such as urea, creatinine, and uric acid, are excreted in the urine; fecal nitrogen losses may account for 25 percent of the obligatory loss of nitrogen. Other routes of loss of intact amino acids are through the sweat and other body secretions and through the skin, nails, and loss of hair. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation.
In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving combination therapy with or without protease inhibitors compared with women receiving zidovudine monotherapy was 0. Levels of maternal viral load at delivery and antenatal antiretroviral therapy were independently associated with transmission. In addition, elective cesarean delivery is recommended if maternal viral load is 1000 copies/mL or greater near delivery. To reduce the development of nevirapine resistance, add lamivudine during labor and maternal zidovudine/lamivudine for 7 days postpartum. In such instances, other antiretroviral agents could be added to the postnatal zidovudine regimen [220]. In addition, most transmission occurs late in pregnancy or at the time of delivery [6,47]. Shorter, less expensive regimens that are more applicable to resource-limited countries were studied in trials. Initial studies focused on regimens that were modifications of zidovudine monotherapy. During labor and delivery, the oral dose of maternal zidovudine was increased to 300 mg every 3 hours. Another placebo-controlled trial in West Africa studied a similar antepartum and intrapartum short-course zidovudine prophylaxis regimen with the addition of a 1-week course of zidovudine to mothers during the postpartum period and reported an efficacy of 38% at 6 months of age in predominantly breast-fed infants [461]. An additional week of postpartum maternal zidovudine therapy did not confer any additional benefit over the antepartum and intrapartum zidovudine-alone prophylaxis regimen. A study in Thailand showed that longer duration of zidovudine prophylaxis (starting at 28 weeks of gestation) is more effective than shorter duration regimens (starting at 36 weeks) [462]. In addition, if the duration of the maternal antepartum regimen is short (<4 weeks), longer infant prophylaxis (4 to 6 weeks) is more effective than shorter infant prophylaxis (3 days to 1 week) [460]. The efficacy of antiretroviral regimens in reducing antepartum and intrapartum transmission is diminished over time in breast-feeding populations. Long-term pooled analysis showed an efficacy of 26% by 24 months of age compared with 37% to 38% efficacy noted in infants at 3 months and 6 months of age in this population with long-term breast-feeding [463]. The overall efficacy of short-course zidovudine is less in breast-feeding populations in sub-Saharan Africa than in formula-fed populations [460,461], and the early efficacy seems to diminish with prolonged breast-feeding [463]. When the efficacy of short-course zidovudine was established, studies explored whether combination antiretroviral regimens are more effective than single-drug prophylaxis. Infants received lamivudine for 6 weeks in addition to the standard 6-week course of zidovudine. The Thailand open-label, nonrandomized trial studied the efficacy of lamivudine added to short-course zidovudine prophylaxis. When the woman has not received any therapy during pregnancy, several efficacious intrapartum and postpartum regimens are available based on data from several international clinical trials. Nevirapine is a very potent non-nucleoside analogue with a long half-life and excellent penetration across the placenta [469]. The single-dose nevirapine regimen is simple, inexpensive, and feasible to implement in resource-limited settings. Addition of single-dose nevirapine can significantly improve the efficacy of other short-course antiretroviral regimens [471,472]. In resource-limited settings, women often present in late labor and do not receive intrapartum antiretroviral prophylaxis in a timely fashion. A study conducted in a breastfeeding population in Malawi evaluated the efficacy of infant antiretroviral prophylaxis when no antepartum or intrapartum maternal antiretroviral therapy was received. This trial compared the efficacy of single-dose infant nevirapine versus single-dose infant nevirapine plus 1-week infant zidovudine; results showed that the combined regimen had a superior efficacy (7. When mothers received intrapartum nevirapine as preexposure prophylaxis, transmission rates were similar, however, for infants who received combined single-dose nevirapine plus zidovudine (6.
Sepsis caused by gram-negative enteric bacilli occurs frequently in infants with galactosemia (see "Pathogenesis"). The incidence of suppurative infections in household contacts of infants without lesions was less than 2%. During the period of observation, one third of the household contacts of the infants became colonized with the same strain. Infections in infants have been associated with bites or licks from household pets. A neonatal case of Campylobacter jejuni sepsis was proven genetically to result from transmission from the family dog [718]. The epidemiologic link between cats and dogs and infection in young infants suggests that parents should limit contact between pets and infants. When fever occurs in the young infant, the incidence of severe disease, including bacterial sepsis, meningitis, and pneumonia, is sufficiently high to warrant careful evaluation and conservative management [719,725]. A careful history of the pregnancy, delivery, nursery experience, interval since discharge from the nursery, and infections in the household should be obtained. Physical examination should establish the presence or absence of signs associated with congenital infection and lateonset diseases. Risk stratification algorithms have been evaluated to incorporate ancillary clinical testing in hopes of supplementing the often incomplete picture that emerges from history and physical examination [725]. The "Rochester criteria" for analysis of febrile infants, originally proposed by Dagan and colleagues [722], used criteria such as normal peripheral leukocyte count (5000 to 15,000/mm3), normal absolute band neutrophil count (<1500/mm3) and absence of pyuria to identify low-risk patients. When Ferrera and coworkers [721] retrospectively applied these criteria to the subset of patients in their first 4 weeks of life, 6% of the neonates fulfilling low-risk criteria had serious bacterial infections. Similarly, when groups of febrile newborns were retrospectively stratified as low risk by the "Philadelphia criteria" [728] or "Boston criteria" [729] developed for older infants, it became apparent that 3. Although a peripheral blood cell count is routinely ordered, it is not sufficiently discriminatory to preclude the mandatory collection of blood for culture [730,731]. In contrast to older infants [732], the presence of signs consistent with a viral upper respiratory tract infection in the neonate does not obviate the need for a full diagnostic evaluation. Neonates infected with respiratory syncytial virus had equivalent rates of serious bacterial infection as neonates testing negative for the virus [733]. More recent data suggest, however, that febrile infants less than 60 days of age positive for influenza virus infection may have lower rates of bacteremia and urinary tract infection than similar infants without influenza infection [734]. Because of the high rates of serious bacterial infections, guidelines prepared by Baraff and colleagues [719] for the management of infants and children with fever without source state that all febrile infants younger than 28 days should be hospitalized for parenteral antibiotic therapy, regardless of the results of laboratory studies. Michael Marcy, Carol Baker, and Debra L Palazzi contributed to this chapter in earlier editions. The authors are indebted to these scholars for their roles in the preparation of this chapter. Winfred, the incidence of neonatal infections in the nursery unit at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, East Afr. Bekassy, Changing pattern of neonatal meningitis in Sweden: a comparative study 1976 vs. Lancefield, Serologic differentiation of human and other groups of hemolytic streptococci, J. Deringer, Group B streptococcal toxic shock-like syndrome: report of a case and purification of an associated pyrogenic toxin, Clin. Larsen, Streptococcal puerperal sepsis and obstetric infections: a historical perspective, Rev. Kaplan, Suppurative group A b-hemolytic streptococcal infections in children, Pediatrics 89 (1992) 743. Mortimer, Group A streptococcal infections in newborn nurseries, Pediatrics 46 (1970) 849. Klein, Concurrent epidemics of Staphylococcus aureus and group A streptococcus disease in a newborn nursery-control with penicillin G and hexachlorophene bathing, Pediatrics 51 (1973) 383. Howard, A prolonged nursery epidemic associated with a newly recognized type of group A streptococcus, J. Cooper, Group A beta-hemolytic streptococcus causing disseminated intravascular coagulation and maternal death, Lancet 1 (1988) 595.
Nitazoxanide is effective therapy of immunocompetent adults and children with cryptosporidiosis [1122]. Because illness is usually self-limited in the normal host, attention to fluid, electrolyte, and nutritional status is usually sufficient. Enteric isolation of hospitalized infants with this illness is appropriate because of the high infectivity. Several studies suggest that the risk of infection early in life may be decreased by breast-feeding [1116,1123], Using appropriate filtration systems in areas where water treatment is minimal can have a significant impact in decreasing cases of cryptosporidiosis [1124]. Six distinct rotavirus groups (A through F) have been identified serologically based on common group antigens [1130,1131], of which three (A, B, and C) have been identified in humans [1126]. Because group A rotaviruses represent more than 95% of isolated strains in humans worldwide, further discussion focuses on this group. Group A rotaviruses are subclassified into serotypes based on neutralization epitopes located on the outer capsid. Combining G antigenic with P antigenic and genetic typing, a specific rotavirus strain can be identified: P antigenic type (P genetic type), G type. Some of these strains seem to be associated with occurrence of asymptomatic infections, although the existence of naturally acquired asymptomatic strains is controversial. Neonates can also be symptomatically infected with unusual animal-human reassortant strains in areas of poor sanitary conditions [1146]. Pathogenesis Although mechanisms involved in rotavirus pathogenesis have been extensively studied, current understanding of the exact mechanisms involved in human disease is only partial and may be subject to significant conceptual modifications as more knowledge is obtained in the future. Lactase, which is present only on the brush border of the differentiated epithelial cells at these sites, may act as a combined receptor and uncoating enzyme for the virus, permitting transfer of the particles into the cell [1152]. Perhaps for this reason, infection is limited to the mature columnar enterocytes; crypt cells and cryptderived cuboidal cells, which lack a brush border, seem to be resistant to rotaviral infection [1152,1153]. The upper small intestine is most commonly involved in rotavirus enteritis, although lesions may extend to the distal ileum and rarely to the colon [1156,1157], Interaction between intestinal cell and rotavirus structural and nonstructural proteins occurs, resulting in death of infected villous enterocytes [1158]. When infected, the villous enterocyte is sloughed, resulting in an altered mucosal architecture that becomes stunted and flattened. The gross appearance of the bowel is usually normal; however, under the dissecting microscope, scattered focal lesions of the mucosal surface are apparent in most cases. Light microscopy also shows patchy changes in villous morphology, compatible with a process of infection, inflammation, and accelerated mucosal renewal. The villi take on a shortened and blunt appearance as tall columnar cells are shed and replaced by less mature cuboidal enterocytes [1148,1150,1159]. Ischemia may also play a role in the loss and stunting of villi [1160] and activation of the enteric nervous system; active secretion of fluid and electrolytes may be another pathogenic mechanism [1161]. During the recovery phase, the enteroblastic cells mature and reconstruct the villous structure. Because of the loss of mature enterocytes on the tips of the villi, the surface area of the intestine is reduced. More recent studies suggest that destruction of mature enterocytes does not seem to be a critical element in the pathogenesis of rotavirus infection. The exact mechanism of action of this protein at the intestinal level is only partially understood, but known to be different from the action of bacterial enterotoxins. Rotavirus antigenemia and viremia seem to be common events during rotavirus infection, a concept that revolutionized understanding of this infection [1168]. These events could partly explain the sporadic reports of systemic disease associated with rotavirus intestinal infections mentioned further on.
References:
