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Background: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort., Methods: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections., Results: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763)., Conclusions: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries., Methods: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram., Results: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram., Conclusions: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Laynez-Roldán et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria., Methods: A case-control study was conducted in Barcelona, from January 2011-January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers' performance was evaluated using multiple imputation models., Results: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64-0.94) and 0.80(95%CI 0.67-0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68-0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9-98.1) and 77.4% (95%CI 65.9-87.7), respectively., Conclusions: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction. The identification of enteropathogens is critical for the clinical management of patients with suspected gastrointestinal infection. The FLOW multiplex PCR system (FMPS) is a semi-automated platform (FLOW System, Roche) for multiplex real-time PCR analysis. Hypothesis/Gap Statement. FMPS has greater sensitivity for the detection of enteric pathogens than standard methods such as culture, biochemical identification, immunochromatography or microscopic examination. Aim. The diagnostic performance of the FMPS was evaluated and compared to that of traditional microbiological procedures. Methodology. A total of 10 659 samples were collected and analysed over a period of 7 years. From 2013 to 2018 (every July to September), samples were processed using standard microbiological culture methods. In 2019, the FMPS was implemented using real-time PCR to detect the following enteropathogens: Shigella spp. , Salmonella spp. , Campylobacter spp., Giardia intestinalis, Entamoeba histolytica, Blastocystis hominis, Cryptosporidum spp. , Dientamoeba fragilis , adenovirus, norovirus and rotavirus. Standard microbiological culture methods (2013-2018) included stool culture, microscopy and immunochromatography. Results. A total of 1078 stool samples were analysed prospectively using the FMPS from July to September (2019): bacterial, parasitic and viral pathogens were identified in 15.3, 9.71 and 5.29 % of cases, respectively. During the same period of 6 years (2013-2018), the proportion of positive identifications using standard microbiological methods from 2013 to 2018 was significantly lower. A major significant recovery improvement was observed for all bacteria species tested: Shigella spp./enteroinvasive Escherichia coli (EIEC) ( P <0.05), Salmonella spp. ( P <0.05) and Campylobacter spp. ( P <0.05). Marked differences were also observed for the parasites G. intestinalis , Cryptosporidium spp. and D. fragilis . Conclusion. These results support the value of multiplex real-time PCR analysis for the detection of enteric pathogens in laboratory diagnosis with outstanding performance in identifying labile micro-organisms. The identification of unsuspected micro-organisms for less specific clinical presentations may also impact on clinical practice and help optimize patient management.

Introduction : Strongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas, however, seroprevalence data are scarce in migrant populations, particularly for those coming for Asia. Methods : This study aims at evaluating the prevalence of S. stercoralis at the hospital level in migrant populations or long term travellers being attended in out-patient and in-patient units as part of a systematic screening implemented in six Spanish hospitals. A cross-sectional study was conducted and systematic screening for S. stercoralis infection using serological tests was offered to all eligible participants. Results : The overall seroprevalence of S. stercoralis was 9.04% (95%CI 7.76-10.31). The seroprevalence of people with a risk of infection acquired in Africa and Latin America was 9.35% (95%CI 7.01-11.69), 9.22% (7.5-10.93), respectively. The number of individuals coming from Asian countries was significantly smaller and the overall prevalence in these countries was 2.9% (95%CI -0.3-6.2). The seroprevalence in units attending potentially immunosuppressed patients was significantly lower (5.64%) compared with other units of the hospital (10.20%) or Tropical diseases units (13.33%) ( p < 0.001). Conclusions : We report a hospital-based strongyloidiasis seroprevalence of almost 10% in a mobile population coming from endemic areas suggesting the need of implementing strongyloidiasis screening in hospitalized patients coming from endemic areas, particularly if they are at risk of immunosuppression.

Background: Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions., Case Presentation: We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed., Conclusions: Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.

Malaria, arbovirus infection and travelers' diarrhea are among the most common etiologies of fever after a stay in the tropics. Because the initial symptoms of these diseases often overlap, the differential diagnostic remains a challenge. The aim of this study was to establish the effectiveness of platelet and leukocyte counts in the differential diagnosis of fever in the returning traveler. Between 2013 and 2016, patients with a clinical suspicion of malaria, who had thick blood smears performed were retrospectively included. The microbiological etiology of each episode was established based on molecular detection in the case of arbovirus infection, the detection of pathogens in stool samples for diarrhea and other gastrointestinal symptoms and the thick and thin blood smear results for malaria. A total of 1,218 episodes were included. Malaria, arbovirus infection, and diarrhea and other gastrointestinal symptoms caused 102 (8.4%), 68 (5.6%), and 72 (5.9%) episodes, respectively. The median platelet counts in malaria episodes were 89 × 10 9 /L and thrombocytopenia (< 150,000 × 10 9 platelets/L) yielded a 98% negative predictive value to predict malaria. The median leukocyte counts in arbovirus infection episodes were 3.19 × 10 9 /L and leucopenia (< 4 × 10 9 leukocytes/L) yielded a 97.9% negative predictive value to predict arbovirus infections. Platelet and leukocyte counts were not significantly altered in episodes caused by diarrhea and other gastrointestinal symptoms. Initial platelet and leukocyte counts might be useful for the clinical differential diagnosis of fever in the returning traveler. Although these results are insufficient to establish a diagnosis, they should be considered in the initial clinical assessment.

Background: Strongyloides stercoralis is a worldwide disseminated parasitic disease that can be transmitted from solid organ transplant (SOT) donors to recipients. We determined the serological prevalence of S. stercoralis among deceased individuals from endemic areas considered for SOT donation, using our institution's serum bank., Methodology: Retrospective study including all deceased potential donors from endemic areas of strongyloidiasis considered for SOT between January 2004 and December 2014 in a tertiary care hospital. The commercial serological test IVD-Elisa was used to determine the serological prevalence of S. stercoralis., Principal Findings: Among 1025 deceased individuals during the study period, 90 were from endemic areas of strongyloidiasis. There were available serum samples for 65 patients and 6 of them tested positive for S. stercoralis (9.23%). Only one of the deceased candidates was finally a donor, without transmitting the infection., Conclusions: Among deceased individuals from endemic areas considered for SOT donation, seroprevalence of strongyloidiasis was high. This highlights the importance of adhering to current recommendations on screening for S. stercoralis among potential SOT donors at high risk of the infection, together with the need of developing a rapid diagnostic test to fully implement these screening strategies., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Diarrhea is a frequent complication in hematologic patients, being an infectious cause frequently suspected. Rapid and accurate detection of gastrointestinal pathogens is vital in immunocompromised hosts. The aim of this study was to compare routine diagnostic methods versus a multiplex polymerase chain reaction (PCR) assay for the diagnosis of infectious diarrhea in immunocompromised hematologic patients., Material and Methods: We conducted a prospective observational study from March 2015 to January 2016 to compare conventional methods for the diagnosis of infectious diarrhea with FIlmArray GI Panel (BioFire-bioMérieux, France). Samples from adult immunocompromised hematologic patients with acute diarrhea were collected. In cases with discordant results, a second multiplex assay was performed (Allplex, Seegene, Korea). The result was considered positive or negative when the same result was obtained by at least two of the methods., Results: A total of 95 samples were obtained from 95 patients (median age of 52 years (46-64)). Sixty-one (64%) episodes were hospital-acquired and 34 (36%) were community-acquired diarrhea. Twenty-five (26%) patients had a positive microbiological result, being Clostridium difficile the most frequent pathogen, followed by Campylobacter spp and norovirus. The concordance between FilmArray methods was good (k = 0.79). The FilmArray GI panel showed a sensitivity of 95%, a specificity of 100% for positive results. The time required to obtain results was markedly reduced with the use of multiplex PCR methods., Conclusions: Multiplex molecular panels provide a rapid and sensitive tool for the diagnosis of infectious diarrhea, thereby allowing more timely clinical decisions in immunocompromised hematologic patients.

Background: There is little evidence regarding the management of refractory giardiasis after treatment with nitroimidazoles. This study estimates the proportion of persistent giardiasis in 3 hospitals in Barcelona, describes associated risk factors and genotype, and evaluates the efficacy rate of quinacrine in those with persistent giardiasis., Methods: A clinical, prospective, observational study was conducted in patients with giardiasis treated with nitroimidazoles. Those with persistent giardiasis were provided quinacrine. Molecular characterization of Giardia isolates was performed by polymerase chain reaction amplification of a fragment of tpi and bg genes., Results: Seventy-seven patients were recruited and treated with nitroimidazoles, and in 14 of 71 (20%) of patients followed up, Giardia persisted. Refractory giardiasis was associated with malaise (P = .007) and anorexia (P = .02), with previous giardiasis (P = .03), and with previous antibiotic (P = .02) or antiparasitic(P = .04) use. Quinacrine had an effectiveness rate of 100% in refractory giardiasis (n = 13; 95% confidence interval = 75-100). Molecular characterization showed that 17 (25%) Giardia isolates belonged to assemblage A, and 31 (43%) belonged to assemblage B. In refractory giardiasis, assemblage A and B were found responsible in 4 and 6 cases, respectively., Conclusions: Almost 20% of patients presented persistent giardiasis, belonging to both assemblages A and B, after nitroimidazole. Short course of quinacrine was effective in treating refractory cases. Further controlled studies should evaluate its efficacy and safety., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We report a severe Babesia microti infection in an immunocompetent patient diagnosed in Spain. A 66-year-old woman coming from USA presented with fever, thrombocytopenia, and multiorgan failure. Intraerythrocytic parasites were observed in Giemsa-stained peripheral blood smears and B. microti was first suspected by optical microscopy and afterward confirmed by specific polymerase chain reaction (PCR). Patient received antibiotic therapy, vital support measures and one red blood cell (RBC) exchange procedure. After 15 days, patient recovered and she was transferred to her reference hospital. This case report highlights the importance of clinical suspicion by physicians in non-endemic areas to diagnose this entity, the differential diagnosis with malaria infection, and the indication of RBC exchange as a therapeutic apheresis modality in the management of severe forms., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Cryptosporidium infection is a worldwide cause of diarrheal disease. To gain insight into the epidemiology of the infection in a certain geographic area, molecular methods are needed to determine the species/genotypes and subtypes., Methodology/principal Findings: From 2004 to 2009, 161 cryptosporidiosis cases were detected in two hospitals in Barcelona. Diagnosis was performed by microscopic observation of oocysts in stool specimens following modified Ziehl-Neelsen staining. Most cases (82%) occurred in children. The number of cases increased in summer and autumn. Molecular characterization of Cryptosporidium was performed in 69 specimens, and C. hominis and C. parvum were identified in 88.4% and 10.1% of the cases, respectively. C. meleagridis was detected in one specimen. Subtyping based on the gp60 polymorphism showed six subtypes, four C. hominis and two C. parvum. Subtype IbA10G2 was the most prevalent subtype corresponding to 90% of all C. hominis isolates. This is the first report on the distribution of specific Cryptosporidium subtypes from humans in Spain., Conclusions/significance: In our geographic area, the anthroponotic behavior of C. hominis, the lower infective dose, and the higher virulence of certain subtypes may contribute to the high incidence of human cryptosporidiosis caused by the IbA10G2 subtype. Further studies should include populations with asymptomatic shedding of the parasite.

Traveller's diarrhoea (TD) is the most common illness reported in international travellers. TD is caused by a wide range of pathogens, including bacteria, viruses and parasites. Multiplex PCR assays can be especially useful for studying the aetiology of TD. The first objective of this study was to evaluate the utility of the commercially available multiplex PCR (xTAG(®) Gastrointestinal Pathogen Panel (GPP)) for the diagnosis of TD. A total of 185 stool specimens obtained from 174 patients were processed using the GPP assay. This test detected 86 pathogens in 67 stool samples (67/185, 36.2%). Sixteen pathogens out of 86 were also detected by routine testing. The remaining pathogens (n = 70) required further confirmation by alternative techniques. Finally, 60 out of 70 pathogens were confirmed. The second objective of this study was to analyse the aetiology of TD based on the results obtained by the GPP test and routine methods. The primary pathogens causing TD were Shigella (24.2%) followed by enterotoxigenic Escherichia coli (ETEC) (23.2%), enteroaggregative E. coli (14.7%) and Giardia (13.7%). Significant regional differences were observed for ETEC with 19.4% of TD cases acquired in Africa, 11.3% in Asia and none in South Central (SC) America (p 0.01), Giardia was found in 1.5% of cases among those who had travelled to Africa, 14.1% of those who had travelled to Asia and 3% of those who had travelled to SC America (p 0.01). In conclusion, the GPP test improved the detection of enteropathogens and allowed better assessment of the aetiology of TD., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage., Methods: 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients., Principal Findings: G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients., Conclusions: The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated.

Persistence of giardiasis after some of the recommended drugs is occurring with increasing frequency. We describe the follow-up of four members of a family with giardiasis through microscopic observation, immunochromatography and PCRs of tpi and β-giardin genes. Three patients did not respond to tinidazole but they were cured after quinacrine. However, PCR became negative at 2 months after negativization of stools in two patients and after 1 year in one patient. In all cases Giardia assemblage B was characterized with high homology between all isolates. Further studies are needed to determine the value of PCR in the diagnosis of Giardia infections., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Drug failure is a common cause of symptom persistence after treatment of imported Giardia duodenalis. In this retrospective study we describe a high prevalence of refractory giardiasis in people attended in a travel clinic in Spain, especially those with infections acquired in Asia. Moreover, we discuss various treatment strategies to tackle G. duodenalis that is refractory to nitroimidazoles., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: It is unknown whether a Toxoplasma gondii-specific T cell response is restored after successful combined antiretroviral therapy (cART) in patients with AIDS and current or previous toxoplasmic encephalitis (TE)., Methods: We performed a multicenter cross-sectional study with 17 healthy T. gondii-positive human immunodeficiency virus (HIV)-1-uninfected individuals and 90 patients coinfected with HIV-1 and T. gondii distributed in 5 groups according to their CD4(+) T cell counts and T. gondii infection (with or without current or previous TE). We investigated the lymphocyte proliferative response (LPR) and interferon (IFN)-γ production in response to T. gondii soluble antigen extract (SATg) and as CD4(+) and CD8(+) T cell subsets., Results: SATg-specific LPR and IFN-γ production were not observed in many of the most immunosuppressed patients (CD4(+) T cell count, <200 cells/μL, with or without current or previous TE). By contrast, these responses occurred in a considerable percentage (LPR, 43%; IFN-γ production, 80%) of patients receiving successful cART (CD4(+) T cell count, >200 cells/μL) who presented with TE and had already stopped secondary TE prophylaxis. Similar results were found in immunocompetent asymptomatic patients who did not receive TE prophylaxis. The predictors of SATg-specific T cell responses and IFN-γ production were a cART-mediated increase in CD4(+) T cell count and LPR to phytohemagglutinin and viral suppression and a decrease in the activated (CD38(+)) CD8(+) T cell count, respectively., Conclusions: cART restores T. gondii-specific CD4 T cell responses in most patients with AIDS who had previous TE. Our data support the safety of withdrawing TE prophylaxis when the CD4(+) T cell count returns to levels >200 cells/μL.

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

Strongyloides stercoralis has a unique ability to replicate in the human host and lead to chronic infection that can persist for several decades. Thirty-three patients (10 travellers and 23 immigrants) with imported S. stercoralis infection were studied and clinical and epidemiological characteristics described. Only 16 patients (48.5%) reported symptoms, mainly of the gastrointestinal tract. Eosinophilia was present in 21 (63.6%) patients. Seven patients (21.2%) had an immunocompromising condition. Patients were classified into chronic asymptomatic infection (17/33, 51.5%), chronic symptomatic infection (11/33, 33.3%) and hyperinfection (5/33, 15.2%). Four of the latter (80%) had an immunocompromising condition. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. Diagnosis should always be sought in immunocompromised hosts., (Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Severe imported malaria is an important problem in many countries in which this disease is not endemic. This retrospective study describes the characteristics of 20 adults with severe imported malaria admitted to our intensive care unit from 1991 through 2007. All episodes were caused by Plasmodium falciparum and all patients had returned from sub-Saharan Africa, except for one transfusion recipient. All persons were considered non-immune, and none had taken appropriate chemoprophylaxis. The median time between the initiation of symptoms and the diagnosis was seven days. Five patients died (mortality rate = 25%). A higher frequency of unrousable coma and acidosis and a higher median Apache II score at admission was noted in the persons who died. Mortality by severe malaria remains high despite high quality management, which highlights the importance of chemoprophylaxis and early diagnosis and treatment.

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

A polymerase chain reaction (PCR)-based test for Pneumocystis jiroveci (formerly Pneumocystis carinii f. sp. hominis) might be an alternative to histologic diagnoses of P. jiroveci pneumonia (PCP). However, previously developed nested PCR methods tend to have low specificities (high false-positive rates). In this study, nested and quantitative real-time PCR methods for the amplification of the P. jiroveci DHPS (dihydropteroate synthase) gene were evaluated in a variety of stored clinical samples from Spain, South Africa, and Brazil. The sensitivities of both assays were high, ranging from 62.5% to 100% depending on the type of specimen. In a subset of 71 microscopically confirmed PCP cases and 70 negative cases, the sensitivities and specificities were 94% and 81% for nested PCR and 94% and 96% for real-time PCR, respectively. Real-time PCR has a statistically significantly better specificity than nested PCR (P = .015) and is likely to generate fewer false positives.

A single 40 mg/kg dose of praziquantel (PZQ) continues to be the standard treatment for schistosomiasis caused by S. mansoni and S. haematobium in all clinical settings. Experimental development of drug resistance and the recent isolation of S. mansoni strains with a natural tolerance to high doses of PZQ have raised concerns over the adequacy of such a dose. We describe two Spanish travelers with genitourinary schistosomiasis caused by S. haematobium in whom repeated standard treatment failed to clear the infection.

Introduction: Primaquine is now the only drug available to eradicate Plasmodium vivax malaria. The optimal dose of primaquine to prevent relapses of P. vivax remains under discussion., Clinical Cases: We describe three cases of P. vivax malaria from different geographical areas, in which a tolerance to standard doses of primaquine and, in some cases, to much higher doses has been observed., Comments: P. vivax tolerance to primaquine is an emerging problem in daily practice. Reassessment of the primaquine dose required to eradicate P. vivax intrahepatic hypnozoites is needed.

Background and Objective: Senegal is increasingly becoming a touristic target for many people. In 2000, there was a greater number of cases of malaria in patients from this country. Our objective was to analyze such increase, to describe the characteristics of these patients and to identify the reasons for it., Patients and Method: From 1999 to 2002 we prospectively collected the clinical and epidemiological data of all consecutive malaria cases seen in the Unit of Tropical Medicine of the Hospital Clinic (Barcelona, Spain)., Results: We attended 276 patients, 74 of them during 2000; of them, 17 had travelled to Senegal and Gambia. Their mean age was 36.58 (6.9) years and 12% were women. 59% patients were Spaniards, 35% were native of Senegal and 6% of Gambia. Reason of travel was tourism in 9 cases (53%) and a visit to the family in 7 cases (41%). Mean duration of the visit was 31 (20.6) days and only 17.6% patients did a right prophylaxis. Plasmodium falciparum was the commonest species (88%). The number of patients with malaria who had visited Senegal ranged from 6.6% in 1996 to 20% in 2000 to 6.3% in 2002 (p<0.05)., Conclusions: There was an unexpected increase of malaria imported from Senegal in 2000 in our Unit. Changes in both the dynamics of malaria transmission and tourism offers may account for an unsuspected increase of malaria cases.

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-alpha) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-alpha, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1beta, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-alpha levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).

The study presented here aimed to contrast the marked clinical differences in the presentation of Schistosoma mansoni-induced infection between immigrants and travellers entering Spain from endemic regions, and to elucidate the therapeutic implications of these infections. A total of 200 African immigrants and 80 travellers with schistosomiasis were included in the study. Among the immigrants, 25 patients were diagnosed with Schistosoma mansoni infection; 15 presented with nonspecific symptoms, and 10 were asymptomatic. Hepatosplenomegaly was observed in nine. Among the travellers, 14 were diagnosed with Schistosoma mansoni infection; four were asymptomatic, four had Katayama syndrome, four had diarrhoea, and two had prostatitis. All of the patients were treated with praziquantel. Patients diagnosed with Katayama syndrome received praziquantel and dexamethasone for 3 days, with the praziquantel treatment being repeated at 3-4 weeks. The significant differences observed in the clinical presentation of Schistosoma mansoni-induced infection, indicate that a well-differentiated therapeutic strategy is required when this infection is diagnosed in a non-immune (traveller) or a semi-immune (immigrant) patient.

Unlabelled: To determine the need of prenatal screening for toxoplasmosis in our hospital from a seroepidemiological point of view., Patients and Methods: The prevalence of IgG anti-T. gondii was retrospectively analyzed in 7.090 women of childbearing age attended in the Hospital Clínic of Barcelona from February 1992 to April 1999. The association among the seroprevalence and the variables year, age, birthplace (province of Barcelona/other provinces) and place of residence (urban/rural) was analyzed. A decreasing trend was observed in the prevalence (p < 0.001), currently being < 40% in the average women between 15 and 45 years. Infection was also directly related to age of women (p < 0.001) and birthplace out of the province of Barcelona (p = 0.001). Habitat (rural or urban) was not associated with seroprevalence. Prenatal screening for toxoplasmosis is necessary due to the high rate of seronegative women exposed to infection and the evidence of a high number of primoinfections in the childbearing period.

Background: To study the usefulness of IgG and IgM titration, and avidity of IgG to date IgM anti-Toxoplasma gondii., Methods: VIDAS Toxo IgG, VIDAS Toxo IgM and VIDAS Toxo IgG Avidity tests were used. 64 sera containing both IgM and IgG T. gondii antibodies were analyzed, 32 from 12 individuals infected 40 weeks previously (group I), and the remainder from 17 individuals with an infection of more than 40 weeks (group II)., Results: An IgM index < 1.05 was associated with an infection > 12 weeks. An avidity index > 0.164 excluded 100% infections of < or = 12 weeks. Avidity indexes > 0.26 and 0.45 excluded infections of < or = 20 and < or = 40 weeks, respectively., Conclusions: The serology methods used in this study can adequately identify residual IgM anti-T. gondii, often avoiding the need of a new blood extraction to analyze IgG kinetics in pregnant women.