Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

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.

Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement.

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.

Executive summary consensus statement of imported diseases group (GEPI) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SETMSI), on the diagnostic and treatment of imported schistosomiasis.

Schistosomiasis is a highly prevalent disease, especially in immigrant populations, and is associated with significant morbidity and diagnostic delays outside endemic areas. For these reasons, the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SEMTSI) have developed a joint consensus document to serve as a guide for the screening, diagnosis and treatment of this disease outside endemic areas. A panel of experts from both societies identified the main questions to be answered and developed recommendations based on the scientific evidence available at the time. The document was reviewed by the members from both societies for final approval.

[Screening for strongyloidiasis in Spain in the context of the SARS-CoV-2 pandemic: Results of a survey on diagnosis and treatment]. / Cribado de estrongiloidiosis en España en el contexto de la pandemia SARS-CoV-2: resultados de una encuesta sobre diagnóstico y tratamiento.

Introduction: The generalization of treatment with dexamethasone or other immunosuppressants in patients with SARS-CoV-2 infection may increase the risk of occurrence of severe forms of strongyloidiasis. A nationwide survey was conducted to better understand the diagnostic and therapeutic situation of strongyloidiasis in SARS-CoV-2 co-infected patients in Spain. Materials and methods: A survey was designed and sent to all SEIMC members during February and March 2021. Responses were exported for computer processing to Microsoft Excel 2017 and statistically processed with the free software PSPP. Results: 189 responses were received, of which 121 (64%) were selected for further processing. Eighty-four centers (69.5%) had no specific strongyloidiasis screening protocol. Forty-two centers (34.7%) had serological techniques available in their laboratories and the rest were sent to a reference laboratory. Only 22 centers (18%) screened for strongyloidiasis in SARS-CoV-2 infected patients. A total of 227 cases of strongyloidiasis were diagnosed in patients with SARS-CoV-2 infection. In four cases patients developed a massive hyperinfestation syndrome leading to the death of one patient. Conclusion: COVID-19 has highlighted the need to unify screening and treatment protocols for imported pathologies such as strongyloidiasis. Efforts to disseminate knowledge are needed to ensure that this potentially fatal disease is adequately treated in patients with the highest risk of complications, such as those with COVID-19.

Screening for strongyloidiasis in Spain in the context of the SARS-CoV-2 pandemic: Results of a survey on diagnosis and treatment.

INTRODUCTION: The generalization of treatment with dexamethasone or other immunosuppressants in patients with SARS-CoV-2 infection may increase the risk of occurrence of severe forms of strongyloidiasis. A nationwide survey was conducted to better understand the diagnostic and therapeutic situation of strongyloidiasis in SARS-CoV-2 co-infected patients in Spain. MATERIALS AND METHODS: A survey was designed and sent to all SEIMC members during February and March 2021. Responses were exported for computer processing to Microsoft Excel 2017 and statistically processed with the free software PSPP. RESULTS: 189 responses were received, of which 121 (64%) were selected for further processing. Eighty-four centers (69.5%) had no specific strongyloidiasis screening protocol. Forty-two centers (34.7%) had serological techniques available in their laboratories and the rest were sent to a reference laboratory. Only 22 centers (18%) screened for strongyloidiasis in SARS-CoV-2 infected patients. A total of 227 cases of strongyloidiasis were diagnosed in patients with SARS-CoV-2 infection. In four cases patients developed a massive hyperinfestation syndrome leading to the death of one patient. CONCLUSION: COVID-19 has highlighted the need to unify screening and treatment protocols for imported pathologies such as strongyloidiosis. Efforts to disseminate knowledge are needed to ensure that this potentially fatal disease is adequately treated in patients with the highest risk of complications, such as those with COVID-19.

Chagas disease in the United Kingdom: A review of cases at the Hospital for Tropical Diseases London 1995-2018. The current state of detection of Chagas disease in the UK.

BACKGROUND: Chagas disease (CD), is a parasitic disease endemic in Latin America. Presentation in non-endemic areas is either in the asymptomatic indeterminate phase or the chronic phase with cardiac and/or gastrointestinal complications. METHODS: The Hospital for Tropical Diseases (HTD) based in central London, provides tertiary care for the management of CD. We reviewed all cases managed at this centre between 1995 and 2018. RESULTS: Sixty patients with serologically proven CD were identified. Most were female (70%), with a median age at diagnosis of 41 years. Three quarters of the patients were originally from Bolivia. 62% of all patients were referred to the HTD by their GP. Nearly half of the patients were asymptomatic (47%). Twelve patients had signs of cardiac involvement secondary to CD. Evidence of gastrointestinal damage was established in three patients. Treatment was provided at HTD for 31 patients (47%). Most patients (29) received benznidazole, five of them did not tolerate the course and were switched to nifurtimox. Of the seven patients receiving this second line drug, five completed treatment, whilst two interrupted it due to side effects. CONCLUSIONS: Despite the UK health system having all the resources required to diagnose, treat and follow up cases, there is lack of awareness of CD, such that the vast majority of cases remain undiagnosed and therefore do not receive treatment. We propose key interventions to improve the detection and management of this condition in the UK, especially in pregnant women and neonates.

Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers.

The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.

Acute liver failure due to visceral leishmaniasis in Barcelona: a case report.

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.

Pneumocystis pneumonia in the twenty-first century: HIV-infected versus HIV-uninfected patients.

Introduction: Pneumocystis pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging number of conditions associated with immunosuppression has led to its appearance in other patient populations. Areas covered: This article reviews the most recent publications on PcP in the HIV-infected and HIV-uninfected population, focusing on epidemiology, diagnostic, therapy and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles including randomized clinical trials, meta-analyses, observational studies and clinical reviews. Expert opinion: The growing incidence of Pneumocystis infection in the HIV-uninfected population suggests the need for new global epidemiological studies in order to identify the true scale of the disease in this population. These data would allow us to improve diagnosis, therapeutic strategies, and clinical management. It is very important that both patients and physicians realize that HIV-uninfected patients are at risk of PcP and that rapid diagnosis and early initiation of treatment are associated with better prognosis. Currently, in-hospital mortality rates are very high: 15% for HIV-infected patients and 50% in some HIV-uninfected patients. Therefore, adequate preventive measures should be implemented to avoid the high mortality rates seen in recent decades.

Unmasking the hidden tuberculosis mortality burden in a large post mortem study in Maputo Central Hospital, Mozambique.

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.

Emergence of Resistance to Quinolones and ß-Lactam Antibiotics in Enteroaggregative and Enterotoxigenic Escherichia coli Causing Traveler's Diarrhea.

The objective of this study was to assess the antimicrobial resistance of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) strains causing traveler's diarrhea (TD) and to investigate the molecular characterization of antimicrobial resistance genes to third-generation cephalosporins, cephamycins, and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibilities of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin, azithromycin, and rifaximin were determined. All genes encoding resistance determinants were detected by PCR or PCR plus DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using multilocus sequence typing (MLST). The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages have been found especially in patients traveling to India and sub-Saharan Africa. Sequence type 38 (ST38) and ST131, carrying the blaCTX-M-15 and blaCTX-M-27 genes, respectively, are highly prevalent among extended-spectrum ß-lactamase (ESBL)-producing EAEC and ETEC strains. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to Southeast Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC, with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.

Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients.

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.

Severe Babesia microti infection in an American immunocompetent patient diagnosed in Spain.

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.

Aetiology, epidemiology and clinical characteristics of acute moderate-to-severe diarrhoea in children under 5 years of age hospitalized in a referral paediatric hospital in Rabat, Morocco.

The objective of the study was to describe the aetiology, epidemiology and clinical characteristics of the principal causes of acute infectious diarrhoea requiring hospitalization among children under 5 years of age in Rabat, Morocco. A prospective study was conducted from March 2011 to March 2012, designed to describe the main pathogens causing diarrhoea in hospitalized children >2 months and less than 5 years of age. Among the 122 children included in the study, enteroaggregative Escherichia coli (EAEC) and rotavirus were the main aetiological causes of diarrhoea detected. Twelve (9.8 %) children were referred to an intensive care unit, while two, presenting infection by EAEC, and EAEC plus Shigella sonnei, developed a haemolytic uraemic syndrome. Additionally, six (4.9 %) deaths occurred, with EAEC being isolated in four of these cases. Diarrhoeagenic E. coli and rotavirus play a significant role as the two main causes of severe diarrhoea, while other pathogens, such as norovirus and parasites, seem to have a minimal contribution. Surveillance and prevention programmes to facilitate early recognition and improved management of potentially life-threatening diarrhoea episodes are needed.

Protease inhibitor monotherapy is associated with a higher level of monocyte activation, bacterial translocation and inflammation.

INTRODUCTION: Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. METHODS: We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed. RESULTS: CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16-CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16-CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01). CONCLUSIONS: Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.