Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children.

BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.

[Mucosal complication of cutaneous leishmaniasis]. / Complicación mucosa de la leishmaniasis cutánea.

A 74-year-old man from the rural area of Caicedonia, Valle del Cauca Province, was diagnosed with uncontrolled hypertension, stage IV chronic renal failure and severe anemia. Fifteen years earlier, while living in Guaviare Province, he was diagnosed with leishmaniasis-with lesions located on the right upper and lower eyelids, left auricle and limbs. At that time, he received an incomplete treatment with antimonials. The patient had experienced 8 years of progressive mucosal lesions located in the upper lip, nasal mucosa and right upper and lower eyelids (figure 1). A histopathological diagnosis of leishmaniasis was made and confirmed by polymerase chain reaction (figure 2). Treatment with antimonials (Glucantime) was contraindicated due to the patient's comorbidities. Inpatient supervised treatment with miltefosine (Impavido 50 mg capsules) was initiated according to the national guidelines of 1.8 mg/kg/day for 28 days. Clinical follow up and routine laboratory tests (creatinine, BUN, liver function tests and complete blood counts) were done during and after treatment; no complications were reported. Medical follow up was continued until the Internal medicine, ophthalmology, and plastic surgery consultations were provided for subsequent management of the pathology. Mucocutaneous leishmaniasis is a serious preventable complication of cutaneous leishmaniasis. This case illustrated a failure in opportune diagnosis and treatment of this disease as a consequence of an inadequate leishmaniasis control program. The case indicated the effectiveness of miltefosine as a therapeutic option in patients for whom antimonial treatment is contraindicated.

Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia.

American cutaneous leishmaniasis (ACL) has been characterized as a zoonotic disease. However, peridomestic and domestic transmission have been recorded in at least nine countries in Central and South America. The present study was undertaken to identify the etiologic agent of a peridomestic epidemic of ACL in the Department of Tolima, Colombia. Leishmania isolates were obtained during the diagnosis of 56 patients with ACL who consulted the local leishmaniasis control program in three municipalities in Tolima. Species were identified using monoclonal antibodies and isoenzyme electrophoresis. A total of 53 (94.6%) of 56 isolates were identified as Leishmania (Viannia) guyanensis. Three isolates (5.4%) were identified as L. (V.) panamensis. Leishmania (V.) guyanensis is the probable etiologic agent of the largest epidemic of cutaneous leishmaniasis recorded in Colombia. This species has not previously been reported outside the Amazon and southeastern regions of Colombia, and has not been described in the peridomestic setting or linked with an epidemic.

[Antimicrobial resistance in gram negative bacteria isolated from intensive care units of Colombian hospitals, WHONET 2003, 2004 and 2005]. / Resistencia a antimicrobianos de bacilos gram negativos aislados en unidades de cuidado intensivo en hospitales de Colombia, WHONET 2003, 2004 y 2005.

INTRODUCTION: Surveillance systems play a key role in the detection and control of bacterial resistance. It is necessary to constantly collect information from all institutions because the mechanisms of bacterial resistance can operate in different ways between countries, cities and even in hospitals in the same area. Therefore local information is important in order to learn about bacterial behaviour and design appropriate interventions for each institution. Between January 2003 and December 2004, the Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) developed a surveillance project in 10 tertiary hospitals in 6 cities of Colombia. OBJECTIVES: Describe the trends of antibiotic resistance among the isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomona aeruginosa, Acinetobacter baumannii and Enterobacter cloacae, five of the most prevalent nosocomial Gram negative pathogens. MATERIALS AND METHODS: The susceptibility tests were performed by automated methods in 9 hospitals and by Kirby Bauer in 1 hospital. Antibiotics with known activity against Gram negatives, according to the Clinical Laboratory Standards Institute guidelines, were selected. The laboratories performed internal and external quality controls. During the study period, the information was downloaded monthly from the databases of each microbiology laboratory and sent to CIDEIM where it was centralized in a database using the system WHONET 5.3. RESULTS: The high resistance rates reported especially for A. baumannii, evidenced the presence of multidrug resistant bacteria in both ICUs and wards at every studied institution. CONCLUSIONS: The creation of a national surveillance network to improve our capabilities to detect, follow up, and control the antibiotic resistance in Colombia is urgently needed.

Resistencia a antimicrobianos de bacilos Gram negativos aislados en unidades de cuidado intensivo en hospitales de Colombia, WHONET 2003, 2004 y 2005 / Antimicrobial resistance in Gram negative bacteria isolated from intensive care units of Colombian hospitals, WHONET 2003, 2004 and 2005

Introducción. Los sistemas de vigilancia son una pieza clave para la detección y control de la resistencia bacteriana. Es indispensable recolectar constantemente la información de cada institución por la variabilidad existente entre países, ciudades y hospitales frente a los mecanismos de resistencia bacteriana y así plantear intervenciones apropiadas para cada institución. De enero 2003 a diciembre de 2005, el Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) desarrolló un proyecto de vigilancia en un grupo de 10 hospitales de tercer nivel, en seis ciudades de Colombia. Objetivos. Presentar el comportamiento de Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii y Enterobacter cloacae, considerados los Gram negativos patógenos más relevantes en infección nosocomial, frente a antimicrobianos seleccionados. Materiales y métodos. Las pruebas de susceptibilidad se realizaron por métodos automatizados en 9 hospitales y por Kirby Bauer en un hospital. Se eligieron antibióticos con actividad reconocida contra Gram negativos, de acuerdo con las guías del Comité Nacional para el Control de Estándares en el Laboratorio Clínico (NCCLS). Los laboratorios realizaron control de calidad interno y externo. Mensualmente se recibió la información procedente del laboratorio de microbiología de cada institución y se centralizó en una base de datos en WHONET 5.3 en CIDEIM . Se realizó un análisis conglomerado de frecuencias y porcentajes de resistencia a antibióticos. Resultados. Los altos porcentajes de resistencia reportados en especial para A. baumannii, corroboraron la presencia de bacterias multirresistentes en las UCI en las instituciones participantes durante el periodo de estudio. Conclusiones. Es urgente crear una red nacional de vigilancia de la resistencia a antimicrobianos de los patógenos hospitalarios y de esta manera mejorar nuestra habilidad para detectar, supervisar y manejar la resistencia a antimicrob...

Introduction. Surveillance systems play a key role in the detection and control of bacterial resistance. It is necessary to constantly collect information from all institutions because the mechanisms of bacterial resistance can operate in different ways between countries, cities and even in hospitals in the same area. Therefore local information is important in order to learn about bacterial behaviour and design appropriate interventions for each institution. Between January 2003 and December 2004, the Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) developed a surveillance project in 10 tertiary hospitals in 6 cities of Colombia. Objectives. Describe the trends of antibiotic resistance among the isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomona aeruginosa, Acinetobacter baumannii and Enterobacter cloacae, five of the most prevalent nosocomial Gram negative pathogens. Materials and Methods: The susceptibility tests were performed by automated methods in 9 hospitals and by Kirby Bauer in 1 hospital. Antibiotics with known activity against Gram negatives, according to the Clinical Laboratory Standards Institute guidelines, were selected. The laboratories performed internal and external quality controls. During the study period, the information was downloaded monthly from the databases of each microbiology laboratory and sent to CIDEIM where it was centralized in a database using the system WHONET 5.3. Results. The high resistance rates reported especially for A. baumannii, evidenced the presence of multidrug resistant bacteria in both ICUs and wards at every studied institution. Conclusions. The creation of a national surveillance network to improve our capabilities to detect, follow up, and control the antibiotic resistance in Colombia is urgently needed.

[Ethics review committees for human research: the challenge of strengthening this process in Colombia]. / Comités de etica de investigación en humanos: el desafío de su fortalecimiento en Colombia.

INTRODUCTION: Ethics committees are a necessary resource to guarantee ethical integrity in human research; they must apply international standards in their ethical evaluation of research projects involving human subjects. OBJECTIVE: The ethics committees for human research of Colombia were characterized, and recommendations for strengthening them were formulated. MATERIALS AND METHODS: In 2003, 280 groups with research projects involving human subjects were selected from a list of research groups which form part of the science and technology network of Colciencias. (Colciencias is the Colombian national agency that promotes and funds science and technology.) Eighty percent (224) of the projects were associated with 40 institutions, consisting of universities, hospitals, and public or private research centers. Thirty of these institutions had at least one ethics committee for evaluating use of human subjects. A questionnaire was mailed to each of these Committees, requesting information concerning its their compostition, regulations, multidisciplinarity, plurality, representativity and independence. The World Health Organization's Operational Guidelines for Ethic Committees that Evaluate Biomedical Research (TDR/PRD/ETHICS/2000) was used as reference for the analysis. In 5 of the cities, supplemental information was obtained by direct discussions with members of the ethics committees. RESULTS: Twenty-six committees responded to the questionnaire. The results indicated that 47% of the committee members were physicians, but only 23% of the committees had representatives from the community. In 60% of the Committees, members were not independent from the organization in which it was based. Seventy percent had established operating procedures. Lack of national regulations and limited education in research ethics were mentioned as the main drawbacks in providing effective guidance. CONCLUSIONS: These observations led to the conclusion that national guidelines must be established for ethics committees that correspond to international standards. Committee members must be trained before accepting committee responsibilities. Finally, new committees must be created along with the improvement of the currently existing committees for reinforcing and promoting the importance of ethical integrity in research.

Comités de ética de investigación en humanos: el desafío de su fortalecimiento en Colombia / Ethics review committees for human research: the challenge of strengthening this process in Colombia

Introducción. Los comités de ética de investigación en humanos que aplican los estándares internacionales en la evaluación ética de proyectos de investigación son un recurso indispensable para garantizar la integridad ética de la investigación en humanos. Objetivo. El presente trabajo se propuso conocer las características de los comités de ética de investigación en humanos y sus necesidades con miras a su fortalecimiento en Colombia. Materiales y métodos. En el 2003, se seleccionaron 280 grupos de investigación en humanos de un listado de grupos de investigación que acudieron a la convocatoria del año 2002 de la Red de Ciencia y Tecnología de Colciencias. El 80 por ciento de estos grupos pertenecía a 40 instituciones entre universidades, hospitales y centros de investigación públicos y privados. Treinta de 40 instituciones tenían comité de ética. Se les envió un cuestionario que indagaba sobre la constitución, reglamentación, composición multidisciplinaria, pluralidad, representatividad e independencia de los comités. Las respuestas se analizaron utilizando como referencia las Guías operacionales para comités de ética de investigación biomédica (TDR/PRD/ETHICS/2000). Se complementó la información obtenida mediante discusiones con miembros de estos comités en cinco ciudades del país. Resultados. Veintiséis comités respondieron la encuesta. El 47 por ciento de los miembros eran médicos, 23 por ciento de los comités tenía un miembro representante de la comunidad, 40 por ciento tenía un miembro independiente, 70 por ciento tenía manual de operaciones. Mencionaron la necesidad de mejorar la constitución de los comités, la capacitación de sus miembros, la regulación y las guías nacionales. Conclusión. Es urgente que en Colombia se elaboren guías nacionales para los comités de ética de investigación basados en estándares internacionales, se capacite a sus miembros y se promueva la integridad ética de la investigación.

Actividad in vitro de ertapenem frente a entrobacterias provenientes de la comunidad en siete ciudades de Colombia / In vitro Activity of Ertapenem Against Community Isolates of enterobacteriaceae from Seven Cities in Colombia

Objetivo. Evaluar los perfiles de sensibilidad in vitro de ertapenem y comparar su actividad con la de otros antibióticos de uso clínico para Enterobacteriaceas de la comunidad en Colombia. Materiales y métodos. Estudio descriptivo en el cual se recolectaron aislamientos clínicos de Enterobacterias provenientes de la comunidad de once hospitales de siete ciudades de Colombia. Los aislamientos se probaron con diferentes antibióticos –incluido el ertapenem– mediante la técnica de microdilución en caldo y la utilización de suspensiones bacterianas según las recomendaciones vigentes del Clinical and Laboratory Standards Institute (CLSI). En un grupo de bacterias con fenotipo compatible con la producción de β-lactamasas de espectro extendido (BLEE), se realizó la prueba confirmatoria de BLEE de Vitek®.Resultados. Se recolectaron 448 cepas; las sitios de aislamiento más frecuentes fueron la piel y los tejidos blandos (48 por ciento), el tracto genitourinario (27 por ciento) y las secreciones intraabdominales (16 por ciento). La sensibilidad dle ertapenem en todos los aislamientos fue de 100 por ciento. Los otros antibióticos presentaron comportamientos variables para cada especie bacteriana. Se resalta que Escherichia coli presentó 26 por ciento de resistencia a las quinolonas. De los 10 aislamientos de E. coli y 5 de Klebsiella con fenotipo sugestivo de producción de BLEE, 4 y 2, respectivamente, se confirmaron como BLEE positivos mediante la prueba confirmatoria. Conclusión. Los aislamientos de infecciones adquiridas en la comunidad son adecuadamente inhibidas por el ertapenem. Existen bacterias resistentes a los diferentes antibióticos, excepto a los carbapenems. Se evidencia la presencia de cepas productoras de BLEE en la comunidad que son inhibidas adecuadamente in vitro por el ertapenem

Prevalence and characterization of extended-spectrum beta-lactamases in Klebsiella pneumoniae and Escherichia coli isolates from Colombian hospitals.

Gram-negative pathogens harboring extended-spectrum beta-lactamases (ESBL) are widely prevalent in Latin America, but little is known about their prevalence in Colombia. A network of 8 tertiary care hospitals in Bogotá, Medellín, and Cali, Colombia, was formed in January 2002 to determine the prevalence of ESBL-producing Klebsiella pneumoniae and Escherichia coli. We characterized and established the molecular epidemiology of ESBLs from these hospitals. Data from 1074 E. coli and 394 K. pneumoniae isolates were obtained from hospital laboratories during 6 months. Isolates resistant to third-generation cephalosporins or aztreonam were sent to a central laboratory. The prevalence of strains with this phenotype was 32.6% in K. pneumoniae and 11.8% in E. coli from the intensive care units, with slightly lower percentages from wards. Although TEM and SHV enzymes were present, the dominant class was CTX-M. Molecular typing of chromosomal DNA showed that most strains were not clonal.