The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).

Cryptococcosis is a fungal disease caused by Cryptococcus neoformans and Cryptococcus gattii. By inhalation and subsequent pulmonary infection, it may disseminate to the CNS and cause meningitis or meningoencephalitis. Most cases occur in immunosuppressed hosts, including patients with HIV/AIDS, patients receiving immunosuppressing drugs, and solid organ transplant recipients. However, cryptococcosis also occurs in individuals with apparently healthy immune systems. A growing number of cases are caused by C. gattii, with infections occurring in both immunosuppressed and immunocompetent individuals. In the majority of documented cases, treatment of C. gattii infection of the CNS requires aggressive management of raised intracranial pressure along with standard antifungal therapy. Early cerebrospinal fluid evacuation is often needed through placement of a percutaneous lumbar drain or ventriculostomy. Furthermore, pharmacological immunosuppression with a high dose of dexamethasone is sometimes needed to ameliorate a persistently increased inflammatory response and to reduce intracranial pressure. In this Grand Round, we present the case of an otherwise healthy adolescent female patient, who, despite aggressive management, succumbed to C. gattii meningoencephalitis. We also present a review of the existing literature and discuss optimum clinical management of meningoencephalitis caused by C. gattii.

Cryptococcosis is a life-threatening fungal infection caused by the encapsulated yeasts Cryptococcus neoformans and C. gattii, acquired from the environment. In Latin America, as occurring worldwide, C. neoformans causes more than 90% of the cases of cryptococcosis, affecting predominantly patients with HIV, while C. gattii generally affects otherwise healthy individuals. In this region, cryptococcal meningitis is the most common presentation, with amphotericin B and fluconazole being the antifungal drugs of choice. Avian droppings are the predominant environmental reservoir of C. neoformans, while C. gattii is associated with several arboreal species. Importantly, C. gattii has a high prevalence in Latin America and has been proposed to be the likely origin of some C. gattii populations in North America. Thus, in the recent years, significant progress has been made with the study of the basic biology and laboratory identification of cryptococcal strains, in understanding their ecology, population genetics, host-pathogen interactions, and the clinical epidemiology of this important mycosis in Latin America.

BackgroundCryptococcosis due to Cryptococcus gattii is endemic in various parts of the world, affecting mostly immunocompetent patients. A national surveillance study of cryptococcosis, including demographical, clinical and microbiological data, has been ongoing since 1997 in Colombia, to provide insights into the epidemiology of this mycosis.Methodology/Principal FindingsFrom 1,209 surveys analyzed between 1997–2011, 45 cases caused by C. gattii were reported (prevalence 3.7%; annual incidence 0.07 cases/million inhabitants/year). Norte de Santander had the highest incidence (0.81 cases/million/year), representing 33.3% of all cases. The male: female ratio was 3.3∶1. Mean age at diagnosis was 41±16 years. No specific risk factors were identified in 91.1% of patients. HIV infection was reported in 6.7% of patients, autoimmune disease and steroids use in 2.2%. Clinical features included headache (80.5%), nausea/vomiting (56.1%) and neurological derangements (48.8%). Chest radiographs were taken in 21 (46.7%) cases, with abnormal findings in 7 (33.3%). Cranial CT scans were obtained in 15 (33.3%) cases, with abnormalities detected in 10 (66.7%). Treatment was well documented in 30 cases, with most receiving amphotericin B. Direct sample examination was positive in 97.7% cases. Antigen detection was positive for all CSF specimens and for 75% of serum samples. C. gattii was recovered from CSF (93.3%) and respiratory specimens (6.6%). Serotype was determined in 42 isolates; 36 isolates were serotype B (85.7%), while 6 were C (14.3%). The breakdowns of molecular types were VGII (55.6%), VGIII (31.1%) and VGI (13.3%). Among 44 strains, 16 MLST sequence types (ST) were identified, 11 of them newly reported.Conclusions/SignificanceThe results of this passive surveillance study demonstrate that cryptococcosis caused by C. gattii has a low prevalence in Colombia, with the exception of Norte de Santander. The predominance of molecular type VGII is of concern considering its association with high virulence and the potential to evolve into outbreaks.

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.

Introducción. Con el fin de conocer la situación de la criptococosis en Colombia se ha llevado a cabo una encuesta nacional. El presente estudio analiza la información recogida de 1997 a 2005. Materiales y métodos. Se utilizó el formato de encuesta de la Confederación Europea de Micología Médica. Resultados. Se recibieron 931 encuestas de 76 centros. Se identificaron 891 (95,7%) casos de neurocriptococosis, 27 (2,9%) de formas pulmonares, cinco (0,5%) de lesiones cutáneas, dos (0,2%) de ganglionares, dos (0,2%) de úlceras orofaríngeas y un caso (0,1%) de cada una de las siguientes formas clínicas: peritonitis, lesión hepática, celulitis de los miembros inferiores e infección de las vías urinarias. El 82,7% fueron hombres con predominio de los adultos jóvenes. Sin embargo, se reportaron 25 (2,7%) niños. La infección por el virus de la inmunodeficiencia humana se encontró en el 78,1% de los casos. La incidencia promedio anual de criptococosis en la población general fue de 2,4 casos x10 6 , pero en los pacientes con sida se elevó a 3,0 casos x 10 3 . Las manifestaciones clínicas más frecuentes fueron: cefalea (85,2%), náuseas y vómito (59,1%), fiebre (59%), cambios mentales (46,2%) y signos meníngeos (33,4%). El examen directo de líquido cefalorraquídeo fue positivo en el 92,8% de los casos y el hongo se recuperó en el 90,3%. El antígeno capsular tuvo una positividad del 98,9% en el líquido cefalorraquídeo y del 93,7% en el suero. De 788 aislamientos remitidos, 95,9% fueron Cryptococcus neoformans var. grubii serotipo A, 0,3%, var. neoformans serotipo D, 3,3%, C. gattii serotipo B y 0,5%, C. gattii serotipo C. La mayoría de los pacientes fueron tratados inicialmente con anfotericina B. Conclusión: La criptococosis es una enfermedad cuya incidencia aumentó con la pandemia del VIH y constituye un marcador centinela de sida en Colombia.

The passive and voluntary surveillance of cryptococcosis in Colombia since 1997 has seen an increasing participating rate, revealing its importance to both in immunosuppressed and immunocompetent people. The present work details the national data gathered in 1997–2016, through a retrospective analysis of the information collected in the survey. From a total of 1974 cases reported, an overall incidence of 0.23 cases per 100,000 people was found. This incidence rose to 1.1 cases per 1000 people in the Acquired Immunodeficiency Syndrome (AIDS) population. Cryptococcosis was most common in male young adults (26–40 years), with a male:female ratio of 3.9:1 in the general population and 5.4:1 in Human Immunodeficiency Virus (HIV) patients. Culture was the most common form of diagnosis in 96.3% of cases, recovering C. neoformans species in 87.5% and C. gattii in 3.1% of samples. VNI was the most prevalent (96.1%) molecular type, while VGII predominated in C. gattii isolates (54.3%). Early mortality was reported as the outcome in 47.5% of patients. Cryptococcosis remains an important opportunistic disease in Colombia and is gaining status as a primary pathogen in apparently immunocompetent patients. Our findings show the importance of including cryptococcosis as a notifiable disease, which will allow for improving opportune diagnosis and treatment, resulting in better patient outcomes.

A previous study carried out in a tertiary care hospital in Colombia demonstrated the usefulness of the Cryptococcus capsular antigen detection by latex (CrAg Latex) in the early diagnosis of cryptococcosis in HIV-infected patients with low CD4 + levels. The aim of this study was to establish the performance of a new rapid lateral flow assay (CrAg LFA) in preserved sera of those HIV-infected patients collected between 2001 and 2006. A total of 421 sera from 297 patients with a confirmed diagnosis of HIV were tested with CrAg LFA and results compared with those obtained with CrAg Latex. All patients provided informed consent for specimen collection. A concordance of 100% was found between positive results obtained by both methods. However, 13 sera that were negative by CrAg Latex, were positive by CrAg LFA (3.1%). In these positive patients, median of CD4 + levels was 67 cells/μl (8-608 cells/μl), while median of viral load was 118,965 copies/ml (50-500,000 copies/ml). Patients who were negative for cryptococcosis had a median of 177 cells/μl in CD4 + levels (4-2516 cells/μl) and a median of 62,318 copies/ml in viral loads (25-50,000 copies/ml). A significant statistical difference was found when comparing CD4 + levels and viral load in patients positive for cryptococcosis and those that were proven to be negative (P < 0.0001). The use of Point-of-Care Tests (POCT) like CrAg LFA play an important role in the diagnosis of infectious diseases, especially in resource limited settings, where it will be a useful means to diagnose cryptococcosis early in HIV patients.