Abstract INTRODUCTION Lateral flow assay is an advanced method useful in the early diagnosis of cryptococcal meningitis. We aimed to compare two commercial tests for cryptococcal capsular antigen in the sera of asymptomatic patients with human immunodeficiency virus in Barranquilla, Colombia. METHODS Thawed (n=162) previously collected serums (2016-2019) were processed using IMMY and Dynamiker cryptococcal antigen lateral flow assay. RESULTS Compared to IMMY’s results, Dynamiker’s sensitivity, specificity, positive predictive value, negative predictive value, and kappa index were 100%, 89.9%, 48.3%, 100.0%, and 0.61, respectively. CONCLUSIONS The Dynamiker test had excellent sensitivity, acceptable specificity, and a low detection threshold for cryptococcal antigen in the tested samples.

Abstract INTRODUCTION: The average annual incidence of cryptococcosis in Colombia is 0.23 cases per 100,000 inhabitants in the general population, and 1.1 cases per 1000 in inhabitants with Acquired Immune Deficiency Syndrome (AIDS). In addition, the causal fungus has been isolated from the environment, with serotypes A-B and C in different regions. This study aims to determine the genetic association between clinical and environmental isolates of C. neoformans/C. gattii in Colombia. METHODS: Multilocus sequence typing (MLST) was used to identify possible clones, providing information about the epidemiology, ecology, and etiology of this pathogen in Colombia. RESULTS: A total of 110 strains, both clinical (n=61) and environmental (n=49), with 21 MLST sequence types (ST) of C. neoformans (n=14STs) and C. gattii (n=7STs) were identified. The STs which shared clinical and environmental isolate sources were grouped in different geographical categories; for C. neoformans, ST93 was identified in six departments, ST77 in five departments; and for C. gattii, ST25 was identified in three departments and ST79 in two. CONCLUSIONS: High genetic diversity was found in isolates of C. neoformans/gattii by MLST, suggesting the presence of environmental sources harboring strains which may be sources of infection for humans, especially in immunocompromised patients; these data contribute to the information available in the country on the distribution and molecular variability of C. neoformans and C. gattii isolates recovered in Colombia.

Abstract Although the well-known work of Hipólito Villarroel, Enfermedades políticas que padece la capital de esta Nueva España (written at the end of the 18th Century) has been often cited and quoted, it has not yet deserved a real case study. The purpose of this paper is to contribute in this direction and examine some aspects of the Enfermedades from the perspective of the Enlightment, and the Bourbon Reforms, but above all, from that of the career and personal political experiences of the author in New Spain. This approach attests to the fact that even the most fervent supporters of the administrative modernization of Charles III were deeply influenced by the American realities which moderated or shifted their thought in a fashion not considered by the original Spanish models.

Resumen Aunque muy conocidas y citadas, las Enfermedades políticas que padece la capital de esta Nueva España, de Hipólito Villarroel, escritas a fines del siglo XVIII, no han sido, hasta hoy, objeto de un estudio monográfico completo. Es propósito del presente artículo aportar algo en esta línea y examinar algunas consideraciones de dicha obra a la luz del pensamiento ilustrado y del espíritu de las Reformas borbónicas, pero sobre todo, a la de la trayectoria vital y las experiencias políticas novohispanas de su propio autor. Dicho enfoque pone de manifiesto que incluso entre los más resueltos partidarios de la “modernización” administrativa carolina, el peso de las realidades americanas acabó por marcar improntas y adaptaciones particulares a los proyectos metropolitanos originales.

Abstract INTRODUCTION Cryptococcosis is the second most frequent cause of opportunistic infections in human immunodeficiency virus (HIV) patients in Colombia. We aimed to determine the prevalence of cryptococcosis in the Colombian department of Atlántico. METHODS An active search for cryptococcosis cases was conducted between 2015 and 2017 in health institutions by distributing surveys to clinicians and characterizing samples phenotypically and genotypically. RESULTS Thirty-eight cryptococcosis cases were identified (81.6% men, 76.3% HIV patients). The calculated annual prevalence was 5.08/1 million inhabitants. Cryptococcus neoformans var. grubii VNI was isolated in 34 cases. CONCLUSIONS These results provide the basis for passive surveillance of cryptococcosis.

ABSTRACT Cryptococcosis is a major invasive fungal disease related worldwide with the AIDS population. New reports of HIV/AIDS cases to the national public health surveillance system (SIVIGILA) in Colombia have shown that there is a growing community at risk of contracting cryptococcosis throughout the country who do not have access to ART. Even though the most prevalent species Cryptococcus neoformans is mainly associated with the HIV population, we report a fatal case of cryptococcosis in an AIDS patient in Barranquilla, associated with Cryptococcus gattii VGI, isolated from blood culture.

ABSTRACTINTRODUCTION:Cryptococcosis is an invasive disease acquired by inhalation of infectious propagules from the environment. Currently, compulsory notification of the spread of this disease is not required in Colombia. However, reporting of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome cases to the National Surveillance System has suggested that there is a growing population at risk of contracting cryptococcosis. Few studies have described the occurrence of cryptococcosis in Colombia. Therefore, in this study, we examined the pathology of this disease in Atlántico, Colombia and determined the distributions of Cryptococcus neoformans and Cryptococcus gattii in the environment.METHODS:Clinical samples/isolates were gathered from cases of cryptococcosis previously diagnosed at health institutions in Atlántico, and surveys were completed by clinicians. The environmental study considered 32 sampling points and three tree species, i.e., Quickstick ( Gliricidia sepium ), Almond ( Terminalia catappa ), and Pink trumpet ( Tabebuia rosea ). Environmental and clinical samples/isolates were analyzed for phenotypic and genotypic confirmation.RESULTS:From 1997-2014, 41 cases of cryptococcosis were reported. The mean patient age was 40.5 years (range: 18-63 years); 76% were men, and 78% were HIV positive. Isolation was possible in 38 cases ( C. neoformans , molecular type VNI in 37 cases and C. gattii , molecular type VGI in one case). In 2012-2014, 2,068 environmental samples were analyzed with a positivity of 0.4% ( C. neoformans , molecular type VNI) in Almond and Pink trumpet trees.CONCLUSIONS:Cryptococcus neoformans , molecular type VNI had a higher prevalence than C. gattii and was associated with human exposure and the pathogenesis of cryptococcosis in this geographical region.

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.

Objective Using the microscopic agglutination test (MAT) from 2010-2012 for identify ingleptospirosis-related and sociodemographic variables in patients havinga confirmed diagnosis of dengue and those for whom it had been discarded. Materials and Methods This was aretrospective study of 238 sera samples. 106 patients died, 64 of their samples were negative for dengue and 42 proved positive. 132 samples from live patients proved positive for dengue; 29 were confirmed by PCR and/orvirus isolation and 103 had positive IgM readings. MAT was used for all seraand diagnosing Leptospira, epidemiological records were reviewed and the data was analysed. Results 42 dengue positive patients died; 3 (7%) were positive for Leptospira interrogans sero group Australisautumnalis (two girls aged 5 and 17 years-old anda 14 year-old boy). Of the 64 deceased patients who proved negative for dengue, 7 (11%) were found positive for L.interrogans from sero groups Pomona, Autumnalis, Canicola and Ballum (5 malesaged 8to 58 years-old and 2 womenaged 35 and 56 years-old). Of the 103 living patients who proved positive for dengue IgM, 3 (2.9%) were positive for Leptospira icterohaemorrhagiae from the Cynopteri, Javanica Proechimys and Autumnalissero groups(1 maleand 2 females). None of the 29 living patients confirmedas having dengue were positive for Leptospira. Conclusions Leptospirosis should be suspected not onlyas the solecausative agent of febrile syndromebut also of co-infection which could compromisea patient and be related tomortality.

Objetivo Identificar la presencia de leptospirosis y las variables sociodemográficas relacionadas, en pacientes con diagnóstico confirmado y descartado de dengue en el periodo 2010-2012, por medio de la técnica de microaglutinación (MAT). Materiales y Métodos Se realizó un estudio descriptivo retrospectivo de 238 sueros: 106 de pacientes fallecidos: 64 dengue negativo y 42 dengue positivo y 132 muestras de pacientes vivos dengue positivo: 29 confirmados por PCR y/o aislamiento viral y 103 con IgM positiva, a todos los sueros se les realizó la técnica de MAT para Leptospira, se revisaron las fichas epidemiológicas y se analizaron los datos. Resultados De los 42 pacientes fallecidos dengue positivo, 3 (7%) se encontraron positivos para Leptospira interrogans serogrupo Australis y Autumnalis; 2 mujeres, de 5 y 17 años y un hombre de 14 años.De los 64 pacientes fallecidos negativos para dengue, 7(11%) se encontraron positivos para L. interrogans de los serogrupos Pomona, Autumnalis, Canicola y Ballum; 5 hombres; edades entre 8 y 58 años; y 2 mujeres edades de 35 y 56 años. De los 103 pacientes vivos con IgM positiva para dengue, 3(2,9%) se encontraron positivos para Leptospira de los serogrupos Icterohaemorrhagiae, Cynopteri, Javanica, Proechimys y Autumnalis; 1 hombre y 2 mujeres. En los 29 pacientes vivos confirmados para dengue, no se encontraron positivos para Leptospira. Conclusiones Se debe sospechar de leptospirosis, no solo como único agente causal del síndrome febril, sino también de la coinfección que podría comprometer al paciente y estar relacionada con la mortalidad.

Objetivo Identificar la presencia de leptospirosis y las variables sociodemográficas relacionadas, en pacientes con diagnóstico confirmado y descartado de dengue en el periodo 2010-2012, por medio de la técnica de microaglutinación (MAT). Materiales y Métodos Se realizó un estudio descriptivo retrospectivo de 238 sueros: 106 de pacientes fallecidos: 64 dengue negativo y 42 dengue positivo y 132 muestras de pacientes vivos dengue positivo: 29 confirmados por PCR y/o aislamiento viral y 103 con IgM positiva, a todos los sueros se les realizó la técnica de MAT para Leptospira, se revisaron las fichas epidemiológicas y se analizaron los datos. Resultados De los 42 pacientes fallecidos dengue positivo, 3 (7%) se encontraron positivos para Leptospira interrogans serogrupo Australis y Autumnalis; 2 mujeres, de 5 y 17 años y un hombre de 14 años.De los 64 pacientes fallecidos negativos para dengue, 7(11%) se encontraron positivos para L. interrogans de los serogrupos Pomona, Autumnalis, Canicola y Ballum; 5 hombres; edades entre 8 y 58 años; y 2 mujeres edades de 35 y 56 años. De los 103 pacientes vivos con IgM positiva para dengue, 3(2,9%) se encontraron positivos para Leptospira de los serogrupos Icterohaemorrhagiae, Cynopteri, Javanica, Proechimys y Autumnalis; 1 hombre y 2 mujeres. En los 29 pacientes vivos confirmados para dengue, no se encontraron positivos para Leptospira. Conclusiones Se debe sospechar de leptospirosis, no solo como único agente causal del síndrome febril, sino también de la coinfección que podría comprometer al paciente y estar relacionada con la mortalidad.

Objective Using the microscopic agglutination test (MAT) from 2010-2012 for identify ingleptospirosis-related and sociodemographic variables in patients havinga confirmed diagnosis of dengue and those for whom it had been discarded. Materials and Methods This was aretrospective study of 238 sera samples. 106 patients died, 64 of their samples were negative for dengue and 42 proved positive. 132 samples from live patients proved positive for dengue; 29 were confirmed by PCR and/orvirus isolation and 103 had positive IgM readings. MAT was used for all seraand diagnosing Leptospira, epidemiological records were reviewed and the data was analysed. Results 42 dengue positive patients died; 3 (7%) were positive for Leptospira interrogans sero group Australisautumnalis (two girls aged 5 and 17 years-old anda 14 year-old boy). Of the 64 deceased patients who proved negative for dengue, 7 (11%) were found positive for L.interrogans from sero groups Pomona, Autumnalis, Canicola and Ballum (5 malesaged 8to 58 years-old and 2 womenaged 35 and 56 years-old). Of the 103 living patients who proved positive for dengue IgM, 3 (2.9%) were positive for Leptospira icterohaemorrhagiae from the Cynopteri, Javanica Proechimys and Autumnalissero groups(1 maleand 2 females). None of the 29 living patients confirmedas having dengue were positive for Leptospira. Conclusions Leptospirosis should be suspected not onlyas the solecausative agent of febrile syndromebut also of co-infection which could compromisea patient and be related tomortality.

Introducción. Desde 1997 se viene realizando un programa nacional de vigilancia sobre la criptococosis en Colombia. Se presentan los resultados correspondientes a los pacientes diagnosticados entre el 2006 y el 2010. Objetivo. Analizar los datos obtenidos durante este periodo. Materiales y métodos. Análisis retrospectivo de las encuestas. Resultados. Durante los cinco años mencionados se recibieron 526 encuestas representativas del 72 % de la división política colombiana. La mayoría de pacientes (76,6 %) eran hombres y 74,9 % estaban entre los 21 y los 50 años. El factor de riesgo prevalente fue la infección por VIH (83,5 %), y la criptococosis definió el sida en 23 % de los casos. La incidencia anual promedio en la población general fue de 2,4 por un millón de habitantes mientras que, en pacientes con sida, aumentó a 3,3 por 1.000. En 474 encuestas se informaron manifestaciones clínicas; las más frecuentes fueron: cefalea (84,5 %), fiebre (63,4 %), náuseas y vómito (57,5 %), alteraciones mentales (46,3 %), signos meníngeos (33 %), tos (26,4 %) y alteraciones visuales (24,5 %). La neurocriptococosis se reportó en 81,8 % de los casos. El diagnóstico se hizo por examen directo, cultivo y antigenemia en 29,3 % de los casos. De 413 aislamientos recuperados, 95,6 % fueron C. neoformans var. grubii, 1 % C. neoformans var. neoformans, y 3,4 % C. gattii. En 71,6 % de los casos para el tratamiento se administró anfotericina B y en 28 % se combinó con fluconazol. Conclusiones. La vigilancia pasiva continúa siendo un marcador centinela para la infección por VIH, y constituye una aproximación sistemática al estudio de infecciones oportunistas en pacientes con sida, debido a que la criptococosis no es de notificación obligatoria en Colombia

Introduction: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. Objective: To analyze the data obtained during this period. Materials and methods: Retrospective analysis of the corresponding surveys. Results: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 106 inhabitants while in AIDS patients this rate rose to 3.3 x 103. In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. Conclusions: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia.

Introducción. En Cúcuta, Cryptococcus gattii de serotipo B se recupera comúnmente de pacientes inmunocompetentes con criptococosis, pero no ha sido recuperado del ambiente a pesar su alta incidencia, que es de 77 % de los casos reportados. Objetivo. El objetivo de este trabajo fue realizar un extenso muestreo ambiental en Cúcuta, para aislar C. gattii de serotipo B y expandir nuestro conocimiento sobre la ecología y la epidemiología de esta importante levadura. Materiales y métodos. Se recolectaron y se procesaron muestras asociadas con 3.634 árboles de 40 zonas de Cúcuta y 28 muestras cercanas a las casas de cuatro pacientes con criptococosis causada por C. gattii de serotipo B. El serotipo de los aislamientos recuperados se estableció usando PCR múltiple, el patrón molecular se determinó por RFLP del gen URA5 y la pareja sexual se determinó usando los iniciadores MfαU, MfαL, MFa2U y MFa2L. Resultados. Se procesaron 4.389 muestras y se recuperó un aislamiento de C. gattii de serotipo B (VGI/a), dos aislamientos de C. gattii de serotipo C (VGIII/α) y tres aislamientos de C. neoformans var. grubii de serotipo A (VNI/α). La densidad de los aislamientos recuperados varió entre 50 y 350 UFC/g de suelo. Conclusiones. Éste es el primer reporte de la recuperación ambiental de C. gattii de serotipo B en Cúcuta. Sin embargo, por la baja tasa de recuperación de aislamientos únicamente en suelo, el nicho ambiental de C. gattii no se pudo establecer, por lo que es necesario realizar posteriores estudios ambientales en Cúcuta, debido a que este serotipo, no sólo está causando criptococosis, sino también muestra una gran virulencia después del brote ocurrido en Vancouver.

Introduction. In Cúcuta, Cryptococcus gattii serotype B is commonly recovered from immunocompetent patients with cryptococcosis, but it has not been recovered from the environment in spite of its high incidence which is 77% out of reported cases. Objective. The aim of this work was to carry out an extensive environmental sampling in Cúcuta, in an attempt to isolate C. gattii serotype B and to expand our knowledge about the ecology and epidemiology of this important yeast. Materials and methods. Samples associated with 3,634 trees from 40 zones of Cúcuta were collected and processed with 28 samples collected near the houses of four patients with cryptococcosis caused by C. gattii serotype B. The serotype of the recovered isolates was done using multiplex PCR, molecular patterns were determined by RFLP of the URA5 gene and mating type was determined using the primers MfαU, MfαL, MFa2U and MFa2L. Results. In total, 4,389 samples were processed and one isolate of C. gattii serotype B (VGI/a), two isolates of C. gattii serotype C (VGIII/α) and three isolates of C. neoformans var. grubii, serotype A (VNI/α), were recovered. The density of the recovered isolates varied from 50 to 350 cfu/g of soil. Conclusions. This is the first report on the environmental isolation of C. gattii serotype B from Cúcuta. However, because of the low rate of recovery of isolates from soil only, the environmental niche of C. gattii has not been established and further environmental studies in Cúcuta are necessary, owing that this serotype is not only causing cryptococcosis but also has shown a higher virulence after the Vancouver outbreak.

La tipificación molecular de los aislamientos del complejo C. neoformans/C. gattii constituye hoy en día una nueva herramienta para la vigilancia de este importante patógeno oportunista. Por medio de esta comunicación queremos dar a conocer al cuerpo médico y de laboratorio en Colombia, la importancia de la PCR huella digital en el estudio de la diversidad genética de los aislamientos del complejo C. neoformans/C. gattii obtenidos en el país. Adicionalmente, los resultados obtenidos a partir de la tipificación molecular nos permiten complementar la información recolectada en la encuesta nacional sobre la criptococosis liderada por el Grupo de Microbiología del Instituto Nacional de Salud. Los aislamientos del complejo se pueden clasificar en ocho patrones moleculares de acuerdo con la técnica de PCR huella digital con iniciadores universales, que permite agrupar a los miembros del complejo según su especie, en el caso de C. neoformans, de acuerdo con su variedad. Realizar la vigilancia molecular de los aislamientos del complejo C. neoformans/C. gattii es una herramienta epidemiológica de gran valor, teniendo en cuenta que la criptococosis ha adquirido en los últimos años un gran interés debido al creciente número de pacientes inmunosuprimidos.

The molecular typing of the Cryptococcus neoformans/Cryptococcus gattii species complex is an useful tool for the molecular surveillance of this important opportunistic pathogen. The aim of this short communication is to inform physicians and laboratory personnel in Colombia about the importance of PCR fingerprinting in the comprehensive study of the genetic diversity of the C. neoformans/C. gattii species complex in the country. Furthermore, the results obtained from this molecular typing will enable us t complement the information gathered during the National Survey about cryptococcosis lead by the Microbiology Group of the Instituto Nacional de Salud. Isolates of the complex can be classified in 8 molecular patterns according to PCR fingerprinting using universal primers, which allows grouping the members of the complex according to species and, for C. neoformans, according to variety. The molecular surveillance of the C. neoformans/ C. gattii species complex isolates has become an epidemiological tool of great value since cryptococcosis has gained an important relevance in recent years due to the increasing number of immune-suppressed patients.