CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population.

The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

Patologías del niño inmigrante en la Unidad de Cuidados Intensivos: actualización / Pathologies of the immigrant child in the Intensive Care Unit: update

Resumen: Cada vez es más frecuente la atención médica en la Unidad de Cuidados Intensivos (UCI) de niños o adolescentes inmigrantes como también de aquellos nacidos en nuestro país con padres en tal condición. Esto ha ocasionado, en la actualidad, que el equipo de salud se deba enfrentar con problemas diagnósticos derivados del escaso conocimiento de condiciones genéticas propias de esta población y/o el desarrollo de diversas patologías infrecuentes en nuestro país, algunas resultantes de su condi ción sanitaria. En esta revisión se abordan diversos aspectos de la patología hematológica, infecciosa, parasitaria, respiratoria y cardiovascular, todos tópicos relevantes de conocer durante su estadía en la UCI. Es un deber del equipo de salud actualizarse sobre patologías de baja prevalencia en nuestro país, algunas de ellas muy poco conocidas hasta hace una década, pero que, actualmente, están cada vez más presentes en las UCI del sistema de salud público chileno.

Abstract: It is increasingly common to provide medical care in the Intensive Care Unit (ICU) for immigrant children and adolescents as well as those born in Chile with parents in such condition. Currently, this has caused that the health team has to face diverse infrequent pathologies in our country and/ or diagnostic problems derive from the poor knowledge of genetic conditions of this population, some resulting from their health conditions. This review addresses several aspects of hematological, infectious, parasitic, respiratory, and cardiovascular pathologies, all relevant topics to know during their stay in the ICU. It is a duty of the health team to be updated on pathologies of low prevalence in our country, some of them very little known until a decade ago, but which are currently increasingly present in the ICUs of the Chilean public health system.

Association of serious infections with pemphigus and pemphigoid: analysis of the Nationwide Inpatient Sample.

BACKGROUND: Pemphigus and pemphigoid are blistering disorders associated with barrier disruption, immune dysregulation and use of immunosuppressing systemic therapy, all of which may predispose towards serious infections. OBJECTIVES: To determine whether pemphigus and pemphigoid are associated with increased likelihood of serious infections and the impact of such infections on mortality and cost of care. METHODS: We analysed data from the 2002 to 2012 Nationwide Inpatient Sample, including a representative 20% sample of all hospitalizations in the US (total n = 72 108 077 adults). RESULTS: Overall, 54.6% (95% CI: 53.6-55.6%) and 50.4% (49.0-51.8%) of inpatients with either pemphigoid or pemphigus had a diagnosis of serious infection, respectively, compared with 25.4% (25.2-25.6%) in those without either diagnosis. In multivariable logistic regression models controlling for gender, age, race/ethnicity and insurance status, pemphigoid or pemphigus was associated with 26 or 21 of 48 infections examined, respectively. In particular, both pemphigoid and pemphigus were associated with higher odds of infections of the skin, bones, respiratory, gastrointestinal, genitourinary and central nervous system, septicaemia and antibiotic-resistant infections. Pemphigus was also associated with aspergillus, pharyngitis and Pneumocystis Carinii pneumonia. Associations of any serious infection in both pemphigoid and pemphigus patients were older age, non-White race, lower median household income, government or no insurance, higher number of chronic conditions, and those with a diagnosis of Cushing's syndrome, diabetes, cancer or autoimmune disease. The diagnosis of any serious infection vs. no infection was associated with increased inpatient mortality and costs in both pemphigoid (mortality: 7.85% vs. 2.84%; cost: $16 115 vs. $10 653) and pemphigus (mortality: 6.78% vs. 1.88%; cost: $17 707 vs. $11 545) inpatients (P < 0.0001 for all). CONCLUSIONS: Adults with pemphigus or pemphigoid had increased cutaneous, respiratory, multi-organ and systemic infections, which were associated with considerable inpatient mortality and cost burden. Moreover, there were significant clinical and healthcare disparities with respect to infections in patients with pemphigus or pemphigoid.

[Mortality of immigrants in Tuscany Region (Central Italy), 1997-2013]. / Mortalità della popolazione immigrata in Toscana dal 1997 al 2013.

OBJECTIVES: to evaluate mortality in immigrants dwelling in Tuscany Region (Central Italy) compared to mortality data relating to the Italian population residing in the same region. DESIGN: cross-sectional descriptive mortality study relying on a unique data source, i.e., the Regional Mortality Registry of Tuscany, for the period 1997-2013. SETTING AND PARTICIPANTS: in the analysis, immigrants residing in Tuscany were included; Italian residing in the same region were the comparison population. Immigrants were divided into two categories: immigrants from Countries at High Migration Rates (CHMRs) and immigrants from Developed Countries (DCs). MAIN OUTCOME MEASURES: proportional general and cause-specific mortality by age and gender for the period 1997-2013; trends of standardized truncated (age 20-64) mortality rates for the Italian population, and for immigrants from CHMRs and from DCs for the period 2002-2013; standardized mortality ratios (SMRs) in people from CHMRs with confidence interval at 95% (95%CI) for all causes and cause-specific mortality. RESULTS: during 1997-2013, 4,681 deaths were recorded among immigrants, 3,005 of which were in immigrants from a CHMR. Both cause-specific and general mortality trends in Italians and in immigrants from DCs are lowering, while general mortality of immigrants from CHMRs seems to have risen in the last 5 years. Mortality of people from CHMRs for all causes, cardiovascular causes, and cancer is permanently lower than Italian population's mortality in the examined period, but the gap seems to progressively reduce. On the other hand, child mortality among immigrants from CHMRs, despite a declining trend, is consistently higher than Italian population's mortality. Following the SMR analysis, the only exceeding cause of mortality in people from CHMRs - compared to the Italian population - is homicide among men (SMR: 3.46; 95%CI 1.55-5.59). CONCLUSIONS: this study updates our knowledge on immigrants' mortality - and, indirectly, on their health status - in Tuscany. The gap between mortality of Italians and immigrants from CHMRs is reducing: this could be partially explained by a successful ongoing integration process. For future analyses, it would be important to obtain more complete data relative to non-resident immigrants' mortality, as their number is constantly increasing.

Infection-related mortality in Hispanic and non-Hispanic children with cancer.

BACKGROUND: Hispanic children with cancer experience poorer survival than their White counterparts. Infection is a known cause of cancer-related mortality; however, little is known about the risk of infection-related death among Hispanic children with cancer. We examine the association of Hispanic ethnicity with infection-related mortality and life-threatening events among children with cancer. PROCEDURE: For a cohort of all pediatric cancer patients diagnosed from 1986 to 2012 and treated at a single tertiary care center, we obtained national death records to determine all-cause mortality and infection-related mortality, as well as intensive care unit (ICU) admissions as a surrogate for life-threatening events. Cox proportional hazard models assessed all-cause mortality and infection-related mortality using ethnicity as the main independent variable. ICU admission rates were modeled using a zero-inflated Poisson regression model. Models were adjusted for gender, diagnosis year, age, residential location, and diagnosis. RESULTS: Of 6,198 patients, 741 (12%) were Hispanic. Mean follow-up was 11 years (SD = 8.04). There were 1,205 deaths, with 193 attributable to infection. Differences in all-cause mortality between Hispanic and non-Hispanic patients did not reach significance (hazard ratio [HR] = 1.14, 95% confidence interval [CI]: 0.96-1.36). However, Hispanic patients were 68% (HR = 1.68, 95% CI: 1.16-2.43) more likely to have an infection-related cause of death. Hispanic ethnicity was statistically associated with a higher rate of ICU admissions (rate ratio = 1.32, 95% CI: 1.12-1.56). CONCLUSION: Hispanic pediatric cancer patients were more likely to have an infection-related death and higher rates of ICU admissions than non-Hispanic patients. Infection may be an overlooked contributor to poorer outcomes among Hispanic patients.

Collaborating with a social housing provider supports a large cohort study of the health effects of housing conditions.

BACKGROUND: Despite the importance of adequate, un-crowded housing as a prerequisite for good health, few large cohort studies have explored the health effects of housing conditions. The Social Housing Outcomes Worth (SHOW) Study was established to assess the relationship between housing conditions and health, particularly between household crowding and infectious diseases. This paper reports on the methods and feasibility of using a large administrative housing database for epidemiological research and the characteristics of the social housing population. METHODS: This prospective open cohort study was established in 2003 in collaboration with Housing New Zealand Corporation which provides housing for approximately 5% of the population. The Study measures health outcomes using linked anonymised hospitalisation and mortality records provided by the New Zealand Ministry of Health. RESULTS: It was possible to match the majority (96%) of applicant and tenant household members with their National Health Index (NHI) number allowing linkage to anonymised coded data on their hospitalisations and mortality. By December 2011, the study population consisted of 11,196 applicants and 196,612 tenants. Half were less than 21 years of age. About two-thirds identified as Maori or Pacific ethnicity. Household incomes were low. Of tenant households, 44% containing one or more smokers compared with 33% for New Zealand as a whole. Exposure to household crowding, as measured by a deficit of one or more bedrooms, was common for applicants (52%) and tenants (38%) compared with New Zealanders as whole (10%). CONCLUSIONS: This project has shown that an administrative housing database can be used to form a large cohort population and successfully link cohort members to their health records in a way that meets confidentiality and ethical requirements. This study also confirms that social housing tenants are a highly deprived population with relatively low incomes and high levels of exposure to household crowding and environmental tobacco smoke.

Dysplasia features of myelodysplastic syndrome in ethnically Chinese people.

OBJECTIVE: It was our aim to study the diagnostic significances of various dysplasia characteristics in myelodysplastic syndrome (MDS). METHODS: We analyzed 160 cases of primary MDS and a control group including 28 cases of paroxysmal nocturnal hemoglobinuria (PNH), 104 cases of idiopathic thrombocytopenic purpura (ITP), 53 cases of non-severe aplastic anemia (NSAA), 40 cases of megaloblastic anemia and 50 cases of infectious and autoimmune diseases. Peripheral blood smears and bone marrow morphology were reviewed. RESULTS: There was no significant difference in the occurrence rates of a variety of dysplasias in three lineages among MDS, megaloblastic anemia and PNH; however, changes in qualities and quantities in three lineages between NSAA and MDS were significantly different. ITP and MDS showed statistical differences in multiple changes in myeloid and erythroid cells. Significant differences also existed in multiple changes in erythroid series and megakaryocytes between infectious and autoimmune diseases and MDS. Morphological abnormalities highly related with MDS included multinucleated erythroblasts, ringed sideroblasts, poikilocytosis and gigantocytes, pseudo-Pelger neutrophils, ring-shaped nucleus, and micromegakaryocytes. CONCLUSIONS: It is difficult to discriminate megaloblastic anemia and PNH from MDS by means of cell morphology. Different dysplasias of MDS have specific diagnostic values.

Chronic disease mortality associated with infectious agents: a comparative cohort study of migrants from the Former Soviet Union in Israel and Germany.

BACKGROUND: Prevalence of infectious diseases in migrant populations has been addressed in numerous studies. However, information is sparse on their mortality due to chronic diseases that are aetiologically associated with an infectious agent. This study investigates mortality related to infectious diseases with a specific focus on cancers of possibly infectious origin in voluntary migrants from the Former Soviet Union residing in Israel and in Germany. METHODS: Both groups of migrants arrived from the Former Soviet Union in their destination countries between 1990 and 2001. Population-based data on migrants in Israel were obtained from the Israel Central Bureau of Statistics. Data for migrants in Germany were obtained from a representative sample of all migrants from the Former Soviet Union in Germany. Cause of death information was available until 2003 for the Israeli cohort and until 2005 for the German cohort. Standardized mortality ratios were calculated relative to the destination country for selected causes of death for which infectious agents may be causally involved. Multivariate Poisson regression was applied to assess differences in mortality by length of residence in the host country. RESULTS: Both in Israel and in Germany these migrants have lower overall mortality than the population in their destination countries. However, they have significantly elevated mortality from viral hepatitis and from stomach and liver cancer when compared to the destination populations. Regression analysis shows that in Israel stomach cancer mortality is significantly higher among migrants at shorter durations of residence when compared to durations of more than nine years. CONCLUSION: Higher mortality from cancers associated with infection and from viral hepatitis among migrants from the Former Soviet Union might result from higher prevalence of infections which were acquired in earlier years of life. The results highlight new challenges posed by diseases of infectious origin in migrants and call attention to the link between communicable and non-communicable diseases.

The risk of cancer following hospitalization for infection in infancy: a population-based cohort study.

BACKGROUND: The relation between infections in infancy and subsequent cancer risk in children and young adults is controversial. Our aim was to examine this association in the Jerusalem Perinatal Study, a population-based cohort comprising all offspring from western Jerusalem and surroundings born from 1964 to 1976. METHODS: Identity numbers of non-malformed singletons with recorded data about hospital admission in the 1st year of life (n = 24,554) were linked to the Population and Cancer Registries. Person-year incidence rates were calculated for the exposed (admitted for infection) and nonexposed (not admitted for infection) groups from birth to date of cancer diagnosis, death, or December 31, 2004. We used Cox proportional hazards models to adjust for covariates associated with hospitalization. RESULTS: The median follow-up was 36 years. Cancer developed in 283 individuals. Hospitalization for infection was not associated with overall cancer risk [risk ratio (RR), 0.88; 95% confidence interval (95% CI), 0.56-1.37]. The incidence rate for non-Hodgkin's lymphoma was higher in the exposed compared with the nonexposed group (RR, 3.46; 95% CI, 1.38-8.68), remaining unchanged after controlling for birth weight, gender, and maternal education. Leukemia risk was not significantly associated (RR, 0.44; 95% CI, 0.06-3.24) with hospitalization for infection. CONCLUSIONS: Hospital admission in the 1st year of life due to infection is associated with an increased risk of non-Hodgkin's lymphoma. This is consistent with observations that mild immunodeficiencies predispose to lymphoma. Survival of infants with subtle immune defects, who may have previously succumbed to their infection, may contribute to the increased incidence of non-Hodgkin's lymphoma observed over the last 50 years.

Illness, injury, and disability among Shiwiar forager-horticulturalists: implications of health-risk buffering for the evolution of human life history.

Human life history is distinguished by long lifespan, delayed reproduction, intergenerational asymmetric benefit transfers from adults to juveniles and between adults, and a large brain able to engage in unprecedented levels of learning, reasoning, and insight. The evolution of these traits depends on relatively low human mortality. Understanding why humans have low mortality is therefore critical for understanding the evolution of key human traits. One explanation is that the evolution of food provisioning during periods of health crisis reduced mortality. This hypothesis turns on health risk having posed a significant adaptive problem that could be effectively buffered by healthcare provisioning. Unfortunately, the frequency, duration, and fitness effects of temporary disability are difficult to estimate based on osteological evidence alone, and systematic ethno-biological research on these issues among extant small-scale societies with little access to Western medical care is lacking. Here I present data on 678 injuries and illnesses suffered by 40 Shiwiar forager-horticulturalists, based on physical evidence and informant reports. A subsample of 17 individuals provided data on incidence and duration of disability for 215 pathological incidents. Results indicate that injury and illness occur frequently across the lifespan. Most living individuals have suffered temporarily disabling health crises likely to have been lethal without provisioning. The fitness effects of surviving these episodes are high, suggesting that the Shiwiar population structure and lifeway are dependent on infrequent extended provisioning to temporarily disabled individuals, and that provisioning of aid during healthcare crises effectively lowers mortality in this small-scale society.

Contribution of major diseases to disparities in mortality.

BACKGROUND: Mortality from all causes is higher for persons with fewer years of education and for blacks, but it is unknown which diseases contribute most to these disparities. METHODS: We estimated cause-specific risks of death from data from the National Health Interview Survey conducted from 1986 through 1994 and from linked vital statistics. Using these risk estimates, we calculated potential years of life lost and potential gains in life expectancy related to specific causes, with stratification according to education level and race. RESULTS: Persons without a high-school education lost 12.8 potential life-years per person in the population, as compared with 3.6 for persons who graduated from high school (ratio, 3.5; P<0.001). Ischemic heart disease contributed most (11.7 percent) to the difference according to education in potential life-years lost (with all cardiovascular diseases accounting for 35.3 percent). All cancers accounted for 26.5 percent, including 7.7 percent due to lung cancer; other lung diseases and pneumonia contributed 10.1 percent of the total, whereas human immunodeficiency virus (HIV) disease accounted for none of the difference according to education. The pattern of disparities according to level of income was similar to that according to level of education. Blacks and whites lost 7.0 and 5.2 potential life-years per person, respectively, as a result of deaths from any cause (ratio, 1.35; P<0.001). Cardiovascular diseases accounted for one third of this disparity, in large part because of hypertension (15.0 percent); HIV disease (11.2 percent) contributed almost as much as ischemic heart disease (5.5 percent), stroke (2.8 percent), and cancer (3.4 percent) combined; trauma and diabetes mellitus accounted for 10.7 percent and 8.5 percent, respectively. CONCLUSIONS: Although many conditions contribute to socioeconomic and racial disparities in potential life-years lost, a few conditions account for most of these disparities - smoking-related diseases in the case of mortality among persons with fewer years of education, and hypertension, HIV, diabetes mellitus, and trauma in the case of mortality among black persons. These findings have important implications for targeting efforts to reduce existing disparities in mortality rates.

Mot luuk problems in Northeast Thailand: why women's own health concerns matter as much as disease rates.

In this paper, we consider women's illness experiences, above and beyond the presence of clinically identifiable disease. In Northeast Thailand, epidemiological data suggest that the prevalence of major women's reproductive tract infections is relatively low and not a cause for significant public health attention. Conversely, we found that self-reported rates of gynecological complaints are high and a significant women's health concern in rural Northeast villages. Women's embodied experiences and interpretations of these complaints affect their lives dramatically. Moreover, women's responses to gynecological problems (regardless of diagnosed morbidity) constitute an important health issue in their own right. In this regard, we document the dangers of women's self-treatment practices that rely largely on small doses of medically inappropriate antibiotics, the manner in which family life and sexual relations are disrupted by fears that gynecological problems will progress to cervical cancer, health care seeking patterns and expectations from health staff, and most importantly, how women's concerns about the seriousness of recurrent ailments result in substantial suffering. This study demonstrates why attention to women's own health concerns is as important to address in health programs as rates of disease, and why common gynecological problems and work-related complaints are important to take seriously rather than dismiss as psychological or routine and expected. We argue that there is a strong need to conduct ethnographic research on women's health problems as a complement to, and not merely a support for, epidemiological research. An evidence-based approach to health policy needs to be accompanied by a more humanistic approach to understanding health care needs.

Alteraçöes anatomopatológicas da mucosa gástrica associadas à infecçäo pelo Helicobacter Pylori / Alteraçoes anatomopatologicas of the gastrica mucosa associates infecçao for the Helicobacter pylori

O Helicobacter pylori é considerado o patógeno humano mais prevalente no mundo, e é a causa mais frequente de gastrite crônica ativa. Sua relaçäo com a etiopatogenia das doenças inflamatórias gastroduodenais e, possivelmente, do carcinoma gástrico e do linfoma MALT, tem justificado o interesse no estudo das diversas alteraçöes anatomopatológicas na mucosa gástrica encontradas nesta infecçäo. Para avaliar as alteraçöes anatomopatológicas associadas à infecçäo pelo Helicobacter pylori, foram analisados fragmentos de biópsia de corpo e de antro gástrico de 64 indivíduos portadores da infecçäo (GRUPO I), e de 20 indivíduos com teste da erease a pesquisa histológica negativas para Helicobacter pylori...