Acute respiratory infections in children living in two low income communities of Rio de Janeiro, Brazil

Community studies of non-hospitalized children are essential to obtain a more thorough understanding of acute respiratory infections (ARI) and provide important information for public health authorities. This study identified a total ARI incidence rate (IR) of 4.5 per 100 child-weeks at risk and 0.78 for lower respiratory tract infections (LRI). Disease duration averaged less than one week and produced a total time ill with ARI of 5.8% and for LRI 1.2%. No clear seasonal variation was observed, the sex-specific IR showed a higher proportion of boys becoming ill with ARI and LRI and the peak age-specific IR occurred in infants of 6-11 months. Correlation with risk factors of the child (breastfeeding, vaccination, diarrheal disease, undernourishment) and the environment (crowding, living conditions, maternal age and education) showed marginal increases in the rate ratios, making it difficult to propose clear-cuts targets for action to lower the ARI and LRI morbidity. The importance of an integral maternal-child health care program and public education in the early recognition of LRI is discussed.

The Barcelona Forum: on decentralized governance and conflict prevention 6-8 july 2009

The Barcelona Forum aimed to generate both a theoretical and practical discussion on decentralized governance and its capacity to promote peace, prevent conflict, advance human security and ensure greater governmental accountability. The Forum intended to review the theoretical strength of decentralization as a political tool and discuss how it can be properly implemented. Eight case studies were selected to be covered during the two days in order to draw conclusions and offer proposals for the future implementation of decentralization. The case of Catalonia and the decentralized experience of Spain was given special attention, as an example of successful decentralization. The other cases presented achievements and challenges and prompted discussions on both the validity and universality of decentralization as a way to promote and preserve peace. Topics such as ethnic and territorial divisions, democratic accountability, financial decentralization and distribution, resource sharing, and external implementation of decentralization through peace processes were discussed.

Trypanosoma cruzi in the anal glands of urban opossums: I- isolation and experimental infections

Opossums (Didelphis marsupialis) captured in intensely urbanized areas of the city of Caracas, Venezuela, were found infected with Trypanosoma cruzi. The developmental cycle of trypomastigote-epimastigote-metacyclic infective trypomastigote, usually occurring in the intestine of the triatomine vector, was taking place in the anal odoriferous glands of the opossums. Material from the glands, inoculated in young, healthy opossums and white mice by different routes, subcutaneously, intraperitoneally, orally, and into the eye, induced T. cruzi infections in all animals. Parasitemia, invasion of cardiac and skeletal muscle, and intracellular multiplication of amastigotes were observed. Inoculation of metacyclics from anal glands, cultured in LIT medium, gave equivalent results. All opossums survived; all mice died. Excreta of opossums may thus transmit Chagas' disease by contamination, even in urban areas where insect vectors are not present.

Physicians' attitudes towards prevention: importance of intervention-specific barriers and physicians' health habits.

BACKGROUND: Several studies have explored physicians' attitudes towards prevention and barriers to the delivery of preventive health interventions. However, the relative importance of these previously identified barriers, both in general terms and in the context of a number of specific preventive interventions, has not been identified. Certain barriers may only pertain to a subset of preventive interventions. OBJECTIVES: We aimed to determine the relative importance of identified barriers to preventive interventions and to explore the association between physicians' characteristics and their attitudes towards prevention. METHODS: We conducted a cross-sectional survey of 496 of the 686 (72.3% response rate) generalist physicians from three Swiss cantons through a questionnaire asking physicians to rate the general importance of eight preventive health strategies and the relative importance of seven commonly cited barriers in relation to each specific preventive health strategy. RESULTS: The proportion of physicians rating each preventive intervention as being important varied from 76% for colorectal cancer screening to 100% for blood pressure control. Lack of time and lack of patient interest were generally considered to be important barriers by 41% and 44% of physicians, respectively, but the importance of these two barriers tended to be specifically higher for counselling-based interventions. Lack of training was most notably a barrier to counselling about alcohol and nutrition. Four characteristics of physicians predicted negative attitudes toward alcohol and smoking counselling: consumption of more than three alcoholic drinks per day [odds ratio (OR) = 8.4], sedentary lifestyle (OR = 3.4), lack of national certification (OR = 2.2) and lack of awareness of their own blood pressure (OR = 2.0). CONCLUSIONS: The relative importance of specific barriers varies across preventive interventions. This points to a need for tailored practice interventions targeting the specific barriers that impede a given preventive service. The negative influence of physicians' own health behaviours indicates a need for associated population-based interventions that reduce the prevalence of high-risk behaviours in the population as a whole.

Histopathological study of experimental and natural infections by Trypanosoma cruzi in Didelphis marsupialis

Didelphis marsupialis, the most important sylvatic reservoir of Trypanosoma cruzi, can also maintain in their anal scent glands the multiplicative forms only described in the intestinal tract of triatomine bugs. A study of 21 experimentally and 10 naturally infected opossums with T. cruzi was undertaken in order to establish the histopathological pattern under different conditions. Our results showed that the inflammation was predominantly lymphomacrophagic and more severe in the naturally infected animals but never as intense as those described in Chagas' disease or in other animal models. The parasitism in both groups was always mild with very scarce amastigote nests in the tissues. In the experimentally infected animals, the inflammation was directly related to the presence of amastigotes nests. Four 24 days-old animals, still in embryonic stage, showed multiple amastigotes nests and moderate inflammatory reactions, but even so they survived longer and presented less severe lesions than experimentally infected adult mice. Parasites were found in smooth, cardiac and/or predominantly striated muscles, as well as in nerve cells. Differing from the experimentally infected opossums parasitism in the naturally infected animals predominated in the heart, esophagus and stomach. Parasitism of the scent glands did not affect the histopathological pattern observed in extraglandular tissues.

High number of CD56(bright) NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections.

BACKGROUND: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. RESULTS: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. CONCLUSIONS: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this « rare » HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts.

Ganciclovir Exposure under a 450 mg Daily Dosage of Valganciclovir for the Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients.

Background: It is suggested that a low dose of valganciclovir can be equally effective than a standard dose for cytomegalovirus (CMV) prophylaxis after kidney transplantation. The aim of our study was to determine the ganciclovir exposure observed under a routine daily dosage of 450 mg valganciclovir in kidney transplant recipients with a wide range of renal function. Methods: In this prospective study, kidney transplant recipients with a GFR MDRD above 25 mL/min at risk for CMV (donor or recipient seropositive for CMV) received a dose of valganciclovir (450 mg daily) prophylaxis for 3 months. Ganciclovir levels at trough (Ctrough) and at peak (C3h) were measured monthly. Ganciclovir exposure (AUC0-24) was estimated using Bayesian non-linear mixed-effect modelling (NONMEM) and compared between 3 groups of patients according to their kidney function: GFRMDRD 26-39 mL/min (Group 1), GFRMDRD 40-59 mL/min (Group 2) and GFRMDRD 60-90 mL/min (Group 3). CMV DNAemia was assessed during and after prophylaxis using PCR. Results: Thirty-six patients received 450 mg daily of valganciclovir for 3 months. Median ganciclovir C3h was 3.9 mg/L (range: 1.3-7.1) and Ctrough was 0.4 mg/L (range 0.1-2.7). Median (range) AUC0-24 of ganciclovir was 59.3 mg.h/L (39.0-85.3) in Group 1 patients, 35.8 mg.h/L (24.9-55.8) in Group 2 patients and 29.6 mg.h/L (22.0- 43.2) in Group 3 patients (p<0.001). Anemia was more common in Group 1 patients compared to patients on the other groups (p=0.01). No differences in other adverse events according to ganciclovir exposure were observed. CMV DNAemia was not detected during prophylaxis. After discontinuing prophylaxis, CMV DNAemia was seen in 8/34 patients (23.5%) and 4/36 patients (11%) developed CMV disease. Conclusion: A routine dosage of valganciclovir achieved plasma levels of ganciclovir in patients with GFR>60 mL/min similar to those previously reported using oral ganciclovir. A daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.

Eligibility for statin therapy in primary prevention: discrepancies using different guidelines in a population-based study in Switzerland

Introduction: Recommendations for statin use for primary prevention of coronary heart disease (CHD) are based on estimation of the 10-year CHD risk. We compared the 10-year CHD risk assessments and eligibility percentages for statin therapy using three scoring algorithms currently used in Switzerland. Methods: We studied 5683 women and men, aged 35-75, without overt cardiovascular disease (CVD), in a population-based study in Lausanne, Switzerland. We compared the 10-year CHD risk using three scoring schemes, i.e., the Framingham risk score (FRS) from the U.S. National Cholesterol Education Program's Adult Treatment Panel III (ATP III), the PROCAM scoring scheme from the International Atherosclerosis Society (IAS), and the European risk SCORE for low-risk countries, without and with extrapolation to 60 years as recommended by the European Society of Cardiology guidelines (ESC). With FRS and PROCAM, high-risk was defined as a 10-year risk of fatal or non-fatal CHD >20% and a 10-year risk of fatal CVD >= 5% with SCORE. We compared the proportions of high-risk participants and eligibility for statin use according to these three schemes. For each guideline, we estimated the impact of increased statin use from current partial compliance to full compliance on potential CHD deaths averted over 10 years, using a success proportion of 27% for statins. Results: Participants classified at high-risk (both genders) were 5.8% according to FRS and 3.0% to the PROCAM, whereas the European risk SCORE classified 12.5% at high-risk (15.4% with extrapolation to 60 years). For the primary prevention of CHD, 18.5% of participants were eligible for statin therapy using ATP III, 16.6% using IAS, and 10.3% using ESC (13.0% with extrapolation) because ESC guidelines recommend statin therapy only in high-risk subjects. In comparison with IAS, agreement to identify eligible adults for statins was good with ATP III, but moderate with ESC (Figure). Using a population perspective, a full compliance with ATP III guidelines would reduce up to 17.9% of the 24'310 CHD deaths expected over 10 years in Switzerland, 17.3% with IAS and 10.8% with ESC (11.5% with extrapolation). Conclusion: Full compliance with guidelines for statin therapy would result in substantial health benefits, but proportions of high-risk adults and eligible adults for statin use varied substantially depending on the scoring systems and corresponding guidelines used for estimating CHD risk in Switzerland.

Infections and functional impairment in nursing home residents: a reciprocal relationship.

OBJECTIVES: To determine the relationship between infections and functional impairment in nursing home residents. DESIGN: Prospective cohort study (follow-up period, 6 months). SETTING: Thirty-nine nursing homes in western Switzerland. PARTICIPANTS: A total of 1,324 residents aged 65 and older (mean age 85.7; 76.6% female) who agreed to participate, or their proxies, by oral informed consent. MEASUREMENTS: Functional status measured every 3 months. Two different outcomes were used: (a) functional decline defined as death or decreased function at follow-up and (b) functional status score using a standardized measure. RESULTS: At the end of follow-up, mortality was 14.6%, not different for those with and without infection (16.2% vs 13.1%, P=.11). During both 3-month periods, subjects with infection had higher odds of functional decline, even after adjustment for baseline characteristics and occurrence of a new illness (adjusted odds ratio (AOR)=1.6, 95% confidence interval (CI)=1.2-2.2, P=.002, and AOR=1.5, 95% CI=1.1-2.0, P=.008, respectively). The odds of decline increased in a stepwise fashion in patients with zero, one, and two or more infections. The analyses predicting functional status score (restricted to subjects who survived) gave similar results. A survival analysis predicting time to first infection confirmed a stepwise greater likelihood of infection in subjects with moderate and severe impairment at baseline than in subjects with no or mild functional impairment at baseline. CONCLUSION: Infections appear to be both a cause and a consequence of functional impairment in nursing home residents. Further studies should be undertaken to investigate whether effective infection control programs can also contribute to preventing functional decline, an important component of these residents' quality of life.

Persistent Infections by Leishmania (Viannia) braziliensis

Here we review the phenomenon of persistency in Leishmania (Viannia) braziliensis infections. In other Leishmania species where appropriate animal models exist, considerable advances in the understanding of basic immunologic mechanisms of persistency have been made; for a review see Aebisher (1994). On the contrary, the evidences of persistence in infections with L. braziliensis rest on studies of human clinical cases many of which we summarized and discussed in this work

Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

BACKGROUND: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. METHODS: We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. RESULTS: As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab. CONCLUSIONS: Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)