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Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

In 2007, the blood collection rate in Nicaragua was 106.6 units per 10,000 inhabitants. Voluntary donation was 39%. The health authorities decided to pursue self sufficiency of blood by eliminating replacement donation and consolidating blood processing in two centers. Replacement donation was terminated in 2009, voluntary donation reached 100% in 2010, and the blood collection rate increased to 125.9 in 2011. The rate of red blood cell transfusion improved from 96.0 to 119.1 units per 10,000 during the 4-year period. The political will of the government, pertinent technical leadership, and a country-wide approach were essential for attaining those goals.

Background: Blood transfusions carry risks of untoward reactions, including the transmission of infections, such as hepatitis B and C. Proper blood donor recruitment and selection, and adequate laboratory screening for infectious markers diminish the risk of transfusion-transmitted infections. Objectives: To estimate the potential risk of acquiring transfusion-transmitted infections by hepatitis B or hepatitis C in 24 Caribbean countries during the period of 1996 to 2003. Study design: Official national reports for 1996, 2000–2003 of the yearlynumber of blood donors, screening coverage, and prevalence of serological markers for infectious diseases were used to estimate the risk of patients receiving an HBV- or HCV-positive unit of blood, and of developing an infection after receiving a positive unit. Estimates of number of infections transmitted through transfusion and number of infections prevented by screening of blood were also obtained. Results: During the period analyzed, HBV screening coverage among blood donors was 100% in all countries with the exception of Grenada (0% in 1996) and Saint Lucia (99.5% in 2002). For HCV, only 10 countries reported universal screening in 1996, while 15 did in 2003. The number of countries that did not screen any units for HCV decreased from 11 in 1996 to five in 2003. In general, high prevalence rates of HBV (10–75 per 1000 donors) and HCV (7–19.3 per 1000 donors) markers were found in the majority of countries. We estimated that 235 infections by HCV (1:12471 donations) and two infections by HBV (1:1465373) were transmitted through transfusion because of lack of screening. On the other hand, screening of blood for transfusion prevented 21 005 HCV and 22 100 HBV infections. Conclusions: Blood donor recruitment and coverage of screening for transfusion-transmitted infections, especially HCV, mustbe improved in the Caribbean countries.

OBJETIVO: Obtener información de base sobre los conocimientos, actitudes y prácticas relacionados con la donación voluntaria de sangre, así como la capacidad instalada de los bancos de sangre para la atención de donantes. MÉTODOS: El estudio se realizó en 15 países de la Región: Argentina, Bolivia, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Jamaica, Nicaragua, Panamá, Paraguay, Perú, República Dominicana y Venezuela, con la cooperación técnica de la Organización Panamericana de la Salud, oficina regional de la Organización Mundial de la Salud. Se utilizó una metodología formativa cualitativa mediante entrevistas a donantes, público en general y personal de salud, así como observación directa, grupos focales, pruebas de conocimientos y revisión documental. RESULTADOS: Se identificaron el conocimiento de las personas sobre la donación, sus creencias, percepciones y actitudes, sus barreras y motivaciones, al igual que los medios más eficaces para transmitir el mensaje a favor de la donación voluntaria. CONCLUSIONES: Esta información servirá como base para diseñar una estrategia en los países encaminada a promover la captación y lealtad de los donantes voluntarios de sangre. Esta estrategia podrá ser el sustento para llevar a la práctica los cambios necesarios en la atención y motivar a los donantes a regresar con regularidad a donar sangre.

OBJECTIVES: This article has two objectives: (1) to present for countries and territories of the Region of the Americas data on the number of blood donations, proportion of voluntary blood donors versus remunerated blood donors, coverage of screening for infectious agents, and separation of donated blood into its components and (2) to explore the relationships of those characteristics with economic and organizational factors in the countries and territories. METHODS: We carried out comparative analyses using population and health information gathered annually by the Pan American Health Organization (PAHO) from national health officials from the countries in the Americas, as well as economic information (gross national product (GNP) per capita) obtained from publications of the World Bank. RESULTS: There is a direct correlation between the availability of blood for transfusion and GNP per capita. Seven countries with a GNP per capita above US$ 10 000 per year account for 38% of the Regional population but 68% of the Regional blood donations. Voluntary blood donation is more common in the countries with better blood availability. There is no association between GNP per capita and coverage of screening for infectious agents. Nevertheless, of the six countries with a GNP per capita below US$ 1 000, only one of the six screens all units for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg). Countries with a higher proportion of voluntary blood donors tend to have lower prevalence rates of infectious markers. Separation of blood into its components is also more common in countries with higher blood donation rates. CONCLUSIONS: The availability, safety, and quality of blood for transfusion in the Americas needs to be improved. As part of that effort, national policies and strategies must be put into place so that the resources already allocated for blood services are better utilized.OBJETIVOS: Este artículo tiene dos objetivos: 1) presentar para los países y territorios americanos datos acerca del número de donaciones de sangre, la proporción de donantes voluntarios y remunerados, la cobertura con pruebas para el tamizaje de agentes infecciosos y la separación de sangre donada en sus diversos componentes, y 2) explorar las relaciones entre estas características y factores económicos y de organización en los países y territorios. MÉTODOS: Llevamos a cabo análisis comparativos usando información poblacional y sanitaria obtenida anualmente por la Organización Panamericana de la Salud (OPS) de las autoridades de salud de los países de las Américas, así como información económica (producto nacional bruto (PNB) per cápita) sacada de publicaciones del Banco Mundial. RESULTADOS: Hay una correlación directa entre la disponibilidad de sangre para transfundir y el PNB per cápita. Siete países con un PNB per cápita mayor de US$ 10 000 anuales representan 38% de la población de la Región, pero 68% de las donaciones en esta. La donación voluntaria de sangre es más común en países donde hay más disponibilidad de sangre. No hay ninguna asociación entre el PNB per cápita y la cobertura con pruebas para el tamizaje de agentes infecciosos. No obstante, de los seis países con un PNB per cápita menor de US$ 1 000, solamente uno somete a tamizaje todas las unidades de sangre para la detección del virus de la inmunodeficiencia humana (VIH), el virus de la hepatitis C (HCV), y el antígeno superficial del virus de la hepatitis B (HBsAg). Los países con una mayor proporción de donantes voluntarios suelen tener una menor prevalencia de positividad a marcadores de infección. La separación de la sangre en sus diversos componentes es también más frecuente en países con tasas más elevadas de donación de sangre. CONCLUSIONES: La disponibilidad, seguridad y calidad de la sangre para transfusión en países de las Américas deben mejorarse. Como parte de una iniciativa de este tipo, hay que poner en marcha políticas y estrategias nacionales a fin de lograr que los recursos ya adjudicados a los servicios de transfusión de sangre sean mejor aprovechados.

Analysis of IgA, IgM, and IgG antibodies against Escherichia coli O6, its lipopolysaccharide (LPS), and Shigella flexneri were performed in the milk of moderately undernourished Guatemalan women receiving either a low or a high calorie supplement, using SDS-PAGE. As expected, the immunostaining analysis of milk antibodies showed that IgA was the predominant isotype in both groups. Concerning the other Igs, antibodies against O6 LPS were mainly of the IgM isotype, whereas IgG antibodies were more prominent than IgM against the bacterial whole cell preparations. Seven to nine distinct bands, ranging in molecular mass from 13.5 to 109 kD were selected for each antigen to compare the milk antibodies between the two groups of women. After a 20-wk supplementation period, the IgA and IgG antibodies to the E. coli, O6 LPS, and S. flexneri were not found negatively affected by a low calorie intake. A significantly lower immunostaining intensity was, however, obtained for the low calorie intake group regarding the IgM antibody activity against four high molecular mass bands of the E. coli whole cell preparation. A decreased immunostaining intensity was also found in the same group for IgM antibodies against two bands of E. coli O6 LPS when analyzing paired samples collected at d 0 and wk 20. No differences were found for IgM antibodies against any of the S. flexneri antigens. In conclusion, the results suggest that low calorie intake does not significantly affect the production of milk IgA antibodies to E. coli and S. flexneri antigens in these women. Still, IgM antibodies against certain proteins and LPS molecules of E. coli may be decreased. IgG antibodies, although also present in milk, seemed to be directed mainly against bacterial proteins and not to LPS.

Fecal excretion of astroviruses was monitored in 321 children, 0 to 3 years old, living in the rural highlands of Guatemala. During the longitudinal study, from February 1987 to February 1989, we examined 5,000 stool specimens, including 1,805 collected during 1,369 episodes of diarrhea, 830 collected during the convalescent week, and 216 and 244 collected 2 weeks and 1 week, respectively, before the onset of diarrhea. Routine specimens were taken once a month from every child who had been free from diarrhea for at least three consecutive weeks. Of the children, 124 (38.6%) excreted astroviruses during the study. In total, we identified 184 infections by astroviruses. Of the samples collected 2 weeks and 1 week before the initiation of symptoms, 0.9 and 4.9%, respectively, were positive, while 7.3% of the diarrhea episodes were associated with astroviruses. Of the convalescent specimens, 3.4% were shown to be positive; 2.4% of the 1,905 specimens taken in diarrhea-free periods contained astroviruses. Infections by other potential enteropathogens were documented in 54 and 65% of the asymptomatic and symptomatic astrovirus infections, respectively. Diarrhea associated with astroviruses alone had a median duration of 5 days and was associated with vomiting in 8.6%, with fever in 17.1%, with dehydration in 5.7%, and with loss of appetite in 34.3% of the episodes. Diarrhea due to astroviruses was accompanied by negative changes in weight gain. Astrovirus diarrhea contributes to the high morbidity observed in young children living under poor conditions and has a deleterious effect on their nutritional status.

Acute respiratory tract infections (ARI) were studied during a 2-year period in 521 preschool children living in a marginal area of Guatemala City. There were 3,646 episodes of ARI detected during 26,329 child-weeks at risk, for an incidence of 14 per 100 child-weeks or 7.2 episodes per child per year. The median duration of ARI episodes was 11 days. The highest incidence of ARI was observed in children 6-23 months old. Boys had more respiratory tract illnesses than did girls; the presence of a cigarette smoker in the household was associated with higher morbidity. Acute lower respiratory tract illnesses (ALRI) were more common among younger infants 0-5 months old, with nutritional status having no apparent effect. Parental formal education and crowding in households were found to be directly related to the incidence of ALRI. In general, ARI morbidity interfered with appropriate physical growth.

OBJECTIVES: This article has two objectives: (1) to present for countries and territories of the Region of the Americas data on the number of blood donations, proportion of voluntary blood donors versus remunerated blood donors, coverage of screening for infectious agents, and separation of donated blood into its components and (2) to explore the relationships of those characteristics with economic and organizational factors in the countries and territories. METHODS: We carried out comparative analyses using population and health information gathered annually by the Pan American Health Organization (PAHO) from national health officials from the countries in the Americas, as well as economic information (gross national product (GNP) per capita) obtained from publications of the World Bank. RESULTS: There is a direct correlation between the availability of blood for transfusion and GNP per capita. Seven countries with a GNP per capita above US$ 10 000 per year account for 38% of the Regional population but 68% of the Regional blood donations. Voluntary blood donation is more common in the countries with better blood availability. There is no association between GNP per capita and coverage of screening for infectious agents. Nevertheless, of the six countries with a GNP per capita below US$ 1 000, only one of the six screens all units for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg). Countries with a higher proportion of voluntary blood donors tend to have lower prevalence rates of infectious markers. Separation of blood into its components is also more common in countries with higher blood donation rates. CONCLUSIONS: The availability, safety, and quality of blood for transfusion in the Americas needs to be improved. As part of that effort, national policies and strategies must be put into place so that the resources already allocated for blood services are better utilized.

SUMMARY Appropriate selection of donors, use of sensitive screening tests, and the application of a mandatory quality assurance system are essential to maintain the safety of the blood supply. Laws, decrees, norms, and/or regulations covering most of these aspects of blood transfusion exist in 16 of the 17 countries in Latin America that are the subject of this review. In 17 countries, there is an information system that, although still incomplete (there are no official reports on adverse events and incidents), allows us to establish progress made on the status of the blood supply since 1993. Most advances originated in increased screening coverage for infectious diseases and better quality assurance. However, in 2001 to 2002, tainted blood may have caused infections in 12 of the 17 countries; no country reached the number of donors considered adequate, i.e., 5% of the population, to avoid blood shortages, or decreased significantly the number of blood banks, although larger blood banks are more efficient and take advantage of economies of scale. In those years, paid donors still existed in four countries and replacement donors made up >75% of the blood donors in another eight countries. In addition, countries did not report the number of voluntary donors who were repeat donors, i.e., the healthiest category. In spite of progress made, more improvements are needed.

To obtain baseline data for countries of the Americas on knowledge, attitudes, and practices related to voluntary blood donation as well as on the current level and quality of services that blood banks provide to donors.The study was conducted in 15 countries in the Americas: Argentina, Bolivia, Colombia, Costa Rica, Cuba, the Dominican Republic, Ecuador, El Salvador, Guatemala, Jamaica, Nicaragua, Panama, Paraguay, Peru, and Venezuela. Technical cooperation for the study came from the Pan American Health Organization. A qualitative formative methodology was applied, utilizing interviews with donors, health workers, and members of the general public; direct observation; focus groups; knowledge tests; and a review of documents.Information was generated on people's knowledge of donation; their beliefs, perceptions, attitudes, and motivations; and their barriers to donating. Knowledge was also gained as to the best means for disseminating messages supporting voluntary donation.This information will serve as a foundation for designing a strategy in the countries of the Americas that is aimed at establishing and building the loyalty of voluntary blood donors. This strategy can support the implementation of changes needed in the care of donors, and it can also help in motivating donors to regularly return to donate blood.

The potential risk of acquiring a transfusion-transmitted infection by the human immunodeficiency virus (HIV), hepatitis B (HBV) virus, hepatitis C (HCV) virus, or Trypanosoma cruzi was estimated for seven South American and five Central American countries during the period 1994-1997. The estimates were based on official national reports of the number of donors, blood screening coverage, and prevalence of serologic markers for infectious diseases. Coverage of screening in 1997 was 100% in 12 and 11 countries for HIV and HBV respectively. Complete screening for HCV was reported by only one country in 1994 and by six in 1997. For T. cruzi, the number of countries with 100% screening coverage increased from two in 1994 to four in 1997. In 1994, three countries showed risk of transfusion-transmitted infections for HIV, seven for HBV, eight for HCV, and seven for T. cruzi. The risk of receiving an infected blood unit and acquiring a transfusion-transmitted infection has been reduced with time in 10 of the 12 countries due to improvements in screening coverage. In Uruguay, the risk was theoretically nil from 1994-1997 because at the beginning of the study period they already had 100% blood donor screening for all infectious diseases transmitted by blood. In 1994, Colombia and Venezuela had the highest health risk associated with blood transfusion (spreading index of 101 and 62, respectively); during the period 1996-1997, Costa Rica presented the highest figures (spreading index of 53 and 83, respectively). The analysis of the potential risk associated with transfusion of tainted blood highlights the need for continuous monitoring of the safety of blood supply.

Objective: To investigate the expression of αv integrin in developing human embryos. Design: Observational study. Setting: University medical center. Patient(s): Women undergoing IVF cycles. Intervention(s): Immunofluorescent monoclonal antibodies against αv integrin were used to stain human preimplantation embryos. Main Outcome Measure(s): Immunofluorescence microscopy and computerized image analysis were used to evaluate both qualitative and quantitative expression of integrins in human embryos. Result(s): The αv integrin subunit was found to be expressed in human embryos throughout their development (from two-cell stage up to blastocyst). The expression of αv integrin subunit gradually increased throughout embryo development as measured quantitatively by image analysis. Conclusion(s): The expression of αv integrin subunit throughout the development of preimplantation human embryos reinforces the concept of a role for integrins in the process of implantation.

Objective: To determine whether blastocyst transfer is of benefit to patients with multiple IVF failures. Design: Retrospective cohort study. Setting: The George Washington University Medical Center. Patient(s): Patients undergoing IVF between October 1, 1997, and November 30, 1998, who had previously undergone three or more unsuccessful IVF cycles. Patients who had at least three embryos at the 8- to 12-cell stage available on day 3 were eligible for the study. Intervention(s): Patients were given the option of day 3 ET (group A) or blastocyst transfer (group B). Main Outcome Measure(s): Blastocyst-formation rate, clinical pregnancy rate (PR) per transfer, and implantation rate per transfer. Result(s): Groups A and B were similar in terms of age, the number of previous failed IVF cycles, fertilization rate, and the number of fertilized oocytes per cycle. The blastocyst-formation rate was 51.0%. Clinical pregnancy and implantation rates per transfer were statistically significantly higher in the blastocyst-transfer group. There were no multiple pregnancies after blastocyst transfer. Conclusion: Blastocyst transfer increases implantation rates and PRs in patients with multiple failed IVF cycles, without increasing the risk of multiple pregnancy.

Intestinal helminths are among the most common infections in school-age children. Of 246 children, aged 7-12 years, attending school in rural Guatemala, 91% carried Ascaris lumbricoides and 82% carried Trichuris trichiura. These children were randomly assigned to receive either albendazole or placebo at 0 and 12 weeks in a 'double-blind' study of the effects of deworming on indicators of school performance. Albendazole successfully rid the children of Ascaris but it was less effective against Trichuris. The children's performance in tests of reading and vocabulary were measured at 0 and 24 weeks, the Peabody picture vocabulary test was given at 24 weeks, and attendance was measured throughout the school year. Comparison of the treated and placebo groups showed no positive effect of deworming. The treated children were largely free of Ascaris for at least 6 months, but during that period we could not detect any improvement in reading, vocabulary, or attendance. The effects of being Trichuris-free were not examined because of the limited effectiveness of albendazole against this worm at the dosage used.

In Guatemala, as in many other developing countries, diarrhoeal diseases continue to be the most important public health problem, with a high incidence and a heavy toll in childhood mortality. Among the many causes of diarrhoea, C. jejuni 1 is seldom reported in the routine search for pathogens due to the special conditions it requires for isolation and growth. This infection has been associated with mild, acute or persistent diarrhoea1. In Guatemalan children, seven percent of the C. jejuni infections result in acute dysentery2. As C. jejuni is only susceptible to erythromycin, it is crucial to make the differential diagnosis from dysentery caused by Shigellae or by Entamoeba histolytica, in order to prescribe the appropriate treatment3.

Undernutrition affects the immune response and, therefore, might worsen the outcome of infections.1,2 This is especially important in developing countries where the prevalence of infectious diseases is high.

En este artículo se resumen la misión y las funciones de los servicios de sangre de un país y se examinan los componentes necesarios para el funcionamiento adecuado y eficiente de un sistema nacional de servicios de sangre. La sangre para transfusión es un recurso nacional y, por tanto, las autoridades sanitarias deben garantizar su disponibilidad, seguridad, calidad y uso eficiente. Para alcanzar estas metas, cada país debe tener un marco jurídico reglamentario para los centros donde se extrae, procesa y transfunde la sangre. Las leyes y los reglamentos sirven de base para la organización del sistema de servicios nacional, identifican las tareas de los interesados directos y garantizan la disponibilidad de los recursos que necesita el sistema. Esas leyes y reglamentos deben basarse en sólidos criterios médicos y técnicos. Dentro de este marco, es importante tener presentes las diversas funciones de los distintos departamentos del ministerio de salud, así como de otras instituciones, organizaciones no gubernamentales y grupos académicos y de los profesionales vinculados con el sistema nacional de servicios de salud.

En este artículo se resumen la misión y las funciones de los servicios de sangre de un país y se examinan los componentes necesarios para el funcionamiento adecuado y eficiente de un sistema nacional de servicios de sangre. La sangre para transfusión es un recurso nacional y, por tanto, las autoridades sanitarias deben garantizar su disponibilidad, seguridad, calidad y uso eficiente. Para alcanzar estas metas, cada país debe tener un marco jurídico reglamentario para los centros donde se extrae, procesa y transfunde la sangre. Las leyes y los reglamentos sirven de base para la organización del sistema de servicios nacional, identifican las tareas de los interesados directos y garantizan la disponibilidad de los recursos que necesita el sistema. Esas leyes y reglamentos deben basarse en sólidos criterios médicos y técnicos. Dentro de este marco, es importante tener presentes las diversas funciones de los distintos departamentos del ministerio de salud, así como de otras instituciones, organizaciones no gubernamentales y grupos académicos y de los profesionales vinculados con el sistema nacional de servicios de salud.

In developing countries, Campylobacter jejuni causes diarrhea and dysentery, especially in children less than one year of age. Breast feeding protects against infectious diarrhea, with milk IgA antibody playing a determining role. Therefore, it has been proposed to increase the protective effect of human milk by vaccinating women of child-bearing age. To identify antigens which may induce protective breast-milk IgA, we analyzed 60 strains of C. jejuni isolated from asymptomatically- and symptomatically-infected breast-fed children less than 12 months of age. Surface antigens of C. jejuni, separated by polyacrylamide gel electrophoresis, were probed with breast milk collected concurrently with the fecal sample from which C. jejuni was isolated, and specific IgA was developed by immunoblotting. Our results indicate that milk antibodies against three high molecular weight bacterial surface antigens of 95, 110 and 185 kDa are involved in protection of infants infected with C. jejuni (p = 0.00964 for one-tailed Fisher's exact test).

Publisher Summary This chapter discusses the role of breast milk in neonatal host defense. Human milk is rich in host defense factors, although so far only SIgA antibodies have been shown to be protective per se. Defense via human milk may largely be anti-inflammatory. Thus, milk lactoferrin seems to be able to prevent IL-6 release after exposure of human macrophages and gut epithelial cells to lipopolysaccharides (LPS). The start of breast-feeding is traditionally delayed during the first days of life in some, possible many, societies in the developing world, for example, in Pakistan. Thereafter partial breast-feeding is most common with the addition of animal milk and extra water using a bottle, especially during the hot season when there is increased incidence of diarrhea. Such partial breast-feeding protects strongly against neonatal sepsis and early diarrheal diseases. Breast-feeding also protects against necrotizing enterocolitis. Mortality in lower respiratory tract infections is decreased as well by breast-feeding.

We conducted a randomized, double-blind, placebo controlled clinical trial of oral gentamicin (10 milligrams/kilogram body weight/day for five days) in treatment of unselected cases of persistent diarrhea (duration 14-18 days at initiation of treatment) among 3-36-month-old children in a rural Guatemalan community. Following random assignment of each child to a treatment group, the appropriate dose of gentamicin or placebo was administered to the child three times daily by a study nurse; this nurse also identified the presence or absence of diarrhea on each day of treatment and for the next two days. Cure was defined as cessation of diarrhea during the five-day treatment period, sustained through at least the two days after completion of treatment. Among 92 evaluable cases who entered the clinical trial, there was essentially no difference in cure rate between gentamicin and placebo treatment groups (42% versus 43%). Enteroadherent strains of Escherichia coli were identified in 46% of children tested in this trial; no significant difference existed between treatment groups in frequency of isolation of this or any other enteropathogen. Among 40 children having successful duodenal cultures immediately prior to beginning treatment, > or = 10(4) aerobic organisms per milliliter of fluid were identified in 12 (30%); treatment groups did not differ substantially with respect to proportion of children identified with this level of duodenal microbial colonization. Failure of gentamicin treatment did not appear to be explained by emergence of resistance, although a small number of resistant enteropathogens were identified near the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective, longitudinal two-year study to determine the epidemiology of persistent (> or = 14 days' duration) diarrhea in rural children of Guatemala was undertaken. Three-hundred and twenty-one children aged 0-35 months were kept under surveillance by twice-a-week home visits. The overall incidence of diarrhea was 0.147 per child-week; the incidence of persistent diarrhea was 0.014 per child-week. The peak of persistent diarrhea was observed in infants below six months of age, with a continuous decline thereafter. This trend in incidence of persistent diarrhea was associated with a higher proportion (16%) of illnesses persisting for more than 13 days in children younger than six months of age as compared to children 30-35 months old (4%). Males had more diarrhea (0.156 per child-week) than females (0.139 per child week). Among children above 18 months of age, the proportion of episodes that lasted for more than 13 days was lower in females than in males.

Human colostrum S-IgA and mature breast milk contain large quantities of secretory IgA (S-IgA)1–3. In general, the concentration of milk SIgA is higher in the early postpartum period; than in the later stages of lactation3–5. The content of S-IgA is the result of the additive presence of a great variety of specific S-IgA antibodies that are formed locally in the mammary gland by lymphocytes that had been primed at the intestinal level by microbial and food antigens, and that migrated to the mammary gland under the influence of hormones6–8. In such a way, antibodies directed against Shigella,Salmonella and Escherichia coli somatic antigens, Vibrio cholera and E. coli toxins, rota- and polioviruses, and cow milk, black beans and soy beans proteins, have been detected in human colostrum and milk samples obtained in different ecosystems1,9–14. The ingestion of human milk containing high levels of specific antibodies has been shown to be associated with protection against diarrheal illnesses15,16 and food allergies17 in the breast-fed infants. Nevertheless, prospective studies have demonstrated that the presence and levels of specific S-IgA antibodies in milk do not remain constant during lactation18,19, suggesting that its protective capacity also varies over time.

Focal group interviews on indigenous perceptions and reported management of childhood diarrhea were conducted in 1987-88 in Guatemala as a part of a prospective epidemiological field study of chronic diarrhea. Six cognitive schemata were identified, each with specific causes, a linked progression of concepts, symptoms, signs, and diagnostic characteristics. Nearly all were related to the humoral theory of disease, including the concept of evil eye. Diarrheal disease was conceptualized in the village as a set of processes which could be either "hot" or "cold" rather than as an unchanging single-symptom entity occupying only one spot on the humoral continuum. Clarification of the temporal relationship between concepts was found to be essential to the understanding of these indigenously-defined schemata. Stool color reflecting humoral theory was the primary concept used in household-level diagnosis. Reported behavior associated with these cognitive schemata (traditional treatments, pharmaceutical and dietary management) showed remarkable constancy, and adhered for the most part to the humoral concept of equilibrium. These included the use of oral rehydration solutions (ORS) and liquids. The applied importance of humoral theory to home-based use of ORS is discussed briefly as is the indigenous definition of dehydration.

From March 1987 to February 1988, fecal excretion of adenovirus types 40 and 41 and rotavirus serotypes in 194 children (age, 0 to 3 years) from a rural community of Guatemala was monitored. In total, 458 samples taken during 385 episodes of diarrhea and 191 specimens obtained during symptom-free periods were examined by enzyme-linked immunosorbent assay. Fifty-seven children hospitalized because of diarrhea were also studied. Among the rural children, 43 (22.2%) excreted adenovirus types 40 and 41 and 20 (10.3%) shed rotaviruses. Adenovirus types 40 and 41 were associated with 54 (14.0%) illnesses, and rotaviruses were associated with 18 (4.7%) illnesses. Asymptomatic infections with adenovirus types 40 and 41 were documented in nine children and with rotaviruses in two children. Fifteen typeable rotaviruses were identified as serotype 2. In the hospital population, 36 (63.2%) children had viral infections. Rotaviruses were identified in 29 (50.9%) and adenovirus types 40 and 41 were identified in 15 (31.2%) of 48 subjects tested. Dual infections by these viruses were found in eight children. Of 22 typeable strains of rotaviruses, 9 (34.6%) were serotype 1, 12 (46.1%) were serotype 2, and 1 (3.8%) was serotype 3. All the children infected with serotype 2 rotavirus were coinfected with other enteric pathogens, while only three (37.5%) of those infected with rotavirus serotype 1 excreted another pathogen. Adenovirus types 40 and 41 are an important cause of gastroenteritis in both ambulatory and hospitalized Guatemalan children. There seems to be a difference in the pathogenicity among rotavirus serotypes.

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined at admission to the INCAP Clinical Center in eight acutely malnourished Guatemalan children, and again after 14 and 28-30 days of nutritional therapy. While the mean percentage of E-rosettes increased during therapy, the change (from 35.6 +/- 10% to 43.3 +/- 19%) did not reach statistical significance because of the variable response of different subjects. At each time period, however, in vitro incubation with the thymic factor, thymosin fraction 5, significantly increased the percentage of E-rosetting lymphocytes. The presence of thymosin responsive cells in circulation after 1 month of optimal nutritional support indicates that immature T-lymphocytes can persist in circulation in patients with severe malnutrition, even after clinical improvement. Thus, neither the percentage of E-rosettes in peripheral blood nor their response to in vitro incubation with thymosin correlated with anthropometric measures of nutritional status in individual patients. This suggests that other nutritional or nonnutritional factors may be important modulating influences on T-lymphocytes, and that prospective studies with thymic factor administration are warranted.

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.

The concentration in human milk of IgA antibodies against six Salmonella and two Shigella groups was determined in specimens obtained from Swedish and Guatemalan nursing mothers of three different socioeconomic levels. The daily intakes of milk antibodies by their children were also estimated. The results show that the concentrations of specific IgA antibodies in milk vary among the different population groups. There is, however, no difference in daily intake of specific IgA by the children.

The secretory immunoglubulin of the Immunoglobulin A class (SIgA) appears to be the most important of the soluble substances in human milk in terms of protection against diarrheal disease in breastfed infants. Longterm follow-up studies of milk antibodies in human milk have indicated that the concentration of IgA specific antibodies fluctuates during lactation with the most dramatic changes noted among women living in areas where hygienic conditions are poor. Total SIgA concentration and IgA-specific antibodies against Escherichia coli labile toxin (EcLT) Shigella B6 somatic antigen (SB6) and rotaviruses were determined in 20 lactating mothers from a rural area in Guatemala over a 16-week period. The mean concentration of SIgA was highest at the beginning of lactation and reached a plateau at 2-3 weeks postpartum. The levels of specific antibodies against EcLT SB6 and rotaviruses fluctuated in each of the women independently of total SIgA concentration and of one another. In 90% of subjects at least 1 of the specific antibodies reached nondetectable levels at some point in the study. These fluctuations may be related to the presence of homologous antigens in the maternal intestine. It is suggested that the presence of the antigen in the intestine of the mother inhibits the migration of primed IgA committed lymphocytes from the intestine to the mammary gland. This phenomenon has important practical implications. If a lactopositive breastfeeding mother becomes infected by an intestinal pathogen the levels of her milk antibodies will reach very low levels. In turn if her infant is infected by that pathogen there is an increased likelihood that the infection will result in diarrhea.

Ezeject is a plungerless syringe prefilled with lyophilized measles vaccine. Ezeject syringes were compared with standard 3-cc syringes and 10-dose measles vaccine vials in the vaccination of 884 Guatemalan infants 8-23 months of age. Vaccination was performed by experienced vaccinators and by individuals without prior vaccination experience who received 2.5-3 hours of training. The overall seroconversion rate following administration was 96%, regardless of the type of syringe used or of the experience of the vaccinator. No significant adverse events were observed in children vaccinated with the new syringes. Although incomplete emptying was noted in 87% of the Ezeject syringes used, this had no effect on the serologic response to measles vaccine. Aspiration for detection of blood before injection of the vaccine was performed significantly (P less than .001) less frequently with Ezeject than with 3-cc syringes by both experienced and inexperienced personnel. Inexperienced vaccinators administered measles vaccine significantly faster (P less than .001) with Ezeject than with 3-cc syringes, but the times were similar for experienced vaccinators. Ezeject is an acceptable alternative to standard syringes for the administration of measles vaccine. Several design modifications that would improve the handling of the device and eliminate the possibility of its reuse have been suggested.

The concentration of secretory IgA and the levels of IgA specific antibodies against Escherichia coli labile-toxin, Shigella flexneri 6, and rotaviruses were determined in milk samples obtained serially from women during the first 16 weeks postpartum. The mean concentration of secretory IgA followed the expected pattern; the levels of specific antibodies fluctuated in an unpredictable manner and independently of milk secretory IgA content, becoming undetectable in many instances. Under some circumstances, continued breast-feeding may not guarantee continued intake of antibodies against intestinal pathogens by the breast-fed infant.

Human milk contains various defense components, such as bifidus and antistaphylococcal factors, lysozyme, lactoferrin, receptor analogues, and lipids, which have been shown to inhibit microbial adhesion to host cells, function, proliferation and/or expression in vitro.1–5 The biologic significance of these substances in the gastrointestinal tract of the breast-fed infant needs further elucidation. In addition, human colostrum and milk contain large numbers of cells involved in immune reactions, such as macrophages, neutrophiles, B- and T- lymphocytes, and immunoglobulins G, M, and A,6–9 The secretory immunoglobulin A (SIgA), is formed by two IgA monomers, a joining (J) chain, and a secretory component (SC); this particular arrangement makes the molecule of SIgA resistant to enzymatic degradation and, therefore, functional in the gastrointestinal tract.10

During July 1985 to June 1986, fecal excretion of Cryptosporidium oocysts was determined prospectively in a cohort of 130 infants, aged 0 to 11 months, living in a marginal urban area of Guatemala City, Guatemala. A total of 1,280 stool specimens were examined; 158 of them were collected during episodes of diarrhea, and 1,122 were collected during symptom-free periods, every 2 to 3 weeks, from every child. Of the children, 20 (15.4%) excreted Cryptosporidium oocysts during the observation period. Of the diarrheal episodes, 13 (8.3%) were associated with Cryptosporidium sp. Of the control specimens, seven (0.6%) were positive for oocysts. Most of the infections were documented during the months of February to May, at the end of the dry season. Cryptosporidium infections are very common among Guatemalan infants and are an important cause of diarrhea and weight loss. The introduction of liquid or solid foods in the diets of the children, the presence of domestic animals (dogs, cats, or poultry), and the absence of toilet facilities in the house seem to be important risk factors for infection; also, deficient nutritional status may predispose the infected child to Cryptosporidium-associated illness.

A prospective study to assess whether milk IgA antibodies against Escherichia coli heat labile-toxin protect breast-fed children against labile toxin-induced gastroenteritis was carried out among infants of a marginal urban area in Guatemala. One hundred and thirty children were kept under surveillance for diarrhea by periodic home visits. Stool specimens were collected from each child routinely every 2-3 weeks and during diarrheal episodes, to study the excretion of labile toxin-producing Escherichia coli. Milk samples from the children's mothers were obtained concomitantly with the fecal specimens of the infants to be analyzed for anti-labile toxin antibodies. Twenty infections by heat-labile toxin-producing Escherichia coli as a sole agent were documented among breast-fed infants. Nine of these infections resulted in gastroenteritis, while the remaining 11 were asymptomatic. At the time of infection children who became sick were ingesting breast milk with significantly (p = 0.028) lower titers of antilabile toxin IgA than those who remained healthy. Only one of the 8 infected children receiving breast milk with high titers (greater than or equal to 256) of anti labile toxin IgA developed diarrhea, compared to 8 of the 12 subjects being fed milk with low titers (less than or equal to 64) (p = 0.025). This is the first report documenting protection by IgA antibodies in milk against labile toxin-induced gastroenteritis in infected breast-fed infants.

Human milk contains antibodies of the secretory IgA (SIgA) type directed against a variety of enterobacteria, viruses and food proteins. The appearance of these milk antibodies with specificity against antigens of intestinal origin is difficult to explain, unless there is a close link between the immune response in the mammary gland and intestinal exposure. There is some evidence which suggests that antigens in the intestine may stimulate lymphoid cells from the Peyer’s patches which are committed to IgA synthesis to home to various exocrine glands, including the mammary gland. As a consequence of the enteromammaric Zink, the breast-fed baby is supplied with SIgA milk antibodies against micro-organisms which are common in the environment. These antibodies have the capacity to prevent bacterial attachment to mucous membranes which is the initial step in most infections. Determination of milk antibodies also provides epidemiological information concerning intestinal pathogens and can be used to reflect mucosal immunity in response to various vaccinations.

This study investigates the presence of antibodies against food products in milk samples from 30 Guatemalan women of 3 different socioeconomic status: 10 rural poor, 10 urban poor, and 10 urban privileged. The 3 groups had varied dietary habits. Both the rural and urban poor mothers do not consume cow's milk. Black beans are consumed more often by the urban groups while soy bean products are consumed by both rural and urban poor regularly. Milk samples were collected from the mothers. The volume of milk produced in a 24-hour period was estimated by weighing the children before and after every meal. The enzyme-linked immunosorbent assay (ELISA) described by Sohe-Akerlund et.al. was used in quantitating milk secretory immunoglobulin A (SIgA). A modification of the ELISA method was used to determine levels of specific IgA antibodies directed against cow's milk, black beans and soybeans. The Wilcoxon rank sum test was used in statistical analysis. Comparable amounts of SIgA were produced by the 3 groups of mothers in a 24-hour period (p0.1). The urban privileged mothers exhibited significantly higher antibody levels against cow's milk (p0.01) and black beans (p0.05) compared to the other 2 groups. There were no differences in the level of anti-soybean antibodies among the 3 groups. The notion that antibodies found in the breast milk reflect the mother's intestinal antigenic experience is supported by this study. It has been suggested that anti-food protein antibodies contribute in the prevention of allergies. If so, cow's milk fed among the rural and urban poor children may be expected to produce negative reactions. This negative reaction can be prevented by feeding the mother, before delivery, cow's milk products to induce them to produce milk antibodies against cow's milk.

We studied the milk content of secretory IgA (SIgA) and of specific IgA antibodies to E. coli in relation to volume, in 24 h samples from mothers belonging to different socio-economic groups and living under different ecologic conditions in Ethiopia, Guatemala and Sweden. There were no statistically significant differences in the daily output of milk SIgA among the population groups investigated at different times after onset of lactation. There was, however, a certain trend towards lower SIgA levels among the Guatemalan poor women, compared to the corresponding privileged one (Tables 2 and 3). Three days after delivery the underprivileged Ethiopian mothers showed significantly lower antibody levels than the privileged Ethiopian. These differences were no longer seen when the values were corrected for differences in volume (Table 5). One month after delivery, the levels of SIgA antibodies in milk from Swedish women and Guatemalan privileged women, against a pool of eight E. coli somatic antigens were comparable; these two groups of mothers had significantly higher antibody levels than the Guatemalan rural and urban ones (Table 4). The same pattern was observed after correction for differences in 24 h volumes (Table 5). At 3 months after delivery, the Guatemalan urban privileged women, again showed higher levels and daily output of antibodies against the E. coli antigens than the urban poor and rural mothers (Tables 4 and 5). The milk samples taken from a population where malnutrition is evident, i.e., mothers from Santa Maria Cauque, did not show any changes in the levels of SIgA and the anti-E. coli antibodies 3, 6, 9 months after initiation of lactation. The data presented here provide evidence that chronically malnourished mothers are able to produce SIgA and transfer it to their offspring via breast milk. Furthermore, they do so in quantities that are comparable to those observed in well-nourished populations. There was a wide range of concentrations and daily output of SIgA and of specific antibodies in all groups, suggesting that some of the infants get less than others. The observed differences in levels of antibodies against E. coli may be explained by differences in exposure to E. coli strains of the eight serogroups studied here. The possibility of a deficiency in the SIgA antibody response in the undernourished mothers still remains unanswered.

Le probleme discute est celui de l'utilisation d'un filtrat de selles humaines pour la determination de la dose infectieuse d'un rotavirus, sous l'angle de l'innocuite pour les volontaires. Les regles d'innocuite definies il y a plus de 20 ans ne sont pas suffisantes aujourd'hui et d'autres criteres sont necessaires

The causes of fetal growth retardation and premature delivery are not well defined. Although diet, smoking, maternal weight and height, and social class can be correlated with the size of the fetus, the relative contribution of other factors to fetal growth has not been clarified. Among such factors in developing countries, the highly prevalent infectious diseases occupy a prominent place. This report summarizes studies of the frequency of infections in pregnant women and discusses their possible influence on intrauterine growth. PATIENTS AND METHODS The present data were derived from a long-term prospective investigation of the interactions of nutrition and infection and the outcome of pregnancy in a highland Indian village. 1-3 Since 1972, all women of child-bearing age have been visited every month and interviewed regarding their menses. A urine gonadotrophin test was used for the diagnosis of pregnancy in women reporting amenorrhea. Each pregnant woman underwent anthropometric and obstetric