Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

Arsenic distribution in a pasture area impacted by past mining activities.

Former mine exploitations entail a serious threat to surrounding ecosystems as after closure of mining activities their unmanaged wastes can be a continuous source of toxic trace elements. Quite often these mine sites are found within agricultural farming areas, involving serious hazards as regards product (feed/food) quality. In this work a grazing land impacted by the abandoned mine exploitation of an arsenical deposit was studied so as to evaluate the fate of arsenic (As) and other trace elements and the potential risks involved. With this aim, profile soil samples (0-50cm) and pasture plant species (Agrostis truncatula, Holcus annus and Leontodon longirostris) were collected at different distances (0-100m) from the mine waste dump and analyzed for their trace element content and distribution. Likewise, plant trace element accumulation from impacted grazing soils and plant trace element translocation were assessed. The exposure of livestock grazing animals to As was also evaluated, establishing its acceptability regarding food safety and animal health. International soil guideline values for As in grazing land soils (50mgkg-1) resulted greatly exceeded (up to about 20-fold) in the studied mining-affected soils. Moreover, As showed a high mobilization potential under circumstances such as phosphate application or establishment of reducing conditions. Arsenic exhibited relatively high translocation factor (TF) values (up to 0.32-0.89) in pasture plant species, reaching unsafe concentrations in their above-ground tissues (up to 32.9, 16.9 and 9.0mgkg-1 in Agrostis truncatula, Leontodon longirostris and Holcus annus, respectively). Such concentrations represent an elevated risk of As transfer to the high trophic-chain levels as established by international legislation. The limited fraction of arsenite found in plant roots should play an important role in the relatively high As root-to-shoot translocation shown by these plant species. Both soil ingestion and pasture intake resulted important entrance pathways of As into livestock animals, showing quite close contribution levels. The cow acceptable daily intake (ADI) of As regarding food safety was surpassed in some locations of the study area when the species Agrostis truncatula was considered as the only pasture feed. Restrictions in the grazing use of lands with considerable As contents where this plant was the predominant pasture species should be established in order to preserve food quality. Therefore, the exposure of livestock animals to As via both soil ingestion and pasture consumption should be taken into account to establish the suitability of mining-impacted areas for gazing.

Comparative Study on the Efficiency of Mercury Removal From Wastewater Using Bacterial Cellulose Membranes and Their Oxidized Analogue.

A comparative study was conducted on the efficiency of mercury removal using bacterial nanocellulose (BNC) membranes obtained from the fermentation of the microorganism Komagataeibacter medellinensis, in contrast with its oxidized analog obtained by modifying the bacterial nanocellulose membranes via oxidation with 2,2,6,6-Tetramethylpiperidine-1-oxyl. Both types of membranes (modified and unmodified) were characterized to identify variations in the Physico-chemical parameters after modification. FTIR spectra confirmed the chemical modification of cellulose in all reaction conditions by the presence of a new characteristic band at ∼1730 cm-1, corresponding to the new carboxylic groups produced by the oxidative process, and the decline of the band at ∼1,650 cm-1, corresponding to the hydroxyl groups of the C6 carbon. While the XRD profiles indicated that the percentage of BNC crystallinity decreased and the SEM images showed that the nanoribbon network was interrupted as the amount of oxidizing agent increased. The kinetics of mercury removal from both types of membrane was evaluated by calculating the concentration of mercury at different times and establishing a mathematical model to describe the kinetics of this process. The modified membranes improved significantly the adsorption process of the metal ion and it was found that the modification that results in the greatest adsorption efficiency was BNC-m 7.5 with a value of 92.97%. The results obtained suggest that the modification of the bacterial nanocellulose membranes by oxidation transcendentally improves the mercury removal capacity, outlining the modified membranes as an excellent material for mercury removal in wastewater.

Distribution and mobility of mercury in soils of a gold mining region, Cuyuni river basin, Venezuela.

An extensive and remote gold mining region located in the East of Venezuela has been studied with the aim of assessing the distribution and mobility of mercury in soil and the level of Hg pollution at artisanal gold mining sites. To do so, soils and pond sediments were sampled at sites not subject to anthropological influence, as well as in areas affected by gold mining activities. Total Hg in regionally distributed soils ranged between 0.02 mg kg(-1) and 0.40 mg kg(-1), with a median value of 0.11 mg kg(-1), which is slightly higher than soil Hg worldwide, possibly indicating long-term atmospheric input or more recent local atmospheric input, in addition to minor lithogenic sources. A reference Hg concentration of 0.33 mg kg(-1) is proposed for the detection of mining affected soils in this region. Critical total Hg concentrations were found in the surrounding soils of pollutant sources, such as milling-amalgamation sites, where soil Hg contents ranged from 0.16 mg kg(-1) to 542 mg kg(-1) with an average of 26.89 mg kg(-1), which also showed high levels of elemental Hg, but quite low soluble+exchangeable Hg fraction (0.02-4.90 mg kg(-1)), suggesting low Hg soil mobility and bioavailability, as confirmed by soil column leaching tests. The vertical distribution of Hg through the soil profiles, as well as variations in soil Hg contents with distance from the pollution source, and Hg in pond mining sediments were also analysed.

Effect of ultra-fine friction grinding on the physical and chemical properties of curcuma (Curcuma longa L.) suspensions.

Curcuma longa is a rhizome used for the extraction of curcumin, a yellow colorant that only represents 3 wt% of the dried rhizome. To increase the possibility of using the entire rhizome as a food colorant, in the present investigation, the effect of ultra-fine friction grinding (supermasscolloider) to obtain turmeric suspensions was evaluated. To achieve this goal, two distances between the grinding stones or Gap were evaluated (G of -1 and -1.5), and the obtained suspensions were characterized by infrared spectroscopy and through the determination of curcumin content, color, particle size, sedimentation index, serum cloudiness, and microstructure. The results establish that a lower G contributes to an increase in the release of curcumin in the suspension up to 21%, which is related to a greater tendency for yellow coloration, observed in the increase of the * b coordinate of color (from 61.588 to 66.497). Additionally, it was found that a lower G generates smaller particle sizes, which is related to a lower turbidity. PRACTICAL APPLICATION: This research shows that ultra-fine friction grinding (UFFG) has great potential for the development of turmeric suspensions. The results have applications in the food industry sector, because UFFG could be used to produce different types of vegetable suspensions.

Gestational diabetes mellitus in a cohort of HIV-1 infected women.

OBJECTIVES: We undertook a prospective study to estimate the prevalence of gestational diabetes mellitus (GDM) and associated risk factors in a cohort of 669 HIV-1 infected women. METHODS: The O'Sullivan and glucose tolerance tests were performed during regular visits of 609 mothers. RESULTS: The median age of the cohort was 30.7 years (range 16-44), with most women having had heterosexual contact (67%). The majority were in Centers for Disease Control (CDC) category A (71%) and 53% exhibited hepatitis C co-infection. Median viral load and CD4 count at third trimester were 545 cells/microL (range 139-1690 cells/microL) and 1.9 log (range 1.7-5.4), respectively. Seventy-four per cent of the patients were treated with highly active antiretroviral therapy (HAART), of whom 41% received a protease inhibitor (PI). An above-average prevalence of 7% [95% confidence interval (CI) 5.2-9.5] for positive GDM diagnosis was found. Risk factors associated with GDM in univariate analysis included older age, hepatitis C co-infection, stavudine and PI exposure. However, only older age [adjusted odds ratio (AOR) 1.09, 95% CI 1-1.1] and PI exposure (AOR 2.4, 95% CI 1-5.3) remained as independent risk factors for GDM development in multivariate analysis. CONCLUSIONS: In our cohort, the prevalence of GDM appears to be increased, with older age and PI exposure contributing as significant independent risk factors.

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study.

SETTING: Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. OBJECTIVE: To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. DESIGN: Observational study of TB diagnosed in HIV-infected children in 2011-2013. RESULTS: Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes. CONCLUSION: Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.

[Effectiveness of antiretroviral therapy in HIV-1 infected children. A cross-sectional study]. / Efectividad de la terapia antirretroviral en niños con infección por VIH-1. Corte transversal.

INTRODUCTION: There are few cross-sectional studies describing the current situation of HIV-1-infected children. Such studies would be useful to determine patients' clinical and immunologic and virologic status, currently prescribed therapies and their associated toxicity. OBJECTIVES: To perform a descriptive analysis of the clinical, immunological and virological status of HIV-1-infected children followed-up in the pediatric unit of a tertiary hospital and describe the current antiretroviral therapies used to treat them. MATERIAL AND METHODS: A cross-sectional study was performed. Data were collected from all HIV-1-infected children followed-up until January 2002 in a large pediatric referral hospital (Hospital 12 de Octubre in Madrid). Clinical evaluation and laboratory investigations were scheduled to be performed every 3 months. The most recent CD4 and plasma viral loads were evaluated. Viral loads were considered undetectable when there were less than 300 copies/ml at the last evaluation. RESULTS: Sixty-six HIV-1-infected children who were followed-up to January 2002 were analyzed. All the children acquired the infection through vertical transmission except one, in whom the mode of transmission was unknown. The median age was 111 months (18-216). Twenty children were category C. The median CD4 cell count was 953 cells/mm3 (276-3137), 28 % +/- 8 (12.42). One child was receiving no therapy, four were on combination therapy with two nucleoside reverse transcriptase inhibitors (NRTI) and 61 were receiving highly active anti-retroviral therapy (HAART). Twenty-seven children (44 %) were receiving the first HAART regimen, 23 the second, and 11 had already been switched more than twice. Overall, 37 of the 61 patients receiving HAART had an undetectable plasma viral load. CONCLUSIONS: Most children in our study had gone through several antiretroviral regimens, although not all children were being treated with HAART. Fifty-six percent of the patients with HAART had an undetectable plasma viral load. However, new complications associated with this therapy have begun to appear.

Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.

Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.

[SEIP-SERPE-SEOP Consensus document on the treatment of uncomplicated acute osteomyelitis and septic arthritis]. / Documento de consenso SEIP-SERPE-SEOP sobre el tratamiento de la osteomielitis aguda y artritis séptica no complicadas.

This is a Consensus Document of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediatrica), Spanish Society of Paediatric Rheumatology (Sociedad Española de Reumatología Pediátrica) and the Spanish Society of Paediatric Orthopaedics (Sociedad Española de Ortopedia Pediátrica), on the treatment of uncomplicated acute osteomyelitis and septic arthritis. A review is presented on the medical and surgical treatment of acute osteoarticular infection, defined as a process with less than 14 days of symptomatology, uncomplicated and community-acquired. The different possible options are evaluated based on the best available scientific knowledge, and a number of evidence-based recommendations for clinical practice are provided.

[SEIP-SERPE-SEOP Consensus Document on aetiopathogenesis and diagnosis of uncomplicated acute osteomyelitis and septic arthritis]. / Documento de Consenso SEIP-SERPE-SEOP sobre etiopatogenia y diagnóstico de la osteomielitis aguda y artritis séptica no complicadas.

This is a Consensus Document of the Sociedad Española de Infectología Pediátrica, Sociedad Española de Reumatología Pediátrica and Sociedad Española de Ortopedia Pediátrica on the aetiology and diagnosis of uncomplicated acute osteomyelitis and septic arthritis. A review is presented of the aetiopathogenesis and pathophysiology of acute osteoarticular infection defined as a process with less than 14 days of symptomatology, uncomplicated, and community-acquired. The diagnostic approach to these conditions is summarised based on the best available scientific knowledge. Based on this evidence, a number of recommendations for clinical practice are provided.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

Subjective global assessment of nutritional status: further validation.

Subject global assessment of nutritional status was performed on 175 patients admitted to the medical-surgical gastroenterology service of a general hospital by a first-year resident and a specialist in clinical nutrition who were not aware of each other's evaluation. Patients were classified as well nourished or moderately or severely undernourished. Simultaneously, anthropometry was performed, serum albumin measured, and two units of PPD inoculated. A 79% concordance between the global subjective assessments made by the residents and the specialists was found. Patients in the three groups had significantly different weight, midarm circumference, triceps skinfold, and serum albumin values, whereas the total lymphocyte count and the percentage of negative PPD reactions were not significantly different. Subjective global assessment is a useful tool for the evaluation of nutritional status, even when used by inexperienced professionals.

Soft tissue conjunctivo-rhinostomy.

PURPOSE: To evaluate the results of implantation of a tubular prosthesis between the medial palpebral canthus and the nasal fossa, through the soft tissues of the face, in cases of irrecuperable damage of the lacrimal canaliculi. MATERIAL AND METHODS: Fifty eyes with canalicular destruction were operated, placing a silicone and Pyrex tubular prosthesis between the lacrimal caruncle and the nasal vestibulum, running almost vertically through the soft tissues of the face, without osteal perforation. RESULTS: Lacrimal flow was restored in 47 cases. There were three cases of dislocation of the prosthesis, three infections and five papillomata. CONCLUSIONS: Vertical conjunctivo-rhinostomy without osteal perforation is an easy and efficient solution for irrecuperable occluded canaliculi.

Congenital facial palsy and crossed facial nerve grafts: age and outcome.

Crossed facial nerve grafts for treating unilateral permanent facial palsy in association with hemifacial microsomia were studied in 18 patients, ages ranging from 2 months to 10 years. Patients were divided into groups according to the age at the time of indication of surgery. It is concluded that crossed nerve grafting for facial palsy associated with hemifacial microsomia appears to be an adequate procedure especially when the surgery is indicated soon after birth.

[Chronic granulomatous disease and pulmonary nocardiosis]. / Enfermedad granulomatosa crónica y nocardiosis pulmonar.

A 19-years-old male was admitted for left bilobar pneumonia. All microbiologic studies in blood and in several samples obtained by bronchoscopy were negative. The patient worsened progressively despite antibiotherapy of a wide spectrum. A fine needle transparietal puncture was performed. The cultures of the sample were positive for Nocardia asteroides, a positive catalase germ. Immunologic studies initiated after this time showed negative tetrazolium nitroblue test, the results of which led to the diagnosis of chronic granulomatous disease. This disease is very infrequent and the polymorphonuclear leukocytes are genetically incapable of producing peroxides whose absence impedes lysis of the positive phagocytic catalase germs with which a histologic reaction is produced in the form of granulomas from which the name of the disease is derived.

[Access to essential drugs in developing countries]. / El acceso a los medicamentos esenciales en los países pobres.

Every year infectious diseases kill about 13 million people, about 30.000 deaths a day. Almost half of the victims are children younger than 5 years old, most of them belong to developing countries. Most of the premature deaths and the incapacity cases associated to infectious diseases could be avoided if the poor had access to medicines. In the developing world, the poverty of the families, the inappropried public expense and the lack of sanitary infrastructures get together to leave out of the reach of the poor the possibility of an adequate medical treatment. According to World Health Organization (WHO) in the developing countries about 2,000 million people lack access to essential medicines. The new patent rules of the World Trade Organization (WTO) will reduce even more access to essential medicines to the poor. Granting trade exclusivity rights to the owners of the patents for a period of at least 20 years limits the right of the governments to allow production, trade and importation of low cost copies (generics) of patented drugs. It is not a theoretical or far away menace. The application of these more strict rules has all ready caused serious problems to developing countries producers of generics as India or Brazil or to importers of these as South Africa or Kenya. They have been press, taken to court and threaten of sanctions by the pharmaceutical industry and some developed countries governments. The decision of some developing countries to fight for their most needed people's health added to the international campaign for the access to essential medicines defended by some non governmental organizations like Act Up, Treatment Action Campaign, Doctors Without Borders and Intermon Oxfam have implied small victories on behalf of the poor countries access to medicines. But deeper changes in the patent rules and the investigation of the diseases of the developing world are needed to improve health in the developing countries.

[Voltage sources analysis in studies with foramen ovale electrodes]. / Análisis de fuentes de voltaje en estudios con electrodos de foramen oval.

INTRODUCTION: Paroxysmal activity in medial temporal lobe epilepsy is originated in either hippocampal or parahippocampal regions. This activity can be directly recorded by foramen ovale electrodes. That paroxysmal activity will start from irritative or ictal areas. However, anatomo-functional relations between both regions are still debated. OBJECTIVE: We describe a new physical very simple model which allows to directly analysis the anatomo-physiological relations between sources for interictal and ictal areas. RESULTS: 1) The mathematical model allows to fit with minimum error and great precision the voltage sources originated from monopoles. 2) We can obtain this degree of precision with a matrix using an internodal distance of 0.1 mm (300x200 nodes) 3) Triplets of potentials with double sources with equal or specially with inverse charges have bigger error than monopolar charges. 4) Fitting real data obtained from a patient shows an error of 0.29 +/- 0.17% for interictal and 0.54 +/- 1.22% and 2.84 +/- 3.00% for two seizures (mean +/- SD). CONCLUSIONS: This model allows directly to know the relative anatomo-physiological relations between interictal and ictal sources in MTLE, which have a very important implications so for patho-physiological as therapeutics and outcome implications.

[Localization of the epileptogenic zone by analysis of electroencephalographic dipole]. / Localización de la zona epileptógena mediante el análisis de dipolos electroencefalográficos.

INTRODUCTION: In partial epilepsy with seizures which are resistant to drug treatment, better results may be obtained with surgery. This follows thorough assessment to identify the area of the brain responsible for the origin of the seizures, or the epileptogenic zone (EZ), and show that surgical operation will not cause neurological or cognitive damage which might handicap the patient. OBJECTIVE: This study analyses the value in diagnosis of electroencephalographic dipoles in delimitation of the EZ in patients with refractory partial epilepsy who are candidates for surgical treatment. PATIENTS AND METHODS: In 43 patients we made EEG recordings whilst at rest with their eyes shut during 15 minutes. The signal was analysed by digital EEG apparatus and a map drawn of cerebral electrical activity based on the maximum average amplitude of the epileptic spikes. The electric dipole equivalent to epileptiform activity between seizures was obtained using the programme for analysis of electroencephalographic sources BESA. The localization of the EZ by means of the dipole was compared with the results of EEG, MR, SPECT and seizure video-EEG using intracranial electrodes. RESULTS: The results of this study show that the dipole model used is highly sensitive for localization of EZ, and in cases in which the dipole and MR coincided, its sensitivity is similar to that of video-EEG during seizures. CONCLUSIONS: The model of dipole used in this study is of great help when indicating surgery for patients with drug-resistant epilepsy.

[Pleural effusion due to Listeria monocytogenes. A case report and review of the literature]. / Derrame pleural por Listeria monocytogenes. Presentación de un caso y revisión de la literatura.

The infection caused by Listeria monocytogenes is a relatively common condition in immunosuppressed patients. The most frequent presentation in adults are sepsis and meningitis. Pleural fluid infection due to this pathogen is a rare finding in the literature. Most cases are found in immunosuppressed patients, particularly in those with haematologic malignancies. We report one case of pleural fluid infection due to Listeria monocytogenes in a patient with hepatic cirrhosis (the third case in the literature). We also review the seventeen cases previously reported and describe the clinical manifestations, its immunosuppression states relationship, the treatment of choice and the mortality.