An Exploration of the Spatiotemporal and Demographic Patterns of Ebola Virus Disease Epidemic in West Africa Using Open Access Data Sources.

The purpose of this study was to investigate the utility of exploratory analytical techniques using publically available data in informing interventions in case of infectious diseases outbreaks. More exactly spatiotemporal and multivariate methods were used to characterize the dynamics of the Ebola Virus Disease (EVD) epidemic in West Africa, and propose plausible relationships with demographic/social risk factors. The analysis showed that there was significant spatial, temporal, and spatiotemporal dependence in the evolution of the disease. For the first part of the epidemic, the cases were highly clustered in a few administrative units, in the proximity of the point of origin of the outbreak, possibly offering the opportunity to stop the spread of the disease. Later in the epidemic, high clusters were observed, but only in Liberia and Sierra Leone. Although not definitely factors of risk, in the setting in which the epidemic arose, our analysis suggests infrastructure, access to and use of health services, and connectivity possibly accelerated and magnified the spread of EVD. Also, the spatial, temporal, and spatiotemporal patterns of epidemic can be clearly shown - with evident application in the early stages of management of epidemics. In particular, we found that the spatial-temporal analytic tool SaTScan may be used effectively during the evolution of an epidemic to identify areas for targeted intervention. In the case of EVD epidemic in West Africa, better data and integration local knowledge and customs may have been more useful to recognize the proper response.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

Seroprevalence of Borrelia burgdorferi in Romania.

In order to assess the seroprevalence of Borrelia burgdorferi in Romania and to define associated risk factors, a cross-sectional, observational study was performed in 13 districts during 1999. Sera from healthy blood donors (1,598) and from forestry workers (1,048) were tested. A two-step testing strategy was used in which sera were tested for anti-B. burgdorferi antibodies by a commercially available passive hemagglutination assays (PHA). All PHA positive sera were then evaluated by Western blot IgG. Demographic data regarding age, sex, profession, work place/residence, duration of employment (forestry workers), animals in the environment, and tick bites history were collected using a questionnaire. Data obtained from serological study were matched with that obtained from the questionnaire. The seroprevalence of B. burgdorferi in blood donors was of 4.3% (range 1.4-8.7%) and 9.3% (range 2.8-31.7%) in forestry workers. Seroprevalence was higher in forestry workers with a tick bite history (10.7 vs. 4.3%, p < 0.05). The highest seroprevalence in blood donors (8.7%) was noted in Maramures, a northern district of the country, whereas in forestry workers the highest seroprevalence (31.7%) was observed in a western district (Arad), where a previous study in entomology has demonstrated the highest density of Ixodes ricinus ticks in Romania.

Relationship between whole-body protein turnover and serum creatinine in chronically uremic patients.

To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 +/- 0.4 (SE) mg x dl(-1); range 3.3-9.1). Patients' age and body mass index were 53 +/- 4 years (range 26-73) and 24.7 +/- 0.6 kg/m2 (range 20.3-28.7), respectively. Nutritional status (plasma albumin 3.6 +/- 0.4 g x dl[-1]) and acid-base equilibrium (arterial pH 7.38 +/- 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-(13)C]leucine was continuously infused and plasma [1-(13)C]alpha-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Rawas 2.03 +/- 0.13 micromol x kg(-1) x min(-1) (range 1.29-3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.

Mechanisms of malnutrition in uremia.

The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.

Lipid and apolipoprotein patterns during erythropoietin therapy: roles of erythropoietin, route of administration, and diet.

BACKGROUND: Long-term effects of rHuEpo on the blood lipid profile have not been well documented. The aim of this paper is to prospectively evaluate whether rHuEpo therapy affects lipid metabolism, and whether these effects are influenced by changes in dietary habits and by route of rHuEpo administration. METHODS: The study was performed in 33 maintenance haemodialysis patients (MHP) treated for one year with rHuEpo either intravenously (n = 15) or subcutaneously (n = 18), three times per week at the end of each dialysis session. The doses were 50 IU/kg intravenously or 35 IU/kg subcutaneously during the first 6 months and 20 IU/kg during the following months. The control group consisted of 17 MHP not treated with rHuEpo. Total cholesterol, LDL-cholesterol and HDL-cholesterol, triglycerides, apolipoproteins Al and B, haemoglobin, serum albumin, blood urea nitrogen, serum creatinine, Kt/V, protein catabolic rate, and plasma erythropoietin were assessed at months 0, 2, 4, 6, 9, 12 and 2 weeks after rHuEpo discontinuation. Changes in food intake were evaluated on the basis of weekly dietary diaries before, and 3 and 9 months after treatment. Patients were divided into two groups: group A consisted of 19 patients who showed an increase in their energy intake (10% or more of basal value), and group B was formed by 14 patients without or with slight changes in their food intake. After the 6th month, dialysis schedules were adapted to new protein catabolic rate values in patients who increased their food intake. RESULTS: During follow-up, there were no significant changes in any of the parameters in the control group. In group A, blood urea nitrogen, serum creatinine, protein catabolic rate, cholesterol, LDL cholesterol, triglycerides and apolipoprotein B increased significantly since the first months of rHuEpo treatment, and changes in cholesterol and apolipoprotein B correlated significantly with changes in protein catabolic rate. In group B, cholesterol, LDL cholesterol, and apolipoprotein B decreased significantly after the 6th month of treatment, without changes in blood urea nitrogen, serum creatinine and protein catabolic rate values. In both groups A and B, HDL cholesterol decreased significantly until the 6th month and returned to basal values in the following months and apolipoprotein Al decreased until the 4th month and rose to levels higher than basal values in the following months. First rHuEpo administration and rHuEpo suspension at end of follow-up did not show any acute effect on lipid profile, despite significant changes in plasma erythropoietin values. Changes in lipid profile were similar with intravenous and subcutaneous administration of rHuEpo. CONCLUSIONS: We infer that long-term rHuEpo treatment positively affects the lipid profile, but in some patients who show exaggerated increase in their food intake these effects may be balanced and overcome by increment in some atherogenic blood lipid fractions. The changes in lipid and apolipoprotein patterns during rHuEpo therapy are not influenced by route of rHuEpo administration.

Early and late effects of erythropoietin on glucose metabolism in maintenance hemodialysis patients.

The effects of recombinant human erythropoietin (rHuEPO) on the glucose metabolism were evaluated by intravenous glucose tolerance test in 20 maintenance hemodialysis patients. In 8 cases the glucose tolerance tests were performed before and after a single intravenous injection of 50 IU/kg of rHuEPO and in 12 cases before and after 3 months of rHuEPO therapy at doses of 50 IU/kg three times/week and 2 weeks after rHuEPO withdrawal. For each test glucose, immunoreactive insulin (IRI) and C peptide (C-p) plasma values were measured, and glucose constant decay, whole IRI (area IRI) and C-p area C-p) production, insulinogenic index, and insulin resistance index were calculated. After 3 months of rHuEPO therapy, the glucose constant decay increased significantly, area IRI, area C-p, and insulin resistance index decreased significantly, and the insulinogenic index did not change. No correlations were found between changes in hemoglobin values and changes in glucose metabolism parameters. Acute rHuEPO administration and rHuEPO withdrawal had no effect on glucose metabolism, despite significant changes in plasma erythropoietin levels. Long-term rHuEPO therapy improves glucose metabolism in maintenance hemodialysis patients significantly, mainly by reduction of insulin resistance. Neither anemia correction nor a direct effect of rHuEPO on some metabolic steps seem to be responsible of these effects.

Erythropoietin and cardiovascular risk.

We studied the changes in some cardiovascular risk (CVR) factors in 24 maintenance hemodialysis patients treated for 1 year with recombinant human erythropoietin (rHuEPO) either intravenously (12 cases) or subcutaneously (12 cases). In order to clarify whether changes in some parameters were due to direct action of rHuEPO or to changes in food intake, we divided the patients into two groups: group A was formed by 14 patients who showed an increase in their food intake during rHuEPO therapy and group B by 10 patients without or with slight changes in their food intake. rHuEPO induced an improvement in well-being in 20 of 24 patients and in physical working capacity in 14 of 24, an increase in mean blood pressure in all patients, and hypertension in 4 of 24 patients. The incidence of hypertension was slightly higher after intravenous (3/12) than after subcutaneous (1/12) treatment. The rate of dialysis treatment with symptomatic hypertension significantly decreased from 44.0 +/- 8.0 to 12.1 +/- 2.2% after intravenous and from 41.3 +/- 6.8 to 10.0 +/- 3.8% after subcutaneous treatment. Evaluation of glucose metabolism (intravenous glucose tolerance test) before and after 3 months of rHuEPO therapy showed an improvement in glucose utilization (insulin resistance reduction). Cholesterol (CH), low-density lipoprotein CH, triglycerides, and apolipoprotein B significantly increased in group A, but not in group B. Both in groups A and B, high-density lipoprotein CH significantly decreased during the first 6 months and returned to basal values during the following months, and the apolipoprotein A1 level significantly decreased during the first 4 months and increased to levels higher than basal values during the following months. Changes in CH and apolipoprotein B were also positively correlated with changes in the protein catabolic rate. We infer that rHuEPO has opposite effects on CVR, but subcutaneous administration, dietary control, and antihypertensive treatment may produce a net decrease in CVR of maintenance hemodialysis patients on rHuEPO therapy.

Glucose-induced insulin secretion in uremia: role of 1 alpha,25(HO)2-vitamin D3.

To evaluate the role and mechanism of action of calcitriol on glucose-induced insulin secretion in uremia, 17 patients with severe chronic renal failure were studied. Glucose metabolism was investigated by the intravenous glucose tolerance test (IVGTT) before and after treatment for 21 days with 0.5 microgram/day of calcitriol and 500 mg/day of calcium (C+Ca) (6 cases) or 0.5 microgram/day of calcitriol alone (C) (11 cases). After these evaluations the patients on C+Ca were shifted to C and 6 patients on C were shifted to C+Ca, and IVGTT was repeated 21 days after the shift. For each test plasma glucose (G), immunoreactive insulin (IRI) and C-peptide (C-p) were measured at -30, 0, 2, 5, 15, 30, 45, 60 min, and baseline plasma values of 1 alpha,25(HO)2-vitamin D3, C-terminal parathyroid hormone (PTH-C), intact parathyroid hormone (PTH-I), calcitonin, and serum values of total and ionized calcium were dosed. Also, glucose constant decay (K-G), insulin response (IRI area), C-p production (C-p area), insulinogenic index (IGI) and insulin resistance index (RI) were calculated. A historical group of 21 healthy volunteers formed the normal controls. 1 alpha,25(HO)2-vitamin D3 plasma levels in uremic patients before treatment were significantly lower than normal range. As compared to controls, uremic patients showed significantly lower K-G, IRI area and IGI values and significantly higher RI values. After treatment with C or C+Ca, the insulin response improved significantly at 2 and 5 min and G decrement was more marked at 30, 45 and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose-induced insulin secretion in uremia: relation with acid-base balance and effects of bicarbonate administration.

In order to evaluate effects of metabolic acidosis on glucose metabolism in uremia, we studied, by an intravenous glucose tolerance test (IVGTT), 46 patients with severe chronic renal failure divided into three groups according to their blood bicarbonate (BB) values: group A formed by 15 patients without or with light metabolic acidosis (BB > or = 20 mEq/1); group B formed by 18 patients with moderate metabolic acidosis (16 < or = BB < 20 mEq/1); group C formed by 13 patients with severe metabolic acidosis (BB < 16 mEq/1). In 8 patients of group B (subgroup B1) and in 8 of group C (subgroup C1), IVGTT was also repeated after adjustment of acid-base balance by intravenous or oral bicarbonate administration. Twenty-nine healthy volunteers formed the normal controls. For each test, glucose constant decay (K), immunoreactive insulin (IRI) area and C-peptide (C-p) area response, insulinogenic index (IGI) and insulin resistance index (RI) were calculated. Compared to controls, all uremic groups showed significantly lower values of K and IGI and significantly higher values of C-p area and RI. In group C, RI was significantly higher than in groups A and B. No differences were found in the other glucose metabolism parameters among the uremic groups. After bicarbonate administration, subgroup C1 showed a significant decrease in RI and a rise in K values, while subgroup B1 showed no changes in glucose metabolism parameters. From these data, we infer that abnormalities of acid-base balance do not affect insulin response but severe metabolic acidosis may play an additional role in the insulin resistance of uremic patients.

Immune response after vaccination with recombinant hepatitis surface antigen in maintenance hemodialysis patients and healthy controls.

We evaluated anti-HBs titers 2 months after vaccination with recombinant hepatitis surface antigen (rDNA-HBsAg) in 43 maintenance hemodialysis patients (MHP). Of these, 34 had not undergone hepatitis B virus vaccination previously (NV-MHP) and 9 had shown negative response to vaccination with plasma-derived HBsAg (HEVAC Pasteur; V-MHP). 120 healthy workers from the same hospital undergoing rDNA-HBsAg immunization were used as controls. All low responders (LR) (anti-HBs less than 100 mIU/ml) and nonresponders (NR; anti-HBs less than 10 mIU/ml) were given a booster dose 3 months after the last dose of vaccine. Seroconversion rates were lower in NV-MHP (52.9%) than in controls (98.4%). V-MHP showed higher seroconversion rates (88.9%) than NV-MHP. In each group, the number of responders (R; anti-HBs greater than or equal to 100 mIU/ml), LR and NR was as follows: controls 101, 17, 2; NV-MHP 6, 12, 16; V-MHP 8, 0, 1. After booster dose, 17/17 controls LR and no NV-MHP LR showed a rise in anti-HBs titers over 100 mIU/ml. Six months after the last dose of vaccine or the booster dose, anti-HBs titer fell under 10 mIU/ml in 4/12 MHP LR and under 100 mIU/ml in 6/14 MHP R. To achieve high seroconversion rates and to avoid the decline of anti-HBs to nonprotective titers in MHP, a booster injection should be made at different dates after the first vaccination.

Prospective and retrospective assessment of clinical and laboratory parameters in maintenance hemodialysis patients with and without HCV antibodies.

In order to clear some aspects of HCV infection, we evaluated quarterly HCV markers by a RIBA 1 test (antigens c100-3 and 5.1.1) and monthly transaminases (ALT and AST) for 14 months in 89 HBsAg-free maintenance hemodialysis patients (MHP), and we retrospectively examined clinical records until the start of hemodialysis treatment. At the start of the study, 16 patients showed HCV antibodies (HCV+) and 73 were antibody-free (HCV-). 39 subjects of the staff were also examined. No HCV+ patient showed seroconversion, 10 showed irregular or persistent elevation of AST and ALT. In the retrospective evaluation 14 patients suffered from acute hepatitis (AH). Only 3 cases showed temporal relation with blood transfusions. In 1 case a 36-month temporary normalization of transaminases was noticed. 3 HCV-patients showed seroconversion (1 during AH), 13 showed severe or moderate elevations of transaminases. In the retrospective evaluation, 6 patients suffered from AH. All subjects of the staff were HCV- and showed no seroconversion or changes of transaminases. At the end of the study, we performed a RIBA 2 test containing the HCV antigens c100-3, 5.1.1, c22-3 and c33c. The 6 patients who suffered from AH showed at least 1 positivity for new proteins. Most of AH in MHP are likely due to HCV infection; besides transfusions, cross-infection during the dialytic procedure may be responsible for many cases of HCV infection; long-term normalization of transaminases may not secure against infectivity.

Peripheral adrenoceptors in hypotension of hemodialyzed uremic patients.

Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet alpha 2-adrenoceptors and the activity of lymphomonocyte beta 2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of alpha 2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of beta 2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of alpha 2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 +/- 195 vs. 344 +/- 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 +/- 30 vs. 94 +/- 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 +/- 2.4 vs. 15.6 +/- 5.4 pmol/10(6) cells; p < 0.002). The increased number of alpha 2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with beta 2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor coupling mechanisms.

Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments.

The study was carried out in order to evaluate in maintenance hemodialysis (MH) patients: (1) the reliability of serum ferritin (SF) measurement in iron deficiency diagnosis and therapy; (2) the possibility to improve iron stores assessment through laboratory indexes routinely used in clinical practice; (3) the most effective iron deficiency treatment. After a preliminary assessment of SF reference values in 250 healthy volunteers, we studied 72 MH patients divided into three groups according to their SF baseline values: high (group A), normal (group B), low (group C) (normal range 19-191 ng/ml). Each group was further divided into three subgroups receiving three different iron treatments for 6 months: (1) oral administration of 67.5 mg/day of Fe3+ as Fe-ferritin (subgroups A1, B1, C1); (2) oral administration of 60 mg/day of Fe3+ as Fe-chondroitin sulfate (subgroups A2, B2, C2); (3) i.v. administration at the end of each dialytic session of 31 mg of Fe3+ as Fe-gluconate-Na (subgroups A3, B3, C3). The response to the iron therapy was considered positive when the hemoglobin (Hb) and the hematocrit (Ht) increased to greater than or equal to 15% of the baseline values. The rate of positive responses in each subgroup was as follows: A1 0/5, A2 0/5, A3 0/7, B1 2/10, B2 1/6, B3 5/11, C1 1/7, C2 3/7, C3 10/16. We concluded that SF values above 191 ng/ml allow to exclude iron deficiency whereas SF values less than or equal to the normal range are inadequate. In an attempt to improve diagnostic sensitivity we divided patients of subgroup B3 and C3 into responders (R) and nonresponders (NR).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose-induced insulin secretion in uremia: effects of aminophylline infusion and glucose loads.

To explain mechanisms responsible for derangement of insulin release in uremia, we investigated glucose metabolism through three different tests in 14 patients with end-stage chronic renal failure. These tests were: intravenous glucose tolerance test with 0.33 g/kg of glucose solution (IVGTT); IVGTT with 0.5 g/kg of glucose solution (IVGTT2); IVGTT during aminophylline infusion (IVGTT + A). Twelve of the patients had IVGTT repeated after two to four months of thrice-weekly regular hemodialysis (IVGTT3). In each test we measured plasma glucose (G), immunoreactive insulin (IRI) and C-peptide. We also calculated glucose constant decay (K), insulin production (IRI area), insulinogenic index (IGI), and insulin resistance index (RI). Twenty-nine healthy volunteers formed the normal controls for IVGTT. As compared to controls, during IVGTT uremic patients showed significantly lower values in K, IRI area and IGI, and showed a significant RI value increase. During IVGTT2, IRI are values were higher than during IVGTT but IGI and K values were unchanged. During IVGTT + A both IRI area and IGI values were higher than during IVGTT. After hemodialysis treatment (IVGTT3) K, IRI areas and IGI increased significantly as compared to the predialysis period. K increase after hemodialysis correlated directly to IGI increase and inversely to RI changes. IGI increase during IVGTT3 was directly correlated to IGI rise during IVGTT + A. From these data we infer that defective insulin release in uremia is due to a decrease of beta-cell glucose sensitivity rather than to their functional exhaustion. An impaired adenyl cyclase-cAMP system may have an important role in the pathogenesis of this abnormality.