Genetic Influences on Incidence and Case-Fatality of Infectious Disease

BACKGROUND: Family, twin and adoption studies suggest that genetic susceptibility contributes to familial aggregation of infectious diseases or to death from infections. We estimated genetic and shared environmental influences separately on the risk of acquiring an infection (incidence) and on dying from it (case fatality). METHODS: Genetic influences were estimated by the association between rates of hospitalization for infections and between case-fatality rates of adoptees and their biological full- and half- siblings. Familial environmental influences were investigated in adoptees and their adoptive siblings. Among 14,425 non-familial adoptions, granted in Denmark during the period 1924-47, we selected 1,603 adoptees, who had been hospitalized for infections and/or died with infection between 1977 and 1993. Their siblings were considered predisposed to infection, and compared with non-predisposed siblings of randomly selected 1,348 adoptees alive in 1993 and not hospitalized for infections in the observation period. The risk ratios presented were based on a Cox regression model. RESULTS: Among 9971 identified siblings, 2829 had been hospitalised for infections. The risk of infectious disease was increased among predisposed compared with non-predisposed in both biological (1.18; 95% confidence limits 1.03-1.36) and adoptive siblings (1.23; 0.98-1.53). The risk of a fatal outcome of the infections was strongly increased (9.36; 2.94-29.8) in biological full siblings, but such associations were not observed for the biological half siblings or for the adoptive siblings. CONCLUSION: Risk of getting infections appears to be weakly influenced by both genetically determined susceptibility to infection and by family environment, whereas there appears to be a strong non-additive genetic influence on risk of fatal outcome

HTLV-1 and HIV-2 Infection Are Associated with Increased Mortality in a Rural West African Community

BACKGROUND: Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau. METHODS: In 1990, 1997 and 2007, adult residents (aged ≥15 years) were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR), comparing retrovirus-infected versus uninfected people. RESULTS: A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0-20.3). The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9) for HIV-1, 4.1 (3.4-5.0) for HIV-2, 3.6 (2.9-4.6) for HTLV-1, and 1.6 (1.5-1.8) for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years) to 12.7 in the youngest (15-29 years). The HR for HIV-2 infection varied from 1.2 (oldest) to 9.1 (youngest), and for HTLV-1 infection from 1.2 (oldest) to 3.8 (youngest). CONCLUSIONS: HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

Traqueobroncomegalia (síndrome de Mounier-Kuhn): relato de caso e revisão da literatura Tracheobronchomegaly (Mounier-Kuhn syndrome): case report and review of the literature

A traqueobroncomegalia é uma rara entidade de etiologia incerta, caracterizada por dilatação marcante da traquéia e brônquios principais, bronquiectasias e infecções recorrentes do trato respiratório inferior. Sua apresentação clínica é inespecífica, sendo o diagnóstico realizado por métodos de imagem. Relata-se, neste trabalho, um caso de tal enfermidade, cujo diagnóstico confirmou-se por radiografia simples do tórax e por tomografia computadorizada.<br>Tracheobronchomegaly is a rare condition of uncertain etiology characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent respiratory tract infections. Clinical presentation is nonspecific and the diagnosis is usually made by imaging methods. We report a case of a patient with tracheobronchomegaly. Diagnosis was confirmed by plain x-ray films and computed tomography of the chest

Vaccination coverage and factors associated with adherence to the vaccination schedule in young children of a rural area in Burkina Faso

Background: Vaccination is an important tool for reducing infectious disease morbidity and mortality. In the past, less than 80% of children 12–23 months of age were fully immunized in Burkina Faso. Objectives: To describe coverage and assess factors associated with adherence to the vaccination schedule in rural area Burkina Faso. Methods: The study population was extracted from the Nouna Health and Demographic surveillance system cohort. Data from four rounds of interviews conducted between November 2012 and June 2014 were considered. This study included 4016 children aged 12–23 months. We assessed the effects of several background factors, including sex, factors reflecting access to health care (residence, place of birth), and maternal factors (age, education, marital status), on being fully immunized defined as having received Bacillus Calmette–Guérin (BCG), three doses of diphtheria–tetanus–pertussis and oral polio vaccine, and measles vaccine by 12 months of age. The associations were studied using binomial regression to derive prevalence ratios (PRs) in univariate and multivariate regression models. Results: The full vaccination coverage increased significantly over time (72% in 2012, 79% in 2013, and 81% in 2014, p = 0.003), and the coverage was significantly lower in urban than in rural areas (PR 0.84; 0.80–0.89). Vaccination coverage was neither influenced by sex nor influenced by place of birth or by maternal factors. Conclusion: The study documented a further improvement in full vaccination coverage in Burkina Faso in recent years and better vaccination coverage in rural than in urban areas. The organization of healthcare systems with systematic outreach activities in the rural areas may explain the difference between rural and urban areas