Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans.

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

Pediatric Cryptococcosis.

BACKGROUND: Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency virus (HIV), but reported pediatric disease prevalence is much lower than in adults. METHODS: PubMed and Ovid Global Health databases were searched with the terms "cryptococcosis," "cryptococcal meningitis," " Cryptococcus neoformans " or " Cryptococcus gattii ." All studies reporting pediatric specific data in the English language from 1980 up until December 2022 were included. RESULTS: One hundred sixty-eight publications were reviewed totaling 1469 children, with the majority reported from Africa (54.2%). Sixty-five percent (961) were HIV positive, 10% (147) were non-HIV immunocompromised and 19% (281) were immunocompetent. Clinical signs and symptoms were only reported for 458 children, with fever (64%), headache (55%) and vomiting (39%) being the most common. Most children (80%) suffered from meningoencephalitis. Lung involvement was rarely described in HIV-positive children (1%), but significantly more common in the non-HIV immunocompromised (36%) and immunocompetent (40%) groups ( P < 0.0001). Only 22% received the recommended antifungal combination therapy, which was significantly higher in immunocompetent children than those with HIV (39% vs. 6.8%; P < 0.0001). Overall mortality was 23%. A significant higher mortality was observed in children with HIV compared with immunocompetent children (32% vs. 16%; P < 0.001), but not compared with children with non-HIV immunosuppression (25). CONCLUSIONS: This is the largest review of pediatric cryptococcosis with new observations on differences in clinical presentation and outcome depending on the underlying condition. The lack of granular clinical data urges prospective clinical epidemiological studies for improved insight in the epidemiology, management and outcome of cryptococcosis in children.

Cryptococcus neoformans- and Cryptococcus gattii-specific IgG, IgA and IgM differ among children and adults with and without cryptococcosis from Colombia.

Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg) cause cryptococcosis, a life-threatening systemic mycosis of global distribution affecting mainly immunocompromised adults. Although a humoral response occurs during cryptococcosis, the role of antibody production against this mycosis is not fully understood. We aimed to determine total and specific antibodies against cryptococcal protein antigens in sera from people with and without a diagnosis of cryptococcosis from Colombia. Using ELISA, total and specific levels of immunoglobulin (Ig)G, IgA and IgM were determined in sera from children and adults with (n = 109) and without (n = 119) cryptococcosis. Specific antibodies were those binding Cn- and Cg-protein antigens. In general, the mean of the total IgG production was higher in cryptococcosis patients than in controls (13 942.32 vs. 6459.91 µg/ml), while levels of IgA (488.13 vs. 1564.53 µg/ml) and IgM (775.69 vs. 1014.72 µg/ml) were higher in controls than in cryptococcosis patients (P ≤ .05). In patients with cryptococcosis, total IgG, IgA and IgM levels were higher in HIV + compared with HIV- (P ≤ .05). Specific antibodies tended to be higher in cryptococcosis patients than in controls and in adults than in children, with a positive correlation between antibody reactivity and age. All immunoglobulins were more reactive against Cn-proteins than Cg-proteins. Overall, a positive weak correlation between total and specific antibodies was found, although not always statistically significant. In patients with cryptococcosis from Colombia, the levels of immunoglobulins, total and specific, differ with respect to people without cryptococcosis. Variations in antibody production among adults and children with cryptococcosis and between Cn- and Cg-protein antigens were as well established. Our findings encourage further studies to determine the role of humoral immunity for host defense against cryptococcosis.

Differential IgG, IgA, and IgM production and their reactivity with cryptococcal proteins, both among children and adults with and without a diagnosis of cryptococcosis from Colombia, lead to reappraise the study of the potential role of antibody production as host defense against this fungal infection.

Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics.

Purpose of Review: Cryptococcosis of the central nervous system due to Cryptococcus gattii species complex is a serious mycosis with worldwide distribution but of great importance in the tropics. This article aims to review the progress made in these regions in the knowledge of this disease and its etiological agent. Recent Findings: They can be summarized in the presence in apparently immunocompetent patients of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a hidden risk factor for acquiring C. gattii infection; this finding strengthens the concept that C. gattii is an opportunistic pathogen. A greater knowledge of the clinical and molecular epidemiology of C. gattii infection and of the different environmental niches of this fungus in the tropics. The discovery of a new lineage of C. gattii, VGV, in environmental samples from Africa. Until now, the COVID-19 pandemic has not meant an increase in cryptococcosis cases. Summary: Advances have been made in the identification of risk factors for cryptococcosis due to C. gattii as well as in the knowledge of its etiological agent and its relationship with the environment. Remarkably, there have been no significant achievements in diagnosis and treatment notwithstanding the documented importance.

Fatal brain hemorrhage after Bothrops asper bite in the Catatumbo region of Colombia / [Hemorragia cerebral fatal después de una mordedura de serpiente Bothrops asper en la región del Catatumbo, Colombia].

Snake bites are a public health problem in tropical and subtropical regions of the world. They occur especially in rural workers and are an important source of disability and mortality. We present the case of a 59-year-old farmer from the Catatumbo region of Colombia who was bitten by a B. asper snake and suffered a fatal brain hemorrhage after the event. We draw attention to the severe bleeding disorder in contrast with the slight changes at the site of the bite, as well as on the importance of the early treatment of poisoning with antivenom even in the absence of significant skin manifestations.

Las mordeduras de serpientes son un problema de salud pública en regiones tropicales y subtropicales del mundo. Ocurren, especialmente, en trabajadores rurales, y son una importante fuente de discapacidad y mortalidad. Se presenta el caso de un hombre de 59 años, agricultor de la región del Catatumbo (Colombia), quien sufrió la mordedura de una serpiente Bothrops asper, la cual le produjo una hemorragia cerebral fatal. Se llama la atención sobre el grave trastorno hemorrágico en contraste con los leves cambios en el sitio de la mordedura, así como sobre la necesidad del tratamiento temprano de la intoxicación con el suero antiofídico, incluso, en ausencia de manifestaciones cutáneas significativas.

Hemorragia cerebral fatal después de una mordedura de serpiente Bothrops asper en la región del Catatumbo, Colombia / Fatal brain hemorrhage after Bothrops asper bite in the Catatumbo region of Colombia

Resumen: Las mordeduras de serpientes son un problema de salud pública en regiones tropicales y subtropicales del mundo. Ocurren, especialmente, en trabajadores rurales, y son una importante fuente de discapacidad y mortalidad. Se presenta el caso de un hombre de 59 años, agricultor de la región del Catatumbo (Colombia), quien sufrió la mordedura de una serpiente Bothrops asper, la cual le produjo una hemorragia cerebral fatal. Se llama la atención sobre el grave trastorno hemorrágico en contraste con los leves cambios en el sitio de la mordedura, así como sobre la necesidad del tratamiento temprano de la intoxicación con el suero antiofídico, incluso, en ausencia de manifestaciones cutáneas significativas.

Abstract: Snake bites are a public health problem in tropical and subtropical regions of the world. They occur especially in rural workers and are an important source of disability and mortality. We present the case of a 59-year-old farmer from the Catatumbo region of Colombia who was bitten by a B. asper snake and suffered a fatal brain hemorrhage after the event. We draw attention to the severe bleeding disorder in contrast with the slight changes at the site of the bite, as well as on the importance of the early treatment of poisoning with antivenom even in the absence of significant skin manifestations.

Cryptococcosis in Hematopoietic Stem Cell Transplant Recipients: A Rare Presentation Warranting Recognition.

Cryptococcosis, a life-threatening mycosis caused mainly by Cryptococcus neoformans, appears to be distinctly rare in hematopoietic stem cell transplant (HSCT) recipients. When it occurs, this fungal infection is a major limitation for a successful transplant. This review comprehensively analyses 24 cases, reported in the literature, of patients with haematological malignancies including leukemias, multiple myeloma, and lymphomas, as indication for HSCT, who presented with cryptococcosis after transplantation. Of the 24 cases, 11 each occurred in patients receiving allogeneic and autologous stem cell transplants, from bone marrow, peripheral blood, and umbilical cord blood. HSCT recipients were slightly more often male, and the age of the patients ranged from 12 to 74 years. Antifungal prophylaxis was reported in most cases. Clinical manifestations of cryptococcal disease included more frequently central nervous system involvement followed by fungaemia, disseminated infection, pulmonary cryptococcosis, cerebellitis, and diarrhea. Diagnosis differed depending on the clinical presentation but habitually included cryptococcal antigen assay, India ink, and culture. Notably, not only C. neoformans but also C. albidus, C. terreus, C. laurentii, and C. adeliensis were identified as the causal species, the last two including strains resistant to fluconazole. Amphotericin B, alone or in combination, was the most common antifungal drug used for the treatment of cryptococcosis in HSCT recipients. Due to the small number of cases, it was not possible to establish if mortality rate, which was the same as survival rate, depends on the effect of the immunosuppressive regimen, the site of cryptococcal infection, and/or the antifungal therapy used to control the mycosis. Although uncommon, the recognition of cryptococcal disease in stem cell transplant is essential for a timely and adequate treatment, improved prognosis, reduced morbidity and mortality, and successful transplantation.

Un caso de melanosis neurocutánea: el lado oscuro del nevus melanocítico congénito gigante / A case of neurocutaneous melanosis: the dark side of the giant congenital melanocytic nevus

RESUMEN La melanosis neurocutánea es una facomatosis, no hereditaria, caracterizada por la proliferación de melanocitos y de depósitos de melanina en el sistema nervioso central, asociada a un nevus melanocítico congénito gigante o a múltiples nevus melanocíticos satélites. CASO CLÍNICO. Una mujer joven con nevus melanocítico congénito gigante y satelitosis, presentó hipertensión intracraneana asociada a hidrocefalia comunicante. Se le practicó derivación del líquido cefalorraquídeo con mejoría parcial, luego presentó convulsiones y afectación medular cervical que la llevó a la ventilación mecánica prolongada y finalmente a la muerte. La resonancia magnética evidenció lesiones en las leptomeninges. CONCLUSIONES. La melanosis neurocutánea debe considerarse en pacientes adultos con nevus melanocítico congénito que presenten manifestaciones clínicas neurológicas.

SUMMARY Neurocutaneous melanosis is a non-hereditary phakomatosis, characterized by the proliferation of melanocytes and melanin deposits in the central nervous system associated with a giant congenital melanocytic nevus or multiple melanocytic nevi satellites. CLINICAL CASE. A young woman with congenital giant melanocytic nevus and satelitosis, presented with intracraneal hypertension associated with communicating hydrocephalus. She was treated with cerebrospinal fluid shunt with partial improvement; but she worsened, presenting seizures and later cervical spinal cord involvement that led to prolonged mechanical ventilation and eventually death. MRI showed lesions in leptomeninges. CONCLUSIONS. Neurocutaneous melanosis should be considered in adult patients with congenital melanocytic nevus and clinical neurological manifestations.

Amnesia anterógrada debida a lesión bilateral de los hipocampos en un paciente probablemente intoxicado con metanol / Anterograde amnesia due to bilateral lesion of the hippocampus in a patient probably intoxicated with metanol

RESUMEN Se presenta el caso clínico de un hombre de 56 años que ingresó con un cuadro agudo de alteración de la conciencia luego de intoxicación alcohólica. Durante su hospitalización se evidenció alteración de la memoria anterógrada y neuropatía óptica derecha. Las imágenes diagnósticas demostraron lesiones bilaterales de los hipocampos, globos pálidos y corteza cerebral frontal paramediana. La evaluación neuropsicológica confirmó una grave amnesia anterógrada que mejoró muy poco al cabo de 2 años de seguimiento. A pesar de la falta de confirmación por el laboratorio, las manifestaciones clínicas y las imágenes están a favor de una intoxicación por metanol. Se llama la atención sobre esta rara presentación clínica.

SUMMARY We report the case of a 56-year-old man who was hospitalized because acute altered consciousness after alcoholic intoxication. During his hospitalization, there was observed an alteration of anterograde memory and right optic neuropathy. Diagnostic images showed bilateral lesions of the hippocampus, globus pallidus and paramedian cerebral frontal cortex. The neuropsychological evaluation confirmed a severe anterograde amnesia that barely improved after 2 years of follow up. Despite the lack of confirmation by the laboratory, the clinical manifestations and imaging results are in favor of methanol intoxication. Attention is drawn to this rare clinical presentation.

The status of cryptococcosis in Latin America.

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.

Cryptococcosis in Colombia: Compilation and Analysis of Data from Laboratory-Based Surveillance.

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.

Guillain-Barré Syndrome Associated with Zika Virus Infection in Colombia.

BACKGROUND: Zika virus (ZIKV) infection has been linked to the Guillain-Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain-Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain-Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection. METHODS: A total of 68 patients with the Guillain-Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays. RESULTS: A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain-Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain-Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain-Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain-Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain-Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain-Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR. CONCLUSIONS: 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.).

Intracerebral hemorrhage caused by varicella-induced thrombocytopenia.

We present the case of a previously healthy 44-years-old man with chickenpox, severe thrombocytopenia, mucosal hemorrhage, and intracerebral hemorrhage in the right hemisphere. The patient was treated with platelets and high doses of steroids. He recovered although with persistent left homonymous hemianopsia and epilepsy, which were controlled with medication.

Hemorragia cerebral secundaria a trombocitopenia por varicela / Intracerebral hemorrhage caused by varicella-induced thrombocytopenia

Se presenta el caso de un hombre de 44 años, previamente sano, con varicela, trombocitopenia grave, manifestaciones hemorrágicas en mucosas y una extensa hemorragia cerebral en el hemisferio derecho. Su tratamiento incluyó la transfusión de plaquetas y altas dosis de esteroides. El paciente mejoró, aunque persistieron la hemianopsia homónima izquierda y la epilepsia, tratada con medicación.

We present the case of a previously healthy 44-years-old man with chickenpox, severe thrombocytopenia, mucosal hemorrhage, and intracerebral hemorrhage in the right hemisphere. The patient was treated with platelets and high doses of steroids. He recovered although with persistent left homonymous hemianopsia and epilepsy, which were controlled with medication.

Nocardiosis diseminada en una paciente VIH negativa. A propósito deun caso de difícil tratamiento / Diseminated nocardiosis in a HIV-negative patient. A difficult to treat case

(AU)La nocardiosis diseminada es una enfermedad grave, especialmente cuando hay afectación del sistema nerviosocentral. Se presenta el caso de una mujer adulta, VIH negativa, que presentó nocardiosis diseminada conafectación pulmonar, muscular, articular, encefálica y ocular. Nocardia spp. fue cultivada a partir de biopsiade masa pulmonar. El manejo fue difícil debido a la falta de respuesta al tratamiento antibiótico tradicionalcon trimetropín-sulfametoxazol, amikacina, ceftriaxona y meropenem. Finalmente, mejoró con el tratamientoconjugado de linezolid, claritromicina y moxifloxacino durante varios meses. Se discuten aspectos relacionadoscon el tratamiento de esta enfermedad

Management of Cryptococcus gattii meningoencephalitis.

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.

Retrospective study of the epidemiology and clinical manifestations of Cryptococcus gattii infections in Colombia from 1997-2011.

BACKGROUND: Cryptococcosis 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 FINDINGS: From 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/SIGNIFICANCE: The 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 in Colombian children and literature review.

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.