Modelling the dynamics of dengue real epidemics.

In this work, we use a mathematical model for dengue transmission with the aim of analysing and comparing two dengue epidemics that occurred in Salvador, Brazil, in 1995-1996 and 2002. Using real data, we obtain the force of infection, Λ, and the basic reproductive number, R(0), for both epidemics. We also obtain the time evolution of the effective reproduction number, R(t), which results in a very suitable measure to compare the patterns of both epidemics. Based on the analysis of the behaviour of R(0) and R(t) in relation to the adult mosquito control parameter of the model, we show that the control applied only to the adult stage of the mosquito population is not sufficient to stop dengue transmission, emphasizing the importance of applying the control to the aquatic phase of the mosquito.

Periodic forcing in a three-level cellular automata model for a vector-transmitted disease.

A periodically forced two-dimensional cellular automata model is used to reproduce and analyze the complex spatiotemporal patterns observed in the transmission of vector infectious diseases. The system, which comprises three population levels, is introduced to describe complex features of the dynamics of the vector-transmitted dengue epidemics, known to be very sensitive to seasonal variables. The three coupled levels represent the human, the adult, and immature vector populations. The dynamics includes external seasonality forcing, human and mosquito mobility, and vector control effects. The model parameters, even if bounded to well-defined intervals obtained from reported data, can be selected to reproduce specific epidemic outbursts. In the current study, explicit results are obtained by comparison with actual data retrieved from the time series of dengue epidemics in two cities in Brazil. The results show fluctuations that are not captured by mean-field models. It also reveals the qualitative behavior of the spatiotemporal patterns of the epidemics. In the extreme situation of the absence of external periodic drive, the model predicts a completely distinct long-time evolution. The model is robust in the sense that it is able to reproduce the time series of dengue epidemics of different cities, provided that the forcing term takes into account the local rainfall modulation. Finally, an analysis is provided of the effect of the dependence between epidemics threshold and vector control actions, both in the presence and absence of human mobility factor.

Pharmacological nutrition in inflammatory bowel diseases.

Inflammatory Bowel Diseases--ulcerative colitis and Crohn's disease--are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.

Epidemiologia do dengue em Salvador-Bahia, 1995-1999 / Epidemiology of dengue in Salvador-Bahia, 1995-1999

Since 1981, Brazil has registered dengue epidemic and simultaneous circulation of the DEN-1 and DEN-2 serotypes in over 2,700 municipalities. In Salvador- Bahia, located in the Northeastern region of the Country, two epidemic outbreaks occurred in the years of 1995 and 1996, with further endemic spread of the disease. This study analyses the incidence of the virosis within this municipal area, from 1995 to 1999, considering, among other variables, its distribution in the Sanitary Districts and density of Aedes aegypti. Registers of notified cases and the city's Vectorial Control Program were used as data source. The incidence rate of notified cases of dengue in 1995 and 1996, which were 691.4 and 393.5 per 100,000 inhabitants, respectively, decreased to 65 per 100,000 inhabitants in 1998. In the poorer Sanitary Districts, this index reached figures of over 800 per 100,000 inhabitants. The Premise Index for Aedes aegypti reached 54.1% in one of the Districts. Bearing in mind the relevance of the re-emergence of dengue in the world, the authors discuss the possible factors which condition the virus introduction, its epidemiological presentation over the course of four years, and the effectiveness of the vectorial combat (eradication) program.

Desde 1981, o Brasil tem registrado epidemias de dengue de grande magnitude e atualmente circulam simultaneamente dois sorotipos DEN-1 e DEN¾2, em mais de 2.700 municípios. Em Salvador - Bahia, situada na Região Nordeste do país, ocorreram duas epidemias nos anos de 1995 e 1996, e posterior endemização da doença. Este estudo analisa a incidência desta virose nesse município, no período de 1995 a 1999, considerando entre outras variáveis, sua distribuição nos Distritos Sanitários e a situação de densidade do Aedes aegypti. Utiliza como fonte de dados registros oficiais de notificação e do programa de combate vetorial da cidade. A taxa de incidência de dengue foi de 691,4 e 393,5 por 100.000 habitantes, respectivamente, em 1995 e 1996, reduziu-se para 65 por 100.000 em 1998. Nos Distritos Sanitários mais carentes, este indicador alcançou valores superiores a 800 por 100.000 habitantes. O Índice de Infestação Predial pelo Aedes chegou a atingir 54,1% em um dos seus bairros. Considerando a importância da reemergência do dengue no mundo os autores discutem os possíveis fatores que condicionaram a introdução do vírus, as suas apresentações epidemiológicas no curso de 4 anos, e a efetividade do programa de combate vetorial.

Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs.

A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits or telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14,000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns.

A recombinant peptide antigen line immunoassay optimized for the confirmation of Chagas' disease.

BACKGROUND: The transfusion of contaminated blood has become the major route of transmission for Chagas' disease in Brazil. Current screening tests are insensitive and yield conflicting results, while confirmatory assays do not exist. A line immunoassay (INNO-LIA Chagas Ab [INNO-LIA]) combining relevant, immunodominant recombinant and synthetic antigens on a single nylon membrane strip was evaluated for the serologic confirmation of Chagas' disease. STUDY DESIGN AND METHODS: Sera from 1062 patients and healthy residents of four Brazilian regions endemic for Chagas' disease were used for test optimization. The established confirmation algorithm was evaluated with an independent set of positive (n = 75) and negative (n = 148) samples. RESULTS: In the optimization phase, without an established comparative gold standard, the results with the INNO-LIA were compared with those obtained in four other screening assays. In the validation phase, the INNO-LIA showed a sensitivity of 100 percent (95% CI, 95.21-100) and a specificity of 99.32 percent (95% CI, 96.29-99.98) for well-characterized sera. Moreover, its specificity reached 100 percent with a set of 40 sera obtained from patients with documented leishmaniasis. The interpretation criteria defined in this study indicated that the INNO-LIA accurately detected the presence of antibodies to various specific antigens of Trypanosoma cruzi. CONCLUSION: The INNO-LIA Chagas Ab assay may become the first commercial assay to reliably confirm the presence of antibodies to T. cruzi.

Pouchitis: extracolonic manifestation of ulcerative colitis?

Pouchitis is the most frequent complication of ileal pouch-anal anastomosis for treatment of ulcerative colitis. There are several possible explanations. Among them, we focus on the one that considers pouchitis as an extracolonic manifestation of ulcerative colitis. The aim of this study was to investigate the association between pouchitis and extra-intestinal manifestations (EIM), which are frequent in these patients. Sixty patients underwent restorative proctocolectomy with an ileal J pouch (IPAA) from September 1984 to December 1998. Pouchitis was defined by clinical, endoscopic, and histologic criteria. The following extra-intestinal manifestations were studied: articular, cutaneous, hepatobiliary, ocular, genitourinary, and growth failure. Thirteen patients, of which 10 were female (76.9%), developed one or more episodes of pouchitis. Twelve patients of this group (92.3%) presented some kind of extra-intestinal manifestation, 4 pre-operatively (exclusively), 2 post-operatively (exclusively), and 6 both pre- and post-operatively (1.7 per patient). Twenty patients (42.7%) of the 47 without pouchitis did not present extra-intestinal manifestations; 10/35 (28. 5%) of females had pouchitis, compared to 3/35 (12.0%) of men. Pouchitis was more frequent among females, though not statistically significant. EIM increases the risk of pouchitis. Pouchitis is related to EIM in 92.3 % of cases, corroborating the hypothesis that it could be an extracolonic manifestation of ulcerative colitis.

Mechanism of action of interferon-tau in the uterus during early pregnancy.

Early pregnancy is maintained in ruminants through the actions of conceptus-derived interferon (IFN)-tau on the endometrium. IFN-tau alters uterine release of PGF2 alpha' which results in rescue of the corpus luteum and continued release of progesterone. The mechanism of action of IFN-tau includes inhibition of oestradiol receptors, consequent reduction in oxytocin receptors, activation of a cyclooxygenase inhibitor, and a shift in the PGs to favour PGE2 over PGF2 alpha' IFN-tau also induces several endometrial proteins that may be critical for survival of the developing embryo. One endometrial protein induced by pregnancy and IFN-tau has been identified as bovine granulocyte chemotactic protein-2 (bGCP-2). This chemotactic cytokine (chemokine) has been used as a marker to delineate IFN-tau from IFN-alpha responses in the endometrium. A second protein, called ubiquitin cross-reactive protein (UCRP), resembles a tandem ubiquitin repeat. UCRP becomes conjugated to cytosolic endometrial proteins in response to IFN-tau and pregnancy. Proteins conjugated to UCRP are either modulated or targeted for processing through the proteasome. The action of IFN-tau is mediated by induction of signal transducer and activator of transcription 1 (STAT-1), STAT-2 and interferon regulatory factor 1 (IRF-1) transcription factors. Induction of these transcription factors, the alpha chemokines and UCRP is the prelude to maternal recognition of pregnancy in ruminants.

[Colonic Crohn's disease: results of treatment]. / Doença de Crohn exclusiva no intestino grosso: resultados do tratamento.

Sixty patients with Crohn's colitis were separated into 2 groups: A) without perianal lesions, 12 patients; B) with perianal lesions, 48 patients. The mean age at the beginning of symptomatology was 41.4 years in group A and 31.7 in B. The number of patients that underwent surgical treatment were similar in both groups. Fifty eight operations were performed in 29 patients, mean 0.33 operations/patient in group A and 2.16 in B. Ileal pouch anal anastomosis were performed in 5 patients, with loss of reservoir in one. There was no difference in need of hospitalization between the 2 groups. At mean follow-up of 8.9 years, 37 patients presented at least one extra-intestinal manifestation, 21 a perianal lesion, 39 were taking drugs and 31 were symptomatic. In the group of 31 patients that received only medical treatment, 24 (77.4%) are still on drugs and only 9 are assymptomatic. In the group of 29 patients that were operated on, 12 (41.4%) are taking drugs and 19 (65.5%) are assymptomatic. The difference concerning results of treatment between patients on medical treatment and operated were statistically significant. A permanent ileostomy was performed in 19(65.5%) patients. Two patients died during clinical treatment and one of postoperative complications.

Complex induction of bovine uterine proteins by interferon-tau.

Interferon-tau (IFN-tau) is released by the conceptus and induces two uterine proteins during early pregnancy: ubiquitin cross-reactive protein (UCRP) and granulocyte chemotactic protein-2 (GCP-2). The present experiments were designed to determine whether detection (Western blot) of cytosolic UCRP and release of GCP-2 could be used to examine IFN-tau signal transduction in cultured endometrial explants and primary epithelial cells. Recombinant (r) type 1 IFNs (rboIFN-tau and rboIFN-alpha; 5, 25, 100 nM) induced UCRP, but only rboIFN-tau induced GCP-2 in explant culture. Recombinant boIFN-tau and conceptus secretory proteins containing native IFN-tau induced UCRP and GCP-2 in cultured primary epithelial cells. All concentrations of rboIFN-alpha (25, 50, 100 nM) induced UCRP, but only the highest concentration induced GCP-2 in cultured primary epithelial cells. Interestingly, phorbol ester (100, 500, 1000 ng/ml) induced GCP-2, but it had no effect on UCRP. Because type 1 IFNs induce UCRP, IFN-tau probably interacts with the janus kinase (Jak)-associated IFN-alpha receptor to phosphorylate signal transducers and activators of transcription (STAT) and/or interferon regulatory factor-1 (IRF-1). However, IFN-tau-specific induction of GCP-2 may involve a variant type 1 receptor subunit or activators of transcription that are associated with protein kinase C and the Jak/STAT/IRF-1 pathway.

Bovine granulocyte chemotactic protein-2 is secreted by the endometrium in response to interferon-tau (IFN-tau).

Interferon-tau (IFN-tau) is secreted by the bovine conceptus and may regulate synthesis of uterine endometrial cytokines to provide an environment that is conductive to embryo development and implantation. Interferon-tau stimulates secretion of an 8-kDa uterine protein (P8) in the cow. P8 was purified, digested to yield internal peptides, and partially sequenced to determine identity. Two internal peptides had 100% (13-mer) and 92% (12-mer) amino acid sequence identity with bovine granulocyte chemotactic protein-2 (bGCP-2). Bovine GCP-2 is an alpha-chemokine that acts primarily as a potent chemoattractant for granulocyte cells of the immune system. A peptide was synthesized based on a region of bGCP-2 that overlapped with a P8 peptide amino acid sequence, coupled to keyhole limpet hemocyanin, and used to generate high titer polyclonal antiserum in sheep. Western blots revealed that bGCP-2 was not released by endometrium from day 14 nonpregnant cows, but was released in response to 25 nM IFN-tau (p<0.05). Uterine GCP-2 exhibited high affinity to heparin agarose, a characteristic shared by all alpha chemokines. This is the first report describing presence of GCP-2 in the uterine endometrium and regulation by IFN-tau. The regulation of bGCP-2 by IFN-tau may have important implications for cytokine networking in the uterus during pregnancy. Also, the regulation of inflammation and angiogenesis by bGCP-2 working together with other cytokines may be integral to establishing early pregnancy and implantation in the cow.

Effects of colectomy on gallbladder motility in patients with ulcerative colitis.

In order to gain insight into the possible mechanisms involved in gallstone formation in colectomized ulcerative colitis patients, we studied gallbladder motility by means of ultrasonography in three groups of subjects: controls (N = 40) and ulcerative colitis patients without (N = 30) and with (N = 20) colectomy. Impaired gallbladder emptying after a liquid fatty meal stimulus was observed in ulcerative colitis patients with colectomy compared with those obtained in ulcerative colitis patients without colectomy and controls (P = 0.001). The maximum percentage of gallbladder emptying also, was significantly lower (59.8%) than those seen in ulcerative colitis patients without colectomy (74.5%) and controls (77.8%) (P = 0.001). Diminished gallbladder emptying with ensuing stasis might be a contributory factor to the increased prevalence of gallstones in colectomized patients.

[Prevalence of anal incontinence in the elderly population: an epidemiological study of the elderly population served at the geriatric ambulatory service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo]. / Prevalência da incontinência anal no idoso: estudo epidemiológico com base na população atendida no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, em regime ambulatorial.

The aim of the present work was to assess the prevalence of anal incontinence in the elderly population attended in the "Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo". The method employed was of individual interviews with patient attended in the Geriatric Ambulatory. As part of the assessment patients were classified as to sex, age, color, social-economical class and education, and compared to available data on the elderly population of the State and the City of São Paulo. Besides the question on signs and symptoms related to anal incontinence, associated factors such as bowel habit, sensation of incomplete evacuation, urgency to evacuate and soiling were also analysed, as well as, factors possibly related to anal incontinence such as urinary incontinence, use of medication as laxatives, associated diseases, such as neurological affections and diabetes mellitus, number of child births, and assistance received, previous anorectal or perineals operations, and locomotions limiting factor. The statistical method of test of proportion was used to analyse the proportions of the populations interviewed, as to sex and literacy compared to the elderly population of the State and City of São Paulo. To analyse the social-economical class of the population interviewed compared to the elderly population economically and non economically active, of the State of São Paulo, the test of qui-square adjusted was used. The test of qui-square was used to verify if the population of incontinent and continent, by sex; incontinent and continent in relation to bowel habit, by sex; incontinence sufferer of continuous and descontinuous anal incontinence, by sex; incontinent sufferer of anal incontinence to gas, liquid or solid, and the association of these manifestations, by sex; patients who complained of soiling, by sex; incontinent and continent, previously submitted to anorectal or perineal operations; and continent and incontinent with diabetes mellitus, are equal. To verify the proportions of women who had vaginal delivery in the continent and incontinent group, the test of Mann-Whitney was used. One hundred fourty six patients were interviewed, 43 men of an average 75 years old (62 to 91) and 103 women of an average 72 years old (60 to 88); as to colours, 69.9% were white, 18.5% were mullato, 9.6% were black and 2% were yellow. The comparative analysis with populational data indicated that the population interviewed was representative of the elderly population of the State and the City of São Paulo, as to age, color, social-economical class and education. The prevalence of anal incontinence was of 10.9% with no difference between the sexes, intestinal obstipation referred by 15.4% of the men and 28.1% of the women, sensation of incomplete evacuation referred by 21.2% of the patients, and the association of both referred by 13.7% were the most frequently observed functional gastrointestinal alterations. Soiling was referred by 10.3% of the patients with no difference related to sex. The use of medication or laxatives, the presence of diabetes mellitus, neurological affections, previews anorectal or perineal operations, or locomotion limiting factors, have no relation to anal incontinence. The prevalence of urinary incontinence was of 30.1%, and double continence of 6.3% with no statistical difference between sexes. There was statistical evidence of association between childbearing and anal incontinence.

[Prevalence of fecal incontinence in diabetic patients: epidemiological study of patients assisted as outpatients at the Clinical Hospital of the Medical School at the University of São Paulo]. / Prevalência da incontinência anal no diabético: estudo epidemiológico com base na população atendida em regime ambulatorial no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.

The object of this research was to establish the prevalence of fecal incontinence in those diabetics attended as outpatients at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Individual verbal interviewing was the an adopted method. The classification of diabetes mellitus of World Health Organization was employed (1985). Data was aggregated relative sex, age, color, type of diabetes mellitus, fecal incontinence, duration of diabetes mellitus, peripheral neuropathy, intestinal habits (normal, constipation and diarrhea), urgency to evacuate, sensation of incomplete evacuation, urinary incontinence, vaginal deliveries and its characteristics. The study involved 258 diabetics, 167 of female sex having an average age of 56.2 years (17 to 78 years of age) and 91 of the male sex having average age of 55.8 years (10 to 74 years of age). With relation to color, 57% were white, 28.7% mullato, 11.2% black and 3.1% yellow. Fecal incontinence was prevalent in 18.6% of the cases studied. It occurred also in types I and II diabetics with predominance in the male sex. It also occurred in diabetics having an average history of 10.8 years to onset of illness. Peripheral neuropathy was observed in 8.5% of the diabetics investigated however no association was observed between the peripheral neuropathy and fecal incontinence. Constipation occurred in 29.5% of the patients and diarrhea in 21.3%. Incomplete evacuation was apparent in 15.1% of diabetics and urgency to evacuate in 12.8%. A relationship was identified between fecal incontinence with diarrhea and incomplete evacuation in the group investigated. Total vaginal deliveries was 458 with 70 episiotomies and 25 by forceps. There was no statistical evidence of association between the average number of vaginal deliveries, episiotomies and forceps in diabetics demonstrating or not demonstrating fecal incontinence. Urinary incontinence was more prevalent that fecal incontinence. No relationship was determined between urinary and fecal incontinence for the purpose of the present study.

[Perianal manifestations in Crohn's disease]. / Manifestações perianais na doença de Crohn.

UNLABELLED: A total of 114 of 195 patients with Crohn's disease had perianal involvement. The average age at the beginning of symptomatology was 30.3 years. The interval between symptoms and diagnosis was 3.1 years. PAC was associated with colonic disease and in these patients, was multiple. PAC preceded intestinal disease in 11 percent, was coincident in 66 percent and appeared later in 23 percent. Sixty one patients (53.5%) were operated on 104 times (1.7 operations per patient). None of these patients developed faecal incontinence. Two patients were treated with hyperbaric oxygenation. The association of perianal disease and extra-intestinal manifestation occurred in 76 patients. There was no association in 38 patients. Forty patients had extra-intestinal manifestation without perianal disease. Twenty two patients had panproctocolectomy because of perianal disease. Twenty one had a stoma, with or without intestinal resection. The stoma improved perianal symptoms, but all remain defunctioned. After mean follow-up of 8.8 years, 45 patients present some kind of perianal complication. CONCLUSION: the surgical treatment of perianal disease well indicated and performed don't result in incontinence; PAC combined with colonic or rectal disease is associated with higher need of performing a proctocolectomy or a defunctioning stoma. Only 22.8 percent presented resolution of perianal disease maintaining anal sphincter function.

Ubiquitin cross-reactive protein is released by the bovine uterus in response to interferon during early pregnancy.

A 16-kDa protein has been identified that is secreted by the bovine endometrium in response to conceptus-derived interferon (IFN)-tau during early pregnancy. Because this uterine protein was similar in size to a human ubiquitin cross-reactive protein (hUCRP) that also was regulated by IFN, we suspected that they might be related. To test this hypothesis, uterine flushings, medium from cultured endometrium, and endometrial tissues were examined for the presence of ubiquitin-immunoreactive proteins. Immunoreacting proteins were detected through use of one-dimensional (1D)-PAGE and Western blotting with ubiquitin and hUCRP antiserum (1:500). A 16-kDa protein that cross-reacted with ubiquitin and hUCRP antisera was released by the endometrium and was present in uterine flushings from all Day 18 pregnant females examined (n = 12). The immunoreacting 16-kDa protein was absent in all nonpregnant females examined (n = 23). Regulation of this uterine protein by recombinant type I IFNs (rbIFN-tau, rbIFN-alpha, and roIFN-tau), using 0, 0.5, 5, and 25 nm of each IFN, was evaluated in nonpregnant (Day 12) heifers (n = 5) using 1D-PAGE and Western blotting. Release of the 16-kDa protein into medium was negligible in controls (0 nm IFN). For each IFN, a dose-dependent increase (p < 0.05) in release of the immunoreacting 16-kDa protein was noted. We conclude that the 16-kDa protein that is produced by the endometrium in response to IFN-tau during early pregnancy also shares epitopes with hUCRP and ubiquitin. The 16-kDa protein has been named bovine UCRP.