The Effect of Lipofilling and Platelet-Rich Plasma on Patients with Moderate-Severe Vulvar Lichen Sclerosus who were Non-Responders to Topical Clobetasol Propionate: A Randomized Pilot Study.

BACKGROUND: The first-line treatment for vulvar lichen sclerosus (VLS) is 3 months of topical corticosteroid therapy. However, limited evidence is available concerning the use of fat grafting and platelet-rich plasma as a second-line treatment for patients who do not respond to first-line treatment. METHODS: This prospective single-center randomized pilot trial included 20 patients with a clinical and histological diagnosis of moderate to severe VLS. The patients in the treatment group (TG) received two infiltrations (at 3-month intervals) of nanofat mixed with platelet-rich plasma (PRP) into the vulvar area, while the control group (CG) received standard topical corticosteroid therapy. Fat was aspirated from the medial thigh or lower abdomen regions. Microfat was obtained after centrifugation and was emulsified to obtain a nanofat suspension. Treatment efficacy was determined by measuring changes in the vulvar skin elasticity, histopathology, and clinical signs, symptoms, and patient quality of life at after 1 year. RESULTS: A total of 19 patients were finally assessed (9 TG and 10 CG). At the end of the study (1 year), there had been no significant improvement in vulvar skin elasticity. However, patients in the TG showed a significant improvement in their symptoms (itching, pain, burning, and dyspareunia) and clinical signs (cervical erosions, fissures, stenosis, and leukoderma). Analysis of skin biopsies revealed a significant decrease in all inflammatory cell types in the TG. No adverse events related to the autologous treatment were recorded. CONCLUSIONS: Compared with topical corticosteroids, two infiltrations delivered 3 months apart decreased the inflammation of the vulva and improved most of the clinical signs and symptoms associated with VLS. Nonetheless, no improvement in vulvar skin elasticity was derived from the autologous treatment. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

What is the role of real time PCR in the follow up of patients with chronic Chagas' disease? / ¿Cuál es el papel de la PCR en tiempo real en el seguimiento de pacientes con enfermedad de Chagas crónica?

No disponible

Brote de neumonía por Chlamydia psittaci en la Región de Murcia / Outbreak of Chlamydia psittaci pneumonia in the Region of Murcia

No disponible

The Clinical and Parasitologic Follow-up of Trypanosoma cruzi-infected Children in a Nonendemic Country.

BACKGROUND: Chagas disease has become a global health problem, with the pediatric population being especially vulnerable. Our aim was to describe the clinical-epidemiologic aspects of disease in this population, as well as tolerance and adherence to treatment and the subsequent evolution of the disease. METHODS: A prospective study involving 949 children 0-14 years of age screened from 2007 to 2018. Diagnosis was performed by polymerase chain reaction and/or microhematocrit in <1-year-old children or serology in those ≥1 year of age. After diagnosis, children were examined for the clinical manifestation of Chagas disease and were treated with benznidazole. Treatment response was monitored by polymerase chain reaction and serology. RESULTS: Forty children were infected (4.2% of the population screened). Twelve children were diagnosed during the acute phase (≤1-year-old), 3 of whom were symptomatic, and 28 (4- to 14-year-olds) were in the chronic phase: 18 in the indeterminate phase and 10 presented cardiac and/or digestive involvement. Regarding treatment, 10 (25.6%) children had side effects (6 mild, 2 moderate and 2 severe reactions), leading to treatment interruption in 3 of them. No side effects were detected in ≤1-year-old children (P < 0.05). Cure was confirmed in 29.4% of the children during follow-up, and the age of the children at treatment (≤1 year) was clearly associated with the effectiveness of treatment (P < 0.05). CONCLUSIONS: Effectiveness and safety of treatment were optimum in ≤1-year-old children. Increased side effects, cardiac and/or digestive disorder incidence and lower treatment effectiveness were detected in older children, highlighting the need for early screening.

An observational longitudinal study to evaluate tools and strategies available for the diagnosis of Congenital Chagas Disease in a non-endemic country.

OBJECTIVES: Congenital Chagas Disease (CCD) has become a global health problem. Early diagnosis and treatment is essential for the cure of the disease. Our aim was to evaluate techniques and samples used for the diagnosis of CCD in order to improve diagnostic strategies. METHODS: A total of 181 children born in Spain from Latin American Chagas-infected mothers were consecutively enrolled and studied by microhematocrit, PCR and serology tests at 0-2, 6 and 9-12 months of age and followed up when it was required. Samples of cord blood and peripheral blood were collected for T. cruzi detection by PCR. Parasite culture was performed in patients with a positive PCR. RESULTS: Of 181 children, 7 children (3.9%) were lost to follow-up. A total of 174 children completed follow-up, 12 were diagnosed with CCD (6.9%) and 162 (93.1%) as uninfected children (negative serology tests at the end of the follow-up). Traditional parasitological diagnosis by microhematocrit had a poor performance (sensitivity was 10%), while PCR in peripheral blood showed high sensitivity (90.9%) and specificity (100%), allowing the early diagnosis of 9 infected children during the first 6-months-old. In the other 3 congenital cases, diagnosis was only possible at 12 months by serological and molecular techniques. However, PCR in cord blood showed low sensitivity (33.3%) and less specificity (96.4%) for the diagnosis. CONCLUSION: PCR in peripheral blood has proven to be the most adequate strategy for the diagnosis of CCD, allowing an early and reliable diagnosis.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Risk of postoperative morbidity in patients having bowel resection for colonic Crohn's disease.

BACKGROUND: The aim of the present multicenter study was to analyze the incidence and risk factors associated with postoperative morbidity in patients who had colorectal resection for colonic Crohn's disease. METHODS: Consecutive patients undergoing colorectal resection for colonic Crohn's disease at seven surgical units in 1992-2017 were included. Exclusion criteria were: proctectomy for perianal disease, surgery for cancer, previous colectomies, surgery before 1998. Abdominal colectomy and proctocolectomy were defined as extended resections; all other operations were classified as segmental resections. Postoperative intraabdominal septic complications (IASC) were: anastomotic leaks, peritonitis and abscess. RESULTS: One hundred ninety-nine patients met the inclusion criteria: 116 patients had segmental resections and extended resections were performed in 83 patients. An anastomosis was constructed in 122 patients and an additional stoma was formed in 15 of those cases. Segmental resections were performed significantly more frequently in stricturing or penetrating disease (93% vs. 61%, p < 0.001) and were completed by an anastomosis more often than extended resections (78% vs. 37%, p < 0.001). The overall IASC rate was 17%. On multivariate analysis, formation of an anastomosis (Hazard ratio 2.9; 95% CI 1.1-7.7; p = 0.036) and preoperative hemoglobin level of < 10 g/dl (Hazard ratio 3.1; 95% CI 1.1-9.1; p = 0.034) were associated with an increase of postoperative IASC rate. Preoperative medication did not influence postoperative outcome. CONCLUSIONS: Severe preoperative anemia is associated with an increased postoperative morbidity. Resections completed by an anastomosis pose an increased postoperative complication risk in patients with colonic Crohn's disease as compared to resections without an anastomosis.

Alpha-defensins (α-Defs) in Crohn's disease: decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility.

An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyse a potential epigenetic mechanism of α-Def expression. Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD) and from two control groups (healthy controls and non-CD-aetiology ileitis patients). Plasma α-Defs 1-3 and 4 were detected by enzyme-linked immunosorbent assay (ELISA); α-Def 5 by immunolocalization. Methylation analysis of the α-Def 5 gene was performed using the MassARRAY EpiTYPER system. Plasma α-Defs 1-3 concentrations were significantly higher in aCD with ileal involvement (L1, L3) versus iCD or the control groups. The α-Defs 1-3 concentrations were also similar to healthy controls in patients with non-CD ileitis. There was a significant positive correlation between plasma α-Defs 1-3 levels in aCD and the endoscopic index, as well as with C-reactive protein (CRP) levels. The immunopositivity scoring showed significantly reduced α-Def 5 expression in ileal inflamed (aCD) versus non-inflamed mucosa (iCD and healthy controls). The α-Def 5 gene showed a higher methylation status in CD patients than controls, regardless of the inflammation. Plasma α-Defs 1-3 concentrations correlate with the degree of inflammation and appear to be specific biomarkers of ileal-CD at diagnosis. Ileal α-Def 5 expression is down-regulated permanently by methylation.

Perceived efficacy and satisfaction of patients with subcutaneous hypoallergenic high-dose house dust mite extract.

SUMMARY: The efficacy and safety of subcutaneous immunotherapy with modified, high-dose, major allergen house dust mite extract is widely supported by double-blind, placebo-controlled studies. However, little is known regarding patient-perceived efficacy and satisfaction. An observational, retrospective, multicentre study in patients treated with Acaroid® was conducted to assess the efficacy and degree of satisfaction of the patients after the first six months of treatment with it. All the clinical study procedures were performed according to the routine clinical practice. This study demonstrates that Acaroid® is effective and well tolerated. The patients' condition demonstrated a clear and marked improvement in the first 6 months after treatment initiation. Patients treated with Acaroid® were very satisfied, with a correlation to improvement in patient-perceived symptoms and the administration of treatment by a healthcare professional.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Standardization of the homogeneous mobility shift assay protocol for evaluation of anti-infliximab antibodies. Application of the method to Crohn's disease patients treated with infliximab.

BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.

1-Butanol absorption in poly(styrene-divinylbenzene) ion exchange resins for catalysis.

The swelling behaviour of poly(styrene-co-divinylbenzene), P(S-DVB), ion exchange resins in 1-butanol (BuOH) has been studied by means of atomistic classical molecular dynamics simulations (MD). The topological characteristics reported for the resin in the dry state, which exhibited complex internal loops (macropores), were considered for the starting models used to examine the swelling induced by BuOH contents ranging from 10% to 50% w/w. Experimental measurements using a laser diffraction particle size analyzer indicate that swelling causes a volume variation with respect to the dry resin of 21%. According to MD simulations, such a volume increment corresponds to a BuOH absorption of 31-32% w/w, which is in excellent agreement with the indirect experimental estimation (i.e. 31% w/w). Simulations reveal that, independently of the content of BuOH, the density of the swelled resin is higher than that of the dry resin, evidencing that the alcohol provokes important structural changes in the polymeric matrix. Thus, BuOH molecules cause a collapse of the resin macropores when the content of alcohol is ≤20% w/w. In contrast, when the concentration of BuOH is close to the experimental value (∼30% w/w), P(S-DVB) chains remain separated by pores faciliting the access of the reactants to the reaction centers. On the other hand, evaluation of both bonding and non-bonding interactions indicates that the mixing energy is the most important contribution to the absorption of BuOH into the P(S-DVB) resin. Overall, the results displayed in this work represent a starting point for the theoretical study of the catalytic conversion of BuOH into di-n-butyl ether in P(S-DVB) ion exchange resins using sophisticated electronic methods.

Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease.

The altered expression of micro-RNA (miRNA) has been associated with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to establish specific miRNA expression patterns in the serum and mucosa of inflammatory bowel disease (IBD) patients (UC and CD with colonic involvement) at different stages of the disease. Serum and biopsies from nine active CD (aCD), nine inactive CD (iCD), nine active UC (aUC) and nine inactive UC (iUC) and serum from 33 healthy subjects were collected. Up to 700 miRNAs were evaluated by the TaqMan human miRNA array. The ΔCt values were obtained using the mean expression values of all expressed miRNAs in a given sample as a normalization factor for miRNA real-time quantitative polymerase chain reaction data. The levels of serum miRNAs in CD and UC patients were different to healthy subjects. Thirteen serum miRNAs were expressed commonly in CD and UC patients. Two miRNAs were higher and four miRNAs were lower in the serum of aCD than iCD. No serum miRNA was regulated exclusively in aUC compared with iUC patients. Four miRNAs were higher and three miRNAs were lower in the mucosa of aCD than iCD. Two miRNAs were higher and three miRNAs were lower in the mucosa of aUC than iUC. No serum miRNAs coincided with tissue miRNAs in aCD and aUC patients. Our results suggest the existence of specific miRNA expression patterns associated with IBD and their different stages and support the utility of miRNA as possible biomarkers. This pilot study needs to be validated in a large prospective cohort.

[Diagnosis and treatment of Chagas disease]. / Diagnóstico y tratamiento de la enfermedad de Chagas.

Trypanosoma cruzi infection, or Chagas disease, was discovered more than 100 years ago by Carlos Chagas. Although the infection kills more than 15,000 people each year, it is still classified as a neglected tropical disease. Today, this disease affects eight million people in 21 Latin American countries and, due to immigration, is also present in non-endemic countries. In recent years, the size of the immigrant population with chronic imported forms of Chagas disease has increased in Spain. In addition, several cases of congenital transmission have been reported. Some patients have severe infection and require specialized treatment such as pacemaker implantation or even heart transplantation, representing a considerable clinical, social and economic burden, particularly in areas with a large immigrant population. Since the 1960s, the only drugs available for the etiological treatment of this infection have been benznidazole and nifurtimox. Although new, more effective and better tolerated compounds are urgently needed, treatment with these trypanocidal drugs is recommended in both the acute and chronic stages of Chagas disease. New strategies for diagnosis and infection control in chronically infected patients have recently been reported, allowing the effectiveness of treatments to be assessed.

Diagnóstico y tratamiento de la malaria: análisis de la cohorte de pacientes ingresados en un hospital terciario (1998-2010) / Malaria diagnosis and treatment: analyse of a cohort of hospitalised patients at a tertiary level hospital (1998-2010)

Introducción. El aumento de los viajes internacionales y del número de inmigrantes de zonas donde la malaria es endémica hace que esta infección cada vez sea más frecuente en nuestro medio. El objetivo de este estudio es la descripción de una cohorte de pacientes ingresados por malaria: características epidemiológicas, clínicas y microbiológicas, quimioprofilaxis recibida y tratamiento antipalúdico prescrito. Métodos. Estudio descriptivo retrospectivo de los pacientes ingresados por malaria entre enero de 1998 y diciembre de 2010 en el Hospital Universitario Virgen de la Arrixaca (Murcia). Resultados. Ingresaron 51 casos de malaria; 78,3% eran inmigrantes, de los cuales el 65% residía en España y viajaron a sus países de origen para estancias cortas. El 74,5% adquirieron la infección en África central y occidental, y Plasmodium falciparum fue identificado en la mayoría de los casos (88%). Sólo 4 pacientes tomaron quimioprofilaxis antimalárica, pero ninguno completó la pauta. El tratamiento más empleado fue la combinación quinina y doxiciclina (64,7%). Se administró de manera incorrecta el tratamiento antimalárico en 9 pacientes (17,6%). Al menos encontramos un criterio de malaria severa en el 23,5% de los casos; sin embargo, la evolución clínica fue buena en todos los casos y ningún enfermo falleció. Conclusiones. La mayoría de los casos de malaria que ingresan en nuestro hospital son inmigrantes que viajan a sus países de origen para estancias cortas y no toman la quimioprofilaxis, aumentando considerablemente el riesgo de adquirir malaria. Además, la administración de un tratamiento inadecuado es relativamente frecuente en el manejo de pacientes con malaria importada(AU)

Introduction. The increasing frequency of malaria infection in our area is due to the rise in international travel and immigration from endemic malaria areas. The aim of this study is to describe the chemoprophylaxis taken and treatment given as well as the clinical, epidemiological and microbiological characteristics for those patients admitted to our hospital with malaria. Methods. A retrospective study of patients with malaria admitted to the Hospital Virgen de la Arrixaca, between January 1998 and December 2010, was carried out. Results. During this period, fifty one cases of malaria we- re diagnosed. 78.3% of them were immigrants of whom 65% resided in Spain and had travelled to their country of origin for a short stay. Seventy four per cent acquired the infection in central and west Africa, and Plasmodium falciparum was responsible for the majority of the cases (88%). Only four patients had taken antimalarial chemoprophylaxis but none correctly. The most frequently treatment used was a combination of quinine and doxycicline (64.7%). Inappropriate anti-malarial treatment occurred in 9 patients (17.6%). At least one indicator of severe malaria was established in 23.5% of the cases; however, the clinical outcome was successful in every case and no patient died. Conclusions. Imported malaria is observed mostly among immigrants who travel to their countries of origin for a short stay and do not take anti-malarial prophylaxis, increasing the risk of acquiring malaria. Inappropriate malarial treatment is relatively frequent in the case management of imported malaria(AU)