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APPLICATION OF COPPER BACTERICIDAL PROPERTIES IN MEDICAL PRACTICE Copper is essential for cell metabolism in animals and plants and thus for life. Along centuries, copper has been identified as a metal containing antimicrobial properties. In recent years, laboratory assays and clinical studies have revealed that surfaces of metallic copper or its alloys, containing at least 70% copper, eliminate in a few hours several pathogenic organisms including bacterial strains associated with nosocomial infections, influenza virus, HIV, and fungi such as Candida albicans . In March 2008, the American Environmental Protection Agency (EPA), supported by scientific evidence gathered to date, registered copper as the first and only metal with antimicrobial properties. We herein review certain mechanisms proposed for the antibacterial, antiviral and antifungal activity of copper. We also discuss in vitro and clinical efficacy studies developed world wide and in Chile, focusing on bactericidal activity of copper surface areas in comparison to materials typically used in hospital environments such as stainless steel and polymers. Scientific evidence gathered to date, consistently shows that the use of copper surface areas in high contact critical points in hospitals, significantly reduces environmental bacterial load. This is associated with a decreased risk of pathogen transmission to patients and represents therefore an interesting complement to infection control programs. Normal 0 21 false false false ES X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age.The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingestedor =70 ml were considered fully vaccinated.Only 37% of subjects overall (25% of 3- to 5-month-olds) ingestedor =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose.Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.

We compared the incidence of nasopharyngeal colonization by Streptococcus pneumoniae , the serotypes causing mucosal and invasive diseases, and the antibiotic resistance of these strains in patients admitted to three large hospitals and children attending day care centers in two Chilean cities (Santiago and Temuco). The populations in both cities were similar in ethnic background, socioeconomic status, family size, and access to medical care. Significant differences in nasopharyngeal colonization rates, in serotypes causing infections, and in antibiotic resistance were found between the two cities. In children 0 to 2 years of age, 42% were colonized with S. pneumoniae in Santiago compared to 14% in Temuco. A total of 41 serotypes were identified in both Chilean cities studied. Six serotypes were found only in Santiago; 14 serotypes were found only in Temuco. Antibiotic-resistant serotypes 6A, 6B, 14, 19F, and 23F were detected only in Santiago. We show that important differences in the incidence of nasopharyngeal carriage, infection, and S. pneumoniae serotypes can exist in similar populations in different areas of the same country. Our findings are relevant for prevention strategies, antibiotic usage, and vaccine design.

We previously demonstrated the immunogenicity and tolerability of the serogroup B meningococcal vaccine, 4CMenB (Bexsero®), in 11−17 y-olds randomized to receive 1, 2, or 3 doses at 1, 2, or 6 mo intervals. Participants in this extension study provided an additional blood sample 18−24 mo after last vaccine dose, to assess persistence of serum bactericidal activity with human complement (hSBA), and to compare with age-matched 4CMenB-naive controls. In the original study, one month after one 4CMenB dose, 93% of subjects had seroprotective hSBA titers (≥4) against indicator serogroup B strains for individual vaccine antigens (fHbp, NadA and NZOMV), increasing to ~100% after two or three doses. After 18−24 mo, 62−73% of subjects given one dose had titers ≥4 against the three antigens, significantly lower rates than after two (77−94%) or three (86−97%) doses. Only proportions with titers ≥ 4 against NZOMV were significantly different between the two (77%) and three (90%, p < 0.0001) dose groups. These results confirm that two doses of 4CMenB, administered 1 to 6 mo apart, provide good levels of bactericidal activity against serogroup B meningococci, which were sustained at least 18−24 mo in over 64% of adolescents for all three tested vaccine-related antigens.

Background We evaluated a dipstick test for rapid detection of Shigella sonnei on bacterial colonies, directly on stools and from rectal swabs because in actual field situations, most pathologic specimens for diagnosis correspond to stool samples or rectal swabs. Methodology/Principal Findings The test is based on the detection of S. sonnei lipopolysaccharide (LPS) O-side chains using phase I-specific monoclonal antibodies coupled to gold particles, and displayed on a one-step immunochromatographic dipstick. A concentration as low as 5 ng/ml of LPS was detected in distilled water and in reconstituted stools in 6 minutes. This is the optimal time for lecture to avoid errors of interpretation. In distilled water and in reconstituted stools, an unequivocal positive reaction was obtained with 4 x 106 CFU/ml of S. sonnei. The specificity was 100% when tested with a battery of Shigella and different unrelated strains. When tested on 342 rectal swabs in Chile, specificity (281/295) was 95.3% (95% CI: 92.9% - 97.7%) and sensitivity (47/47) was 100%. Stool cultures and the immunochromatographic test showed concordant results in 95.5 % of cases (328/342) in comparative studies. Positive and negative predictive values were 77% (95% CI: 65% - 86.5%) and 100% respectively. When tested on 219 stools in Chile, Vietnam, India and France, specificity (190/198) was 96% (95% CI 92%–98%) and sensitivity (21/21) was 100%. Stool cultures and the immunochromatographic test showed concordant results in 96.3 % of cases (211/219) in comparative studies. Positive and negative predictive values were 72.4% (95% CI 56.1%–88.6%) and 100 %, respectively. Conclusion This one-step dipstick test performed well for diagnosis of S. sonnei both on stools and on rectal swabs. These data confirm a preliminary study done in Chile.

Objective: 1) Evaluate the antimicrobial properties of copper in hearing aid molds against the most prevalent pathogens of otitis externa in an in vitro system. 2) Determine the most suitable mold material to allow adequate diffusion of copper ions to perform its antimicrobial action.Method: Experimental study conducted from January to December 2010, consisting of an in vitro system with hearing-aid molds made from different materials with and without copper in them, which were inoculated with external otitis pathogens at different concentrations (S aureus, P aeruginosa, C albicans, and A niger), then determine percentage of bacterial adhesion to materials.Results: There was a significant reduction in the percentage of microbial adherence to different mold materials with copper in them, in relation to those without copper, at different levels of microbial concentration for S aureus, P aeruginosa, C albicans, and A niger, while the percentages of adherence reduction fluctuated between 27% and 100% in those...

Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents.We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713.Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified.On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys.Novartis Vaccines and Diagnostics.

In Latin America, acute gastroenteritis remains to be an important cause of morbidity in adults and a major cause of morbidity and mortality in children. A child under 5 years of age belonging to a low income segment of the Latin American population will develop 5 to 10 bouts of diarrhea every year. The bacterial and viral enteropathogens associated with acute diarrhea are reviewed in this article. Updated information on epidemiologic, clinical, and pathogenic aspects for the relevant enteropathogens is discussed with special emphasis on regional data when available. The current diarrheogenic E. coli classification is particularly discussed. A diagnostic approach to acute gastroenteritis for both the clinical and research laboratories in Latin America as well as guidelines for treatment are proposed.

The incidence of diarrhea due to six categories of diarrheogenic Escherichia coli was determined in two pediatric cohorts in a low socioeconomic level community in Santiago, Chile, with access to chlorinated water. An age cross-sectional cohort of 340 children aged birth to 47 months was assembled. A newborn cohort was assembled by enrolling 10-12 newborns monthly for 12 months. Episodes of diarrhea were detected by twice weekly household visits. E. coli from stool cultures of cases and matched controls were hybridized with DNA probes specific for enterotoxigenic, enteroinvasive, enteropathogenic, enterohemorrhagic, enteroaggregative, and diffuse adherence E. coli. Overall, the incidence of diarrhea was low (2.1 episodes/infant/year). Nevertheless, a putative E. coli enteropathogen was found in a large proportion of diarrheal episodes, particularly during the summer. In both cohorts, enterotoxigenic E. coli were important pathogens. Enteropathogenic E. coli were incriminated during the first year of life in the newborn cohort, where they were found significantly more often in cases (p = 0.021) than in controls; beyond this age, isolation rates were similar. In contrast, the relative risk of isolation of diffuse adherence E. coli increased with age in the age cross-sectional cohort, where, overall, the difference in rate of isolation between cases and controls was significant (p = 0.0024). Enteroinvasive and enterohemorrhagic E. coli were isolated infrequently. Enteroaggregative E. coli were encountered equally in cases and controls. Facile transmission of E. coli enteropathogens is occurring in this community despite the availability of potable water.Researchers conducted an age cross sectional cohort analysis of 340 0-47 month old children and newborn cohort analysis of 144 newborns to determine the diarrheogenic Escherichia coli incidence in Santa Julia, a low socioeconomic community in Santiago, Chile. Children in the age cross sectional cohort had age, sex, and sector matched controls. The newborns had sex matched controls. A public health nurse or nurse auxiliary visited the household of each subject 2 times a week to detect diarrhea episodes. Between December 1986 and February 1990, the age cross sectional cohort had 1178 episodes of diarrhea and the newborn cohort had 674 episodes. The overall diarrhea incidence was only 2.1 episodes/child/year. An E. coli enteropathogen was isolated in many of these episodes, especially during the summer (e.g. enterotoxigenic E. coli [ETEC], 2.2 cases/month in summer vs. 0.4 cases/month in winter; p = .00001). Diffuse adherence E. coli (DAEC) and enteropathogenic E. coli (EPEC) infections also peaked in the summer. ETEC contributed greatly to diarrheal episodes in both cohorts. Among newborns, EPEC was isolated significantly more often in cases than controls during the 1st 12 months of life (6.7% vs. 2.5%; p = .021). After 1 year, however, E. coli isolation rates were essentially the same. On the other hand, in the age cross sectional cohort, the relative risk of isolation of DAEC rose with age (e.g., 1.1 for 0.11 months, 1.4 for 36-47 months, and 2.1 for = or 48 months). In the same cohort, DAEC infections were much more common in cases than controls (16.6% vs. 11.9%; p = .0024). Enteroinvasive and enterohemorrhagic E. coli were the most rarely isolated E. coli types. No difference in the isolation rate of enteroaggregative E. coli existed between cases and controls. Since most households in Santa Julia have access to potable water (68%) and an indoor toilet (64%), food contamination were likely the vehicles of E. coli transmission because more than 50% of households do not have a refrigerator.

Rotavirus and more recently noroviruses are recognized as main causes of moderate to severe acute diarrhea episodes (ADE) in childrenor =5 years of age. Comparing epidemiologic and clinical features of norovirus to rotavirus ADE will aid in the decision-making process required to develop norovirus vaccines.Surveillance for ADE occurring in childrenor =5 years of age was implemented in the emergency department (ED) and ward of a large hospital in Santiago and Valparaiso, and in 4 outpatient clinics in Santiago. A stool sample was obtained within 48 hours of consultation for rotavirus detection by enzyme-linked immunosorbent assay and noroviruses by enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction. For ED and hospital rotavirus and norovirus ADE parents were instructed to monitor clinical findings associated with severity until the end of the episode. The 20-point Vesikari score was used to determine disease severity.Between July 2006 and October 2008 rotavirus and noroviruses were detected in 331 (26%) and 224 (18%) of 1913 ADE evaluated. The proportion of rotavirus-positive samples in hospital ward, ED, and outpatient clinic was 40%, 26% to 30%, and 13% compared with 18%, 17% to 19%, and 14% for noroviruses. Mean age and 25%-75% interquartile interval of children with rotavirus and norovirus ADE were remarkably similar, 15.6 months (9-20), and 15.5 months (9-19), respectively. Rotavirus cases displayed an autumn-winter peak followed 2 to 3 months later by the norovirus peak. The mean (interquartile) for the Vesikari score was 12.9 (11-15) and 11.9 (9-14.5) for rotavirus (N = 331) and norovirus (N = 224) ADE, respectively, P = 0.003. Compared with norovirus, rotavirus ADE were more common in the 11 to 16 severity score interval (P = 0.006), had a higher maximum stool output in a given day (P = 0.01) and more frequent fever (P0.0001). Duration of diarrhea, presence, duration and intensity of vomiting, and intensity of fever did not differ between viruses. Mixed rotavirus and norovirus infections were uncommon (1%) and not clinically more severe. Clinical severity of ADE in young infants was similar for rotavirus and lower (P = 0.03) for noroviruses compared with older children.Noroviruses are a significant cause of moderate to severe endemic ADE in Chilean children. Although significantly less severe than rotavirus as a group, most norovirus episodes were moderate to severe clinically. An effective norovirus vaccine would be of significant additional benefit to the current rotavirus vaccine in decreasing disease burden associated with ADE.

Se revisan y actualizan aspectos clínicos y epidemiológicos de las infecciones por Escherichia coli productora de shigatoxina (STEC), y el síndrome hemolítico urémico (SHU). Se incluyen resultados de una vigilancia de SHU en 14 centros centinelas (2000-2002), que mostró una incidencia promedio de 3,4 casos por 100.000 niños, 78%) en el grupo de 6 a 48 meses. Esta vigilancia reflejó una situación endémica, con aumento en verano. Se analiza la observación clínica protocolizada de 119 pacientes con SHU hospitalizados en la Región Metropolitana (RM) (1988 y 2002). Edad promedio: 16 meses. El 578%> tenía diarrea con sangre, 9%> no tenía diarrea previa, 60%> recibió antibacterianos, 72%> presentó oligoanuria y 53%> necesitó diálisis. El 31%o tuvo compromiso de conciencia y 15%o presentó convulsiones. Letalidad 3%. Se analizan brotes de STEC asociados a alimentos ocurridos en la RM en el hogar (2), un jardín infantil (1) y en un servicio de neonatología (1). Finalmente, se entregar recomendaciones para el manejo clínico y prevención, se revisan los criterios diagnósticos, nuevas estrategias terapéuticas y progresos en el desarrollo de vacunas.

Background: Acute bacterial meningitis (ABM) is a serious disease that needs rapid diagnosis for an accurate treatment. The most important etiological agents are: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b. Overall pathogen detection rate in patients with ABM in Chile is 83%. Aim: To evaluate a Polymerase Chain Reaction (PCR) protocol for simultaneous detection of several pathogens in patients with ABM. Material and methods: We designed and evaluated a multiplex PCR protocol for simultaneous specific genes identifications of S pneumoniae (¡ytA and ply genes), N meningitidis (ctrA, crgA) and H influenzae (bexA) in cerebrospinal fluid (CSF) samples from pediatric patients with suspected diagnosis of ABM. Sensitivity, specificity and minimum detection levels of DNA were determined. Amplifications ofrDNA 16S gene was done to confirm extraction of bacterial DNA. Results: Ninety nine CSF samples were studied, 90 from children with fever and negative CSF culture, and 9 from ABM and positive culture patients. The PCR protocol had a sensitivity of 89%, specificity of 100%, positive predictive value 100% and negative predictive value 99%. Conclusions: We observed a high concordance (89%) between bacteriological cultures and the PCR protocol results. This diagnostic tool could increase identification of agents in specific settings such as patients previously treated with antibiotics

Background: Shigella spp is a frequent cause of diarrhea in children. Antimicrobials decrease the duration of diarrhea and pathogen excretion. However, the increasing resistance limits their therapeutic value. Aim: To study Shigella serotype distribution in the Metropolitan Region in Chile, and its relationship with severity of disease, antimicrobial resistance pattern and clonality. Material and methods: During summer 2004-2005, stool samples from children with diarrhea were collected in Cary Blair transpon medium and cultured. Shigella isolates were serotyped using monoclonal and polyclonal commercial antibodies. In vitro activity of ampicillin, amoxicillin/clavulanic acid, chloramphenicol, cotrimoxazol, nalidixic acid, ciprofloxacin, ceftriaxone and azythromycin was determined by minimal inhibitory concentration (MIC). Clonality was studied by pulsed-field gel electrophoresis (PFGE) using Xbal as restriction enzyme. Results: One hundred thirty nine Shigella strains were isolated (77 S sonnei and 62 S flexneri). S sonnei and S flexneri 2a serotypes were responsible for 95% of episodes. Children aged 2-4 years, showed a greater incidence of Shigella infections and 77% of episodes were treated on an ambulatory basis. High resistance levels were observed for ampicillin, cotrimoxazole, amoxicillin-clavulanic acid and chloramphenicol (67%, 60%, 56% and 45%, respectively). We found 11 resistance patterns and 61,2% of strains were multiresistant. There were multiple clones without a strict relationship with resistance patterns. Conclusions: Shigella infections in Metropolitan Region in Chile are associated to a restricted number of serotypes, representing a clonal expansion associated to different antimicrobial resistant patterns

The frequency of astrovirus infection in 456 Chilean children with diarrhea was determined by enzyme-linked immunosorbent assay, reverse transcriptase PCR, and cell culture. Astrovirus was detected in 16.5% of rotavirus-negative and 7% of rotavirus-positive samples obtained from emergency rooms or hospitals and in 11% of samples from day care centers. HAst-1 was the predominant serotype identified.

Background: Cefpodoxime is a new antimicrobial in the Chilean market, recommended for treatment of respiratory and urinary tract infections. Aim: To study the susceptibility of common pathogens isolated from Chilean patients to cefpodoxime and other antimicrobials. Material and methods: The in vitro activity of cefpodoxime, expressed as Minimal Inhibitory Concentration, was studied in 331 S pneumoniae, H influenzae, M catarrhalis, E coli, S aureus and S pyogenes strains, isolated between 2000 and 2004 from respiratory, urinary and soft tissue infections, respectively. Results: Eleven percent of S pneumoniae isolates were resistant to penicillin, 11% were resistant to cefuroxime and 10% to cefpodoxime. All H influenzae isolates were susceptible to cefpodoxime. No H influenzae isolates were resistant to second or third generation cephalosporines. Four percent of H influenzae isolates were resistant to ampicillin by ß-lactamase production. In contrast 81% of M catarrhalis strains were resistant to ampicillin. Six percent of E coli isolates were resistant to cefpodoxime, 9% to cefuroxime, 11% to cefadroxile and 50% to ampicillin or trimethoprim/sulphamethoxazole. Cefpodoxime was the most active antimicrobial against S pyogenes. Conclusions: Cefpodoxime, recently introduced in Chile, is a good alternative for the treatment of common respiratory and urinary tract infections

Variations in antibiotic resistance patterns were studied among 178 Shigella strains isolated from 1997 to 2001 in children less than five years of age with acute diarrhea from Colina, a semi-rural community in Santiago, Chile. The minimal inhibitory concentration of several commonly used antibiotics was determined by the agar dilution method. Shigella strains showed high rates of resistance to ampicillin (82%), cotrimoxazole (65%), tetracycline (53%), and chloramphenicol (49%). Furthermore, 51% of the strains showed resistance patterns to multiple antibiotics. Only 9% of the strains were resistant to amoxicillin-clavulanic acid and no resistance was observed to ciprofloxacin, nalidixic acid, or cefotaxime. Continuous monitoring of resistance patterns in Shigella is essential for establishing and updating guidelines for antibiotic treatment in shigellosis.

More than one billion diarrhea episodes occur every year among children younger than 5 years of age in socioeconomically developing countries causing 2 to 2.5 million deaths. More than twenty viral, bacterial, and parasitic enteropathogens are currently associated with acute diarrhea. Rotavirus and diarrheagenic Escherichia coli are the most common pathogens responsible for acute diarrhea episodes in children; Shigella spp., Salmonella spp, Campylobacter jejuni/coli, Vibrio cholerae, Aeromonas spp, and Plesiomonas spp. occur more commonly in poorer areas and infections caused by protozoa and helminthes occur mainly in areas where environmental sanitation is significantly deteriorated. Initial clinical assessment of a child with diarrhea should focus on obtaining an accurate evaluation of hydration and nutritional status. Assessment of stool characteristics (e.g., liquid non-bloody stools vs. dysenteric or bloody stools) is a key feature in determining potential pathogens causing an acute diarrhea episode. Diagnostic guidelines are discussed in the article. The major therapeutic intervention for all individuals with diarrhea consists of fluid and electrolyte therapy. When antimicrobial therapy is appropriate, selection of a specific agent should be made based upon susceptibility patterns of the pathogen or information on local susceptibility patterns. Current guidelines for administering appropriate antimicrobial treatment are provided in the article. Preventive measures include careful personal hygiene, especially promotion of hand washing. Immunizations currently or soon to be available for Salmonella serotype Typhi, cholera prevention, and rotavirus are discussed.

Background: Foodborne diseases are becoming an important cause of morbidity in Chile. In the Metropolitan Region of Chile, the Environmental Health Service started a surveillance program for foodborne diseases in 1994. In 2000, this program was complemented with an etiologic study of individuals involved in outbreaks. Aim: To report the incidence of foodborne outbreaks in the Metropolitan Region of Chile and its causative agents. Results: One hundred ninety outbreaks of foodborne diseases were reported in 1999 and 260 in 2000. The Southern Metropolitan health service had the higher incidence rates (7.5 in 1999 and 8.2 in 2000). The mean attack rates were 25% in both periods, affecting 1248 individuals in 1999 and 1774 in 2000. In 18% of outbreaks, a pathogen was identified; the most frequent agents were Salmonella Spp, Staphylococcus aureus and Shigella. In 15% of subjects, the cause was histamine or chemical agents. In the rest of the cases, the cause was not identified. The foods with higher risk of causing foodborne diseases were hot prepared dishes, home made goat cheese and meats. Conclusions: The incidence rates of foodborne disease in Metropolitan Area of Chile are high and maybe underestimate, only in a low rate of outbreaks was possible to have samples for etiologic studies. For a better understanding of this problem, timely notification of foodborne diseases must be encouraged and educational campaigns about the proper manipulation of food items must be implemented (Rev Med Chile 2002; 130: 495-501)

En el transcurso de los años hemos sido testigos de un creciente problema de resistencia antimicrobiana, fenómeno que involucra cada día mayor número de cepas, nuevas especies y nuevos mecanismos. En noviembre de 1997 iniciamos una red de vigilancia de resistencia antimicrobiana PRONARES (Programa Nacional de Resistencia), en diferentes hospitales del país, que trabajando un protocolo común (20 cepas por síndrome clínico por mes) y utilizando un programa computacional WHONET (diseñado para vigilancia), nos permitiera detectar y monitorear el problema de la resistencia bacteriana en Chile. Los resultados del primer semestre de este año reportan 5.251 cepas de diferentes síndromes clínicos. En ITU, Escherichia coli (1.088 cepas) demostró alta susceptibilidad a todos los antimicrobianos, Klebsiella (1.000 cepas) demostró un perfil de resistencia más elevado, en cepas de Enterococcus spp se observó 30% de resistencia a ciprofloxacina y 2% a nitrofurantoína. Entre 899 cepas procedentes de infecciones invasoras, Staphylococcus aureus (555 cepas), mostró elevado perfil de resistencia a cloxacilina 40% superior -40%- (21%) al observado en cepas aisladas de piel y tejidos blandos (550). Shigella spp, (137 cepas) presentó 80% de resistencia a ampicilina y 32% a cloranfenicol; ciprofloxacina y furazolidona demostraron muy buena actividad in vitro frente a este enteropatógeno. Al comparar cepas nosocomiales y de la comunidad, las primeras mostraron un perfil de mayor resistencia. Mantener una red nacional de vigilancia de resistencia se hace cada vez más necesario para orientar el uso adecuado de antibacterianos y evitar así que el fenómeno aumente

Background: PRONARES (Programa Nacional de Vigilancia de Resistencia) is a national surveillance program for antimicrobial susceptibility, focused in different syndromes and among these, urinary tract infections. The work is done in a laboratory net that uses common protocols and whose data are centrally analyzed using the WHONET program. Aim: To analyze the pattern of antimicrobial susceptibility of agents causing urinary infections in children in the period 1997-1999. Material and methods: In the study period, 5,525 strains were analyzed. Of these, 2,307 came from pediatric patients (1,495 hospitalized and 803 ambulatory). Results: The most common causative agent was E. coli in 74,2% of cases, followed by Klebsiella spp in 8,2% and other agents in a lower frequency. Of E. coli strains, 74% were resistant to ampicillin, 52% to clotrimoxazole and 30% to first generation cephalosporins. These strains were sensitive to second and third generation cephalosporins, aminoglycosides, ciprofloxacin and nitrofurantoin. Strains from nosocomial or community infections had similar antimicrobial susceptibility. Klebsiella spp had a high rate of antimicrobial resistance (over 40%), that was even higher among nosocomial strains. It was 90% susceptible to ciprofloxacin and 100% to imipenem. All centers from which strains came had a similar pattern of susceptibility, with the exception of a pediatric center that had significantly higher resistance levels. Conclusions: The current therapeutic recommendations for urinary tract infections in children caused by E coli, are still pertinent, but the use of first generation cephalosporins must be cautious. The treatment of Klebsiella spp requires an individual antibiogram (Rev Méd Chile 2001; 129: 877-885).

Background: There is a high prevalence of infection by Enterohemorrhagic Escherichia coli (EHEC) and patients with hemolytic uremic syndrome (HUS) in Argentina. Aim: To study cattle and pigs as a possible reservoir of EHEC in Argentina. Material and methods: One hundred two healthy animals (68 cattles and 31 pigs) from a livestock in Argentina, were studied. Stool samples were obtained with a rectal swab. The strains were identified by DNA hybridization with specific gene probes detecting Shiga-like toxin 1 and 2 (Stx1, Stx2), and hly gen related to fimbrial adhesin-associated plasmid. EHEC strains were serogrouped using comercial antisera. Results: EHEC was isolated from 30 out of 68 bovines cultures (44.1%) and from 25 out of 31 pigs (58.1%). Isolates carrying genes codifying both Stx1 and Sxt2, were observed in 50% of cattle and 63.9% of pigs. The gene which codifies for hemolysin (associated to fimbrial adhesin) was observed in about 41% of EHEC isolates. Strains belonging to serogroups O26, O111, and O157 were isolated from cattle, and O111, and O157 from pigs. Conclusions: The high percentage of EHEC in both cattle and pigs and the presence of human infection-associated serogroups, suggests that these animals are a reservoir of EHEC associated with disease in humans (Rev Med Chile 2000; 128: 1335-41).

Backgrund: Chlamydia trachomatis is one of the most common identifiable infectious agents in neonatal conjunctivitis. It also causes pneumonitis, that is preceded by conjunctivitis in one third of cases. Aim: To asses the prevalence of Chlamydia trachomatis in newborns with conjunctivitis. Patients and methods: In 162 newborns, coming from 14 Primary Health Centers from Santiago de Chile, C. trachomatis was detected by indirect fluorescence and two polymerase chain reaction (PCR 1 and 2), wich amplified different sequences from the common endogenous plasmid. Those patients with positive indirect fluorescence and PCR 2 were definedas infected: Results: The prevalence of C. trachomatis was 8%, and the distribution of the positive cases was similar in the different Health Centers. Other isolates were: S. aureus (9.8%), S. pneumoniae (8%), S. viridans (6.2%) y H. influenzae (5.5%). Conclusions: The prevalence of C. trachomatis in neonatal conjunctivitis in Chile is similar to that of developed countries. Therefore, C. trachomatis should be considered in the election of antimicrobials for the treatment of neonatal conjunctivitis, to avoid ocular and respiratory complications. (Rev Méd Chile 2000; 128: 758-65).

In Latin America, Shigella and shiga toxin-producing Escherichia coli are the two leading agents in the cause of bloody diarrhea. The already high and increasing antimicrobial resistance of Shigella also is a significant problem. Shiga toxin-producing E. coli is an emerging disease with life-threatening complications: hemolytic uremic syndrome. Although E. coli O157:H7 remains the most commonly recognized serotype, recently emerging, non-O157 bacteria may be the cause of a similar spectrum of disease in humans.

122SHIGELLA OUTBREAK IN AN ELEMENTARY SCHOOLIn autumn 1996, children from an elementary school in Santiago wereaffected by an outbreak caused by Shigella sonnei. Initially 35 children out of350 beneficiaries of the feeding program got sick. However, in the next five days,189 new cases appeared. Sixty eight patients submitted stool samples for culture(65 children and 3 food handlers); 20.5% of stool cultures from the childrenwere positive for S. sonnei, and all samples from food handlers were negative.The presentation of the outbreak states a toxiinfection due to S. sonnei, whichprobably started by ingestion of contaminated food (rate of primary attack 10%)and then person to person transmission (rate of secondary attack 16.9%). Tocontrol the outbreak, the personal sanitation rules were enforced as well asthose concerning the environment with educational lectures to all the schoolcommunity and with sanitary in situ control. Five days after beginning the firstcase, trimethoprim-sulpha was administered to only those symptomatic casesduring five days.Key words: Outbreak; Diarrhea; Shigella sonnei; School children.EPIDEMIOLOGIA

Background: As sanitary and economic conditions improve, the prevalence of antibodies to hepatitis A is now significantly lower. Aim: To evaluate the prevalence of hepatitis A virus antibodies in healthy Chilean adults. Material and methods: Antibodies to hepatitis A virus were measured, using a commercial ELISA assay, in 215 voluntary blood donors (163 male, aged 19 to 30 years old) and 295 medical students and health personnel (156 male, aged 19 to 39 years old), residing in Valdivia, Chile. Results: Antibodies against hepatitis A virus were found in 68,2% of the total sample (351/510). Ninety percent of flood donors and 54% of health personnel and students were positive (p

Background: The computer program WHONET generates a common database to analyze local or general antimicrobial resistance of bacteria. A surveillance of agents causing urinary tract infections in Chile has been performed using this program. Aim: To report the results after 12 months of urinary tract infection agent surveillance. Material and methods: Since November, 1997, a surveillance of in vitro antimicrobial resistance, using agar diffusion techniques, has been performed in 20 to 40 bacterial strains per month, isolated from 11 hospitals in the country. Results have been analyzed using WHONET program. Results: In first 12 months, 3144 strains, 1625 coming from outpatients, have been studied. Seventy four percent of isolated strains were E coli, 19% were other enterobacteria, 4.1% were non fermenting bacilli and 2.1% were Gram (+) cocci. Sixty five percent of E coli strains were resistant to ampicillin, 11% to cefazolin, 2.5% to cefuroxime, 19% to ceftriaxone, 9% to ceftazidime, 4.2% to gentamicin 1.3% to amikacin, 5.6% to ciprofloxacin, 8.4% to grepafloxacin, 4.3% to nitrofurantoin and 43% to trimeproprim/sulphamethoxazole. Eighty two percent of other enterobacteria strains were resistant to ampicillin, 45.5% to cefazolin, 33.5% to cefuroxime, 26.6% to ceftriaxone, 21.5% to ceftazidime, 30.3% to gentamicin 17.2% to amikacin, 21% to ciprofloxacin, 16.3% to grepafloxacin, 48.2% to nitrofurantoin and 44.6% to trimeproprim/sulphamethoxazole. There were differences in betalactamic resistance among hospitals. Conclusions: Noteworthy is the high resistance rates to third generation cephalosporins, evidenced when the new cutoff values for E coli and Klebsiella spp are used. This national surveillance provides updated information on antimicrobial resistance of agents causing urinary tract infections.

e good to mcnitore antimicrobial resistance and oreva'en? sero'ypes. To desc'"beprevalence o~ resistant isolates of S. pneumoniae among children attending day ca'e centers and their most prevalentserotyoes, samples o~ nasopharyngeal secretions were obtained a-d cultured in sheep blooc cgar with o' withoutgentamicin 5 (ig/rri a' 37° C in c 5% CO

Yersinia enterocolitica is a common cause of endemic enteric infections in industrialized countries of Europeand in the USA. Little information on Yersiniosis is available from South America. This study was intended to deter-mine the incidence and clinical pattern of enteric infections caused by Y. enteroco/itica in three cohorts of children,the first one of 360 subjects under 4 years of age followed along a two year period, and another two cohorst madeof 144 newborn infants each, which were followed from april 1987 throughout february 1990 and from October1989 throughout february 1990 respectively, all from a low socio-economic status neighborhood at Santiago, Chile,Children were prospect ively surveilled by bi-weekly home visits. Two stool samples were obtained during each diarrhealepisode and from matched asymptomatic control subjects. From february 1987 throughout January 1990, 1 795diarrheal episodes were recorded and studied. Incidence of Y. enterocolitica was 1.4% among patients with diarrheaand 0.3% among 1 780 controls 14 days) ocurred in 11.5% of thepatients. All cases were treated as outpatients and their outcome was good. Most isolated Y. enterocolitica strainsbelonged to serotype 0:3, byotype 4 (73%); other isolated serotypes included 0:7.8, 0:10 and 0:6. We did notobserve a clearly defined seasonal predominance although 50% of cases ocurred in winter months. Y. enterocotiticawas an infrequent cause of acute diarrhea (1.4%) in Santiago. Because it was frequently associated with persistentdiarrhea, an adequate work up for this organ ism using selective media should be considered in all cases with diarrhealdisease,(Keywords: Yersinia enterocolitica, enteric infection, diarrhea.)

To prepare a field site for evaluating preventive interventions against endemic shigellosis, the authors followed prospectively a cohort of 360 children (90 each of children aged 0-11, 12-23, 24-35, and 36-47 months) in Santa Julia, a low socioeconomic area in Santiago, Chile, from November 1986 through April 1989 with twice weekly household visits for diarrheal disease; infants replaced children who reached 60 months of age. Coprocultures on 2 consecutive days from children with diarrhea and from age-matched controls within the cohort were cultured for Shigella. Bacteriologic surveillance was also maintained in the health center and children's hospital serving Santa Julia. In this community, where all households had access to potable water (68% inside) and all but 3% had access to a toilet, but where there was marked crowding, the overall incidence of diarrheal disease in the cohort was low (2.26 episodes/12 child months of observation in children aged 0-11 months and 2.09 in those aged 12-23 months), yet Shigella infections were common. Shigella accounted for 10% of diarrheal episodes in the cohort (vs. 3.2% isolation rate in controls, p less than 0.0001). The incidence of shigellosis in children aged 12-47 months was 0.16 cases per 12 child months of observation; in the first 5 years of life, a child had a 67% chance of experiencing shigellosis. Shigella sonnei, Shigella flexneri 2a, and S. flexneri 6 caused greater than 79% of the infections. Shigella occurred more often in hospitalized cases of diarrhea than in age-matched cases detected in the health center or by household surveillance (p less than 0.0001). An initial episode of Shigella diarrhea did not diminish overall the risk of subsequent shigellosis but did confer 72% protection (p = 0.05) against illness due to the homologous serotype. The high rate of both S. sonnei and S. flexneri shigellosis in a population with a low background rate of diarrhea makes Santa Julia an appropriate site for assessing the efficacy and effectiveness of measures to reduce Shigella infections.

A total of 24 pediatric patients with a diagnosis of meningitis, confirmed by positive CFS culture, were enrolled in the study. All patients received ceftriaxone in different doses. No difference in clinical outcome was found between the patients who received ceftriaxone twice a day and the 11 who received the drug as a single daily dose. The latter dosage proves to be preferable. The therapeutic outcome in this series of patients was 22 cured and 2 failures. Bacteriological and pharmacokinetic findings are discussed.

A total of 516 Escherichia coli strains randomly isolated from coprocultures of 154 Chilean children with diarrhea and 66 controls were examined with DNA probes and tested for adherence to HEp-2 cells. Three adherence patterns were distinguished, localized, true diffuse and "aggregative." Enteropathogenic E. coli (EPEC) were detected by EPEC adherence factor probe among 86 of the 372 isolates (23%) from patients with diarrhea vs. 14 of 144 (10%) strains from controls (P less than 0.0002). Of 95 strains that manifested localized adherence, 97% were EPEC adherence factor probe-positive; thus the HEp-2 assay may serve as an alternative to the probe in identifying EPEC adherence factor-positive EPEC. True diffuse adherence was not associated with diarrhea. In contrast the aggregative pattern appears to signify a new, distinct class of diarrheagenic E. coli (enteroadherent-aggregative E. coli). The aggregative pattern was found in only 3 of 27 enterotoxigenic, 0 of 4 enteroinvasive, 0 of 2 enterohemorrhagic and 2 of 86 EPEC strains but in 84 of 253 probe-negative strains (P less than 0.00001) from patients with diarrhea; in comparison only 20 of 134 probe-negative strains from controls were aggregative E. coli (P less than 0.00001 vs. probe-negative strains from diarrhea patients).

The high spreading rate of Haemophilus influenzae serotype b (Hi b) infections in children has been alreadyestablished. Rifampin prophylaxis is recommended in household contacts under 4 years of age. To define the localepidemic logical situation, 31 patients with invasive Hi b disease from two pediatric hospitals of Santiago Chile werestudied (24 had meningitis, 3 facial cellulitis, 1 necrotic pneumoniae and 3 pleuropneumonia, one of them withpericarditis), looking for pharingeal carriers of Hi b among household contacts: 18% of children and 5.9% of adultscontacts were colonized with the microorganism. Secondary disease was also detected in one household contactaged 7 months. Carriers were treated with oral rifampin 20 mg/kg per day (maximun dose 600 mg per day) during 4days, which resulted in erradication of the carrier state in all cases. Twelve percent of Hi b strains were ampiciUin-resistant and 4% showed ampicillin-chloramphenicol combined resistance among index cases. All strains isolatedfrom carriers were susceptible to both drugs.(Key words: bacterial infections, Haemophilus influenzae type B, household contacts, carriers, erradication,rifamycins, rifampicin.)

RESUMEN Se estudian 51 lactantes con infeccion enteralpor ECEP. Por metodo doble ciego se sometlana tres esquemas terapeuticos: un grupo de 16 lac-tantes recibio placebo consistente en glucosa; aotro grupo de 16 lactantes se le administro Neo-micina y un tercer grupo de 19 lactantes fue tra-tado con lactobacilos. Al cabo de 7 dias de trata-miento se ejectuaron evaluaciones cllnicas y bac-terioldgicas. El andlisis estadistico de los resultadosdemostro ciaras ventajas del itso de Neomicina eninjeccidn enteral por ECEP.SUMMARY 51 infants with diarrheal disease caused by patho-genic E. coli were studied with a double blind method.A group of 16 infants received dextrose as a place-bo; a second group of 16 received Neomycin and thirdgroup of patients was treated with lactobacillus; clinicaland bacteriological controls were performed at the se-venth day of treatment. The statistical analysis conclu-ded a clear advantage in the use of Neomycin in enthericinfections by E. coli. BlBLIOGRAFfA 1.— Rossenstein, B. Salmonellosis in infants and chil-drens. J. of Fed. 70-1-1957.2.— Prado, Valeria; Mimica, Igor; Donoso, Edo. Etiolo-gia bacteriana de la diarrea aguda del lactante, apor-tes de la Inmunofluorescencia. Estudio de Sensibi-lidad in vitro de los bacterios estudiados. (CongresoNacional de Pediatria 1973).3.— Alexander L G. Thrush bowel infection existenceincidence, prevention and treatment, particularly bya lactobacillus acidophillus preparation. Curr. Med.Drugs 8: 3-11 Die. 1967.4.— Tramer Inhibitory effect of Lactobacillus. Nature2: 11-204-5 July 9, 1966.5.— Pene P. et. al. The colibacillus combination in thetreatment of diarrhea in adults childrens and in-fants, Sem 40 p. Paris 42-241 4 20 Jan. 1966.146

International audience; Background: Shigellosis or bacillary dysentery, an acute bloody diarrhoea, is a major public health burden in developing countries. In the absence of prompt and appropriate treatment, the infection is often fatal, particularly in young malnourished children. Here, we describe a new diagnostic test for rapid detection, in stool, at the bedside of patients, of Shigella flexneri 2a, the most predominant agent of the endemic form of the disease.Methodology/principal findings: The test is based on the detection of S.flexneri 2a lipopolysaccharide (LPS) using serotype 2a-specific monoclonal antibodies coupled to gold particles and displayed on one-step immunochromatographic dipstick. A concentration as low as 20 ng/ml of LPS is detected in distilled water and in reconstituted stools in under 15 minutes. The threshold of detection corresponds to a concentration of 5x10(7) CFU/ml of S. flexneri 2a, which provides an unequivocal positive reaction in three minutes in distilled water and reconstituted stools. The specificity is 100% when tested with a battery of Shigella and unrelated strains, in culture. When tested in Vietnam, on clinical samples, the specificity and sensitivity were 99.2 and 91.5%, respectively. A decrease of the sensitivity during the evaluation on stool samples was observed after five weeks at room temperature and was due to moistening of the dipsticks caused by the humidity of the air during the fifth week of the evaluation. This drawback is now overcome by improving the packaging and providing dipsticks individually wrapped in waterproof bags.Conclusion: This simple dipstick-bases test represents a powerful tool for case management and epidemiological surveys.