Elastic and inelastic diffraction changes upon variation of the relative humidity environment of PurE crystals.

The different changes observed in the diffraction patterns of three different crystal forms (hexagonal, trigonal and monoclinic) of PurE (EC 4.1.1.21), an enzyme from the purine-biosynthesis pathway of Bacillus anthracis, upon a wide range of changes in the relative humidity environment of the crystals are documented. In addition, the changes in the unit-cell parameters, volume and bulk solvent in the three different crystal forms were systematically followed. In an attempt to explain the elastic (P6(5)22) and inelastic (P3(1)21) changes in the diffraction pattern, refined structures of the three different crystal forms determined at 100 K are presented, with particular emphasis on the tertiary and quaternary structural differences, crystal packing, intermolecular and intramolecular interactions and solvent structure. The refined structures show that the precipitant salts, solvent structure (both ordered and bulk) and conformation of the C-termini all play a role in creating a unique cement at both the intramolecular and intermolecular contacts of the different crystal forms. It is suggested that it is the combination of polyethylene glycol and the structure of the ordered water molecules (first and second layers) as well as the structure of the bulk solvent that are the critical factors in the plasticity of the hexagonal crystal packing as opposed to the inelastic responses of the lower symmetry forms.

Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution. / Cistitis hemorrágica tras trasplante alogénico de progenitores hematopoyéticos: experiencia en un centro oncológico pediátrico.

OBJECTIVE: To analyze the risk factors associated with hemorrhagic cystitis (HC) severity and the treatment strategies available in HC patients following allogeneic hematopoietic stem cell transplantation (AHSCT). MATERIALS AND METHODS: A retrospective study of medical records was carried out. Patients with HC following AHSCT treated from 2017 to 2021 were divided into two groups according to severity -mild and severe. Demographic data, disease-specific characteristics, urological sequelae, and overall mortality were compared between both groups. The hospital's protocol was used for patient management. RESULTS: 33 episodes of HC were collected in 27 patients, 72.7% of whom were male. HC incidence following AHSCT was 23.4% (33/141). 51.5% of HCs were severe (grades III-IV). Severe graft host disease (GHD) (grades III-IV) and thrombopenia at HC onset were associated with severe HC (p= 0.043 and p= 0.039, respectively). This group had longer hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization, but only 1 case needed percutaneous cystostomy. None of the patients with mild HC required catheterization. No differences were found in terms of urological sequelae or overall mortality. CONCLUSIONS: Severe HC could be predicted thanks to the presence of severe GHD or thrombopenia at HC onset. Severe HC can be managed with bladder catheterization in most of these patients. A standardized protocol may help reduce the need for invasive procedures in patients with mild HC.

OBJETIVO: Analizar factores de riesgo asociados a la gravedad de la cistitis hemorrágica (CH) y estrategias de tratamiento en pacientes con CH tras trasplante alogénico de progenitores hematopoyéticos (TAPH). MATERIAL Y METODOS: Estudio retrospectivo de historias clínicas. Los pacientes con CH tras TAPH tratados entre 2017 y 2021 se dividieron en dos grupos según la gravedad del cuadro (leve y grave). Se compararon datos demográficos, características específicas de la enfermedad, secuelas urológicas y mortalidad global entre ambos grupos. Se utilizó el protocolo del hospital para el manejo de los pacientes. RESULTADOS: Se recogieron 33 episodios de CH en 27 pacientes, de los cuales el 72,7% fueron varones. La incidencia de CH tras TAPH fue del 23,4% (33/141). El 51,5% de las CH fueron graves (grados III-IV). La enfermedad de injerto contra huésped (EICH) grave (grados III-IV) y la trombopenia al inicio se asociaron a CH grave (p= 0,043 y p= 0,039, respectivamente). Este grupo tuvo mayor tiempo de hematuria (p< 0,001) y necesitó más transfusiones de plaquetas (p= 0,003). Además, el 70,6% precisó sondaje vesical, pero solo un caso cistostomía percutánea. Ningún paciente con CH leve precisó sondaje. No hubo diferencias en las secuelas urológicas ni en la mortalidad global. CONCLUSIONES: Una CH más grave podría predecirse por la presencia de EICH grave o trombopenia al inicio del cuadro. La CH grave puede manejarse con sondaje vesical en la mayoría de estos pacientes. Seguir un protocolo estandarizado puede reducir la necesidad de procedimientos invasivos en pacientes con CH leve.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

[Imported malaria in adults. Clinical, epidemiological and analytical features]. / Paludismo importado en adultos. Perfil clínico, epidemiológico y analítico.

INTRODUCTION: Up to now, the epidemiological and clinical features of imported malaria in Spain have been described in small series from general hospitals. Almost all diagnosis had been made based on symptomatic patients. The aim of this study has been to determine the epidemiological, clinical and laboratorial characteristics of imported malaria in a Reference Unit for Tropical Diseases. PATIENTS AND METHODS: We performed a cross-sectional, observational and retrospective study. The series consisted of patients diagnosed of malaria who had been attended at the Hospital Carlos III from January 1, 2002 to December 31, 2007. RESULTS: We identified 484 episodes of malaria, of which 398 cases were included in the analysis. Almost 50% of the patients were natives of endemic areas, while the rest were native-travelers or travelers. Most cases (88-98% according to the group) had not taken malaria chemoprophylaxis correctly when indicated. At the time of diagnosis, 30.4% of patients were asymptomatic and 28.1% of asymptomatic patients had anemia, 19.8% thrombocytopenia, 14% leukopenia, 5% hypocholesterolemia, 5% renal failure and 4.1% hypoglycemia. Low parasitemia was present in 97.5% of asymptomatic individuals compared to 80.5% of the symptomatic patients (P<0.001). DISCUSSION: Absence of chemoprophylaxis (or poor compliance) is the main reason for malaria in individuals traveling to endemic areas. Malaria must be ruled out in individuals coming from tropical countries with compatible symptoms, and it also should be suspected in certain groups of asymptomatic individuals with abnormal laboratorial parameters.

[Imported malaria and HIV infection in Madrid. Clinical and epidemiological features]. / Paludismo importado e infección por VIH en Madrid. Perfil clínico y epidemiológico.

INTRODUCTION: Few data are available in Spain data on human immunodeficiency virus (HIV) patients coinfected with malaria. This study has aimed to determine the epidemiological and clinical characteristics of imported malaria in patients coinfected with HIV. PATIENTS AND METHODS: A case-series retrospective study was performed using the patient's medical records. The study population consisted on patients diagnosed with malaria attended in our center from january 1, 2002 to december 31, 2007. RESULTS: A total of 484 episodes of malaria, 398 of which were included in this study, were identified. Co-infection with HIV was described in 32 cases. All of them occurred in individuals presumably with some degree of semi-immunity. In the coinfected group, there were 13 cases (40.6%) asymptomatic, whereas this event occurred in 99 cases of patients not coinfected (37.2%) (P=0.707). The greater presence of anemia in co-infected patients (62.5% vs 32.3% in non-coinfected [P=0.001]) stands out. CONCLUSIONS: In present study, the clinical presentation forms were similar, regardless of the presence or absence of HIV infection. Although the study population does not reflect all possible scenarios of malaria and HIV coinfection, our results indicate the reality of patients attended in the Autonomous Community of Madrid.

Epidemiology of Streptococcus pneumoniae and Staphylococcus aureus colonization in healthy Venezuelan children.

Streptococcus pneumoniae and Staphylococcus aureus cause significant morbidity and mortality worldwide. We investigated both the colonization and co-colonization characteristics for these pathogens among 250 healthy children from 2 to 5 years of age in Merida, Venezuela, in 2007. The prevalence of S. pneumoniae colonization, S. aureus colonization, and S. pneumoniae-S. aureus co-colonization was 28%, 56%, and 16%, respectively. Pneumococcal serotypes 6B (14%), 19F (12%), 23F (12%), 15 (9%), 6A (8%), 11 (8%), 23A (6%), and 34 (6%) were the most prevalent. Non-respiratory atopy was a risk factor for S. aureus colonization (p = 0.017). Vaccine serotypes were negatively associated with preceding respiratory infection (p = 0.02) and with S. aureus colonization (p = 0.03). We observed a high prevalence of pneumococcal resistance against trimethoprim-sulfamethoxazole (40%), erythromycin (38%), and penicillin (14%). Semi-quantitative measurement of pneumococcal colonization density showed that children with young siblings and low socioeconomic status were more densely colonized (p = 0.02 and p = 0.02, respectively). In contrast, trimethoprim-sulfamethoxazole- and multidrug-resistant-pneumococci colonized children sparsely (p = 0.03 and p = 0.01, respectively). Our data form an important basis to monitor the future impact of pneumococcal vaccination on bacterial colonization, as well as to recommend a rationalized and restrictive antimicrobial use in our community.

Humidity control can compensate for the damage induced in protein crystals by alien solutions.

The use of relative humidity control of protein crystals to overcome some of the shortcomings of soaking ligands (i.e. inhibitors, substrate analogs, weak ligands) into pre-grown apoprotein crystals has been explored. Crystals of PurE (EC 4.1.1.21), an enzyme from the purine-biosynthesis pathway of Bacillus anthracis, were used as a test case. The findings can be summarized as follows: (i) using humidity control, it is possible to improve/optimize the diffraction quality of crystals soaked in solutions of organic solvent (DMSO, ethanol) containing ligands/inhibitors; (ii) optimization of the relative humidity can compensate for the deterioration of the diffraction pattern that is observed upon desalting crystals grown in high salt; (iii) combining desalting protocols with the addition of PEG it is possible to achieve very high concentrations of weak ligands (in the 5-10 mM range) in soaking solutions and (iv) fine control of the relative humidity of crystals soaked in these solutions can compensate for the deterioration of crystal diffraction and restore `high-resolution' diffraction for structure-based and fragment-based drug design. It is suggested that these experimental protocols may be useful in other protein systems and may be applicable in academic or private research to increase the probability of obtaining structures of protein-ligand complexes at high resolution.

Utility of real-time PCR for the detection of Paracoccidioides brasiliensis DNA in the diagnosis of imported paracoccidioidomycosis.

An increase in immigration from endemic regions has resulted in a number of cases of paracoccidioidomycosis (PCM) being imported into Spain. A molecular diagnostic technique based on real-time PCR was developed for the detection of Paracoccidioides brasiliensis DNA in both culture and patients' clinical samples. A Molecular Beacon probe was used, labelled with FAM and directed at the ITS1 region of ribosomic DNA. The detection limit of the technique developed was 1 fg of fungal DNA per microl of sample. This procedure proved to be very reproducible and specific. The technique was tested with cultures of 12 clinical strains and on samples from two patients with proven PCM. Real-time PCR was positive for all the culture strains, as well as those from both patients. By samples, the technique was positive in sputum and tissue biopsies but less useful on blood samples. Samples were analyzed several months after patient treatment, detecting a small amount of fungal DNA in one respiratory sample. This technique of real-time PCR is a sensitive method for rapid diagnosis of paracoccidioidomycosis and could serve to monitor patients after treatment has begun.

Cistitis hemorrágica tras trasplante alogénico de progenitores hematopoyéticos: experiencia en un centro oncológico pediátrico / Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution

Objetivos: Analizar factores de riesgo asociados a la gravedad de lacistitis hemorrágica (CH) y estrategias de tratamiento en pacientes conCH tras trasplante alogénico de progenitores hematopoyéticos (TAPH).Material y métodos: Estudio retrospectivo de historias clínicas. Lospacientes con CH tras TAPH tratados entre 2017 y 2021 se dividieronen dos grupos según la gravedad del cuadro (leve y grave). Se compararon datos demográficos, características específicas de la enfermedad,secuelas urológicas y mortalidad global entre ambos grupos. Se utilizóel protocolo del hospital para el manejo de los pacientes. Resultados: Se recogieron 33 episodios de CH en 27 pacientes, delos cuales el 72,7% fueron varones. La incidencia de CH tras TAPH fuedel 23,4% (33/141). El 51,5% de las CH fueron graves (grados III-IV).La enfermedad de injerto contra huésped (EICH) grave (grados III-IV) yla trombopenia al inicio se asociaron a CH grave (p= 0,043 y p= 0,039,respectivamente). Este grupo tuvo mayor tiempo de hematuria (p<0,001)y necesitó más transfusiones de plaquetas (p= 0,003). Además, el 70,6%precisó sondaje vesical, pero solo un caso cistostomía percutánea. Ningún paciente con CH leve precisó sondaje. No hubo diferencias en lassecuelas urológicas ni en la mortalidad global. Conclusiones: Una CH más grave podría predecirse por la presenciade EICH grave o trombopenia al inicio del cuadro. La CH grave puedemanejarse con sondaje vesical en la mayoría de estos pacientes. Seguirun protocolo estandarizado puede reducir la necesidad de procedimientosinvasivos en pacientes con CH leve.(AU)

Objective: To analyze the risk factors associated with hemorrhagiccystitis (HC) severity and the treatment strategies available in HC patientsfollowing allogeneic hematopoietic stem cell transplantation (AHSCT). Materials and methods: A retrospective study of medical recordswas carried out. Patients with HC following AHSCT treated from 2017to 2021 were divided into two groups according to severity –mild andsevere. Demographic data, disease-specific characteristics, urologicalsequelae, and overall mortality were compared between both groups.The hospital’s protocol was used for patient management. Results: 33 episodes of HC were collected in 27 patients, 72.7% ofwhom were male. HC incidence following AHSCT was 23.4% (33/141).51.5% of HCs were severe (grades III-IV). Severe graft host disease(GHD) (grades III-IV) and thrombopenia at HC onset were associatedwith severe HC (p= 0.043 and p= 0.039, respectively). This group hadlonger hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization,but only 1 case needed percutaneous cystostomy. None of the patientswith mild HC required catheterization. No differences were found interms of urological sequelae or overall mortality. Conclusions: Severe HC could be predicted thanks to the presenceof severe GHD or thrombopenia at HC onset. Severe HC can be managedwith bladder catheterization in most of these patients. A standardizedprotocol may help reduce the need for invasive procedures in patientswith mild HC.(AU)

Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica / Pediatric perianal Crohn’s disease behavior in the era of biologic therapy

Objetivo del estudio: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. Métodos: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. Resultados: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. Conclusiones: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.(AU)

Aim of the study: To describe perianal Crohn’s disease behavior and the role of biological therapy in a sample of pediatric patients. Methods: A retrospective study of pediatric patients with Crohn’s disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. Results: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. Conclusions: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.(AU)

Unapparent hypoxanthine-guanine phosphoribosyltransferase deficiency.

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data. Patients with HPRT deficiency present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. We present a 9-year-old boy who experienced an episode of macroscopic hematuria with dysuria and left flank pain. He presented hyperuricemia and hyperuricosuria. HPRT and APRT activities were both normal in hemolysate; however, HPRT activity assayed in intact erythrocytes was 50% of control levels. A new missense point mutation c.424 A>G (T142A) was found in the HPRT1 gene. The apparent Michaelis constant (Km) for 5-phosphoribosyl-pyrophosphate assayed in patient hemolysate was 20-fold of control levels. In conclusion, we report a patient with HPRT deficiency who presented with both normal HPRT and APRT activity in hemolysate, in which the enzyme activity determined in intact erythrocytes was of diagnostic utility.

Electromechanical delay in the tibialis anterior muscle during time-varying ankle dorsiflexion.

We evaluated the electromechanical delay (EMD) for the tibialis anterior (TA) muscle during the performance of time-varying ankle dorsiflexions. Subjects were asked to track a sinusoidal trajectory, for a range of amplitudes and frequencies. Motor unit (MU) action potential trains were identified from surface electromyography (EMG) decomposition and summed to generate the cumulative spike train (CST). CST and the exerted force were cross-correlated to identify the delay between the CST and force, which was considered as an estimate of the EMD. The results showed that the EMD decreased logarithmically with the increase in the slope of the force produced.

Diagnosis of visceral leishmaniasis in HIV-infected individuals using peripheral blood smears.

OBJECTIVE: To compare the clinical and laboratory features of visceral leishmaniasis (kala-azar) in HIV-infected and non-infected subjects, and to determine the presence of Leishmania amastigotes in circulating leukocytes using peripheral blood smears. PATIENTS: Twenty-eight HIV-infected and six HIV-negative adult patients diagnosed as having kala-azar presenting at one institution over a 7-year period. METHODS: Retrospective review of clinical charts and re-examination of peripheral blood smears. RESULTS: There were no significant differences in the clinical presentation and laboratory features of HIV-positive and HIV-negative patients. However, Leishmania amastigotes were observed in circulating leukocytes in eight out of the 17 available peripheral blood smears (15 from HIV-infected patients). All eight individuals presenting with Leishmania in peripheral blood leukocytes were HIV-positive. CONCLUSIONS: Direct visualization of Leishmania amastigotes in leukocytes on peripheral blood smears enabled the diagnosis of kala-azar in a high proportion [eight out of 15 (53%)] of our HIV-infected patients.

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Evidence of HIV-2 infection in Equatorial Guinea (central Africa): partial genetic analysis of a B subtype virus.

PIP: A case of HIV-2 infection is described in a 35-year-old woman born in Malabo, Equatorial Guinea, who migrated to Madrid, Spain, in 1995. It was determined through questioning the woman that her only HIV-associated risk factor was unprotected heterosexual contacts in her country of origin. Her ex-husband, to whom she had been married for 18 years, was also from Equatorial Guinea and was known to have had multiple sex partners. The woman reported having had heterosexual encounters with five other partners in her native country, although less frequently than with her ex-husband. She was unaware of her sex partners' HIV serostatus and denied having had any sexual relations in Spain during her one-year current residency. The woman was in good health and presented with a CD4+ T cell count of 486 cubic millimeters. HIV-2 infection was identified using the Pepti-LAV immunoassay and Western blot. Isolation of the infecting virus was attempted by coculturing the patient's peripheral blood mononuclear cells (PBMCs) with PBMCs from an HIV-seronegative donor according to standard protocols for HIV isolation. Nested polymerase chain reaction was later conducted on some DNA from the woman's uncultured PBMCs. Phylogenetic analysis showed that the sequence data obtained clustered with the B subtype of HIV-2.^ieng

Renal tubular acidosis in the Silver-Russell syndrome.

Several patients with the Silver-Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO3- levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of < 2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and amino acids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non-acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow-up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients.

Visceral leishmaniasis in Angola due to Leishmania (Leishmania) infantum.

A 26-year-old man from Angola with no history of travel outside the country presented with typical symptoms of visceral leishmaniasis. The parasite was isolated and biochemically characterized using both kinetoplast DNA and nuclear DNA probes and showed a strong homology with Leishmania (Leishmania) donovani sensu lato (s.l.). When the nuclear DNA of the isolate was hybridized with a specific Leishmania (L.) infantum probe, the pattern obtained showed a clear signal with this species. To establish its identity more specifically, this isolate was typed using a 15-system isoenzyme panel and thick-starch gel electrophoresis, and was identified as L. (L.) infantum zymodeme 1 (MAD-1), the most widespread zymodeme in Mediterranean countries. One case of visceral leishmaniasis has been reported in Angola, but this case is the first report of L. (L.) infantum in Africa south of the equator.

Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.

The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed.