Pulmonary cystic echinococcosis.

PURPOSE OF REVIEW: The aim of our review is to summarize specific clinical, diagnostic and treatment aspects of pulmonary cystic echinococcosis. The lung is the organ second most affected by cystic echinococcosis with approximately a quarter of cystic echinococcosis cysts. Most cysts are in the liver. Apart from the watch and wait approach for selected inactive cysts [cystic echinococcosis CE4, CE5], the well established WHO cystic echinococcosis cyst classification-based treatment of hepatic cystic echinococcosis cannot be applied to pulmonary cystic echinococcosis cysts. Some standard interventions can even be harmful when applied to pulmonary cystic echinococcosis cysts. RECENT FINDINGS: Cystic echinococcosis is one of the neglected tropical diseases (NTDs). Development of new diagnostics and treatment modalities is hampered by low investment into research and is accordingly slow. SUMMARY: Surgery is the mainstay of treatment for pulmonary cystic echinococcosis cysts. Parenchyma-sparing surgical techniques should be used whenever possible. Albendazole induces decay of the parasitic cyst membrane, opening of cystobronchial fistulas and cyst complications, which can be life threatening. It is strongly recommended to seek advice from expert centres, including differential diagnoses, treatment and a long-term management plan.

Disseminated Mycosis by Arthrocladium fulminans Jeopardizing a Patient with GATA2 Deficiency.

GATA2 deficiency is characterized by monocytopenia, deficiency of dendritic cells, and a variable degree of lymphocytopenia affecting B cells and NK cells, leading to an enhanced risk of mycobacterial, viral, and fungal infections. Here we present a patient with a heterozygous intronic GATA2 mutation who acquired a fatal disseminated mycosis due to the black yeast-like fungus Arthrocladium fulminans following an infection with Mycobacterium sherrisii. This case illustrates that in patients with severe uncommon infections, immunodeficiency syndromes must be ruled out.

Clinical management of cystic echinococcosis: state of the art and perspectives.

PURPOSE OF REVIEW: This review draws attention to patients with cystic echinococcosis migrating from highly endemic to non-endemic countries with limited experience in cystic echinococcosis management, to ultrasound-based cyst staging, and to the WHO cyst classification as a powerful, to date underused tool to triage patients into the four currently available treatment modalities. RECENT FINDINGS: In non- and low-prevalence countries, cystic echinococcosis is often misclassified. Differential diagnoses, such as simple cysts and other benign and malignant space-occupying lesions, have similar appearances on imaging. Serology is confirmatory but often disappointing due to sensitivity and specificity problems. There is increasing confidence in assigning uncomplicated cystic echinococcosis cysts to the four treatment modalities [drug treatment (benzimidazoles), percutaneous methods, surgery, watch and wait] on the basis of cyst stage (WHO cyst classification), size and location. However, current best practice is still not widely implemented outside cystic echinococcosis treatment centres, and further consolidation is needed by well-designed clinical trials. Recently published long-term follow-up studies have shown that patients with inactive cyst stages CE4 and CE5 benefit, especially since they do not need any treatment at all if they have not received prior benzimidazole or percutaneous therapy. Instead, cysts that have reached cyst stages CE4 and CE5 through drug treatment do need careful follow-up as they often relapse. Surgical procedures in which the cysts are opened and percutaneous approaches require very careful control of cyst content spillage to the peritoneum, pleura and intravascularly to prevent dissemination - a still too often neglected issue with severe consequences for patients. SUMMARY: Though a neglected disease with predominantly expert-opinion-based treatment strategies, cystic echinococcosis patients can greatly benefit from interdisciplinary management in cystic echinococcosis treatment centres and cyst-stage-based assignment of treatment modalities. Increased suspicion for cystic echinococcosis in migrants from endemic to non-endemic countries is urgently needed at the current level of global mobility.

Performance of Magnetic Resonance Susceptibility-Weighted Imaging for Detection of Calcifications in Patients With Hepatic Echinococcosis.

OBJECTIVE: We evaluated the performance of susceptibility-weighted imaging (SWI) for identification of hepatic calcifications in alveolar echinococcosis and cystic echinococcosis. METHODS: The SWI images of 58 lesions in 40 patients (age, 49 ± 14 y) with alveolar echinococcosis (n = 22) or cystic echinococcosis (n = 18) were reviewed for calcifications. First, calcifications were suggested by visual assessment. Second, ratios of minimum intralesional intensity and mean lumbar muscle intensity were recorded. Computed tomography (CT) served as the criterion standard. RESULTS: Thirty-seven lesions showed calcifications on CT. Susceptibility-weighted imaging provided a sensitivity of 89.2% (95% confidence interval [CI], 50.1-75.7) and a specificity of 57.1% (95% CI, 34.4-77.4) for calcifications detected by visual assessment. Receiver operating characteristic curves demonstrated a sensitivity of 67.6% and a specificity of 85.0% for an intensity ratio of 0.61. A specificity of 100% (95% CI, 80.8-100) and a sensitivity of 84.5% (95% CI, 67.3-93.2) were achieved by SWI for calcifications with a density greater than 184 HU in CT. CONCLUSIONS: Identification of hepatic calcifications is possible with SWI. Susceptibility-weighted imaging offers the potential to reduce the need for of CT imaging for evaluation of echinococcosis.

Follow-up of surgically treated patients with cystic echinococcosis: can novel recombinant antigens compete with imaging? Analysis of a patient cohort.

OBJECTIVE: To compare the performance of two novel recombinant antigens (EgP29, 2B2t) with imaging in a well-defined cohort of surgically treated cystic echinococcosis (CE) patients to determine whether serology reflects surgical cure as defined by imaging. METHODS: From a cohort of 223 CE-confirmed patients of a national clinical center for echinococcosis, 36 surgically treated patients were eligible for analysis. Sera were tested by enzyme-linked immunosorbent assay (ELISA) for specific IgG and IgG4 antibodies against the EgP29 and 2B2t antigens. We used a hierarchical linear regression model to examine the course of antibody levels over time for each patient. A meta-analysis of the patient-specific estimates of the time to negativity was performed using the metan command in Stata. RESULTS: The range of positive serological results at the beginning of post-surgical monitoring was 34-60%: 2B2t 51%, 2B2t-IgG4 34%, EgP29 60% and EgP29-IgG4 40%. The pooled estimates of time to seronegativity were as follows: 2B2t-ELISA 3.92 (3.24, 4.61) years; 2B2t-IgG4-ELISA 4.60 (3.91, 5.29) years; EgP29-ELISA 3.94 (3.50, 4.39) years; EgP29-IgG4-ELISA 2.55 (1.93, 3.18) years. CONCLUSION: After surgical treatment, antibodies to the recombinant antigens 2B2t and EgP29 become negative in the majority of CE-confirmed, surgically cured patients. The major drawback is the fact that only around half of the CE-confirmed, surgically treated patients were at all responsive to the test antigens, so they are of limited benefit for documenting primary cure. Equally, these antigens do not appear to be sensitive to recurrences.

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND: Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS: In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS: Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS: Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION: ISRCT 72102977.

Vascular leakage in dengue--clinical spectrum and influence of parenteral fluid therapy.

OBJECTIVE: Clinical management of dengue relies on careful monitoring of fluid balance combined with judicious intravenous (IV) fluid therapy. However, in patients with significant vascular leakage, IV fluids may aggravate serosal fluid accumulation and result in respiratory distress. METHODS: Trained physicians followed suspected dengue cases prospectively at seven hospitals across Asia and Latin America, using a comprehensive case report form that included daily clinical assessment and detailed documentation of parenteral fluid therapy. Applying Cox regression, we evaluated risk factors for the development of shock or respiratory distress with fluid accumulation. RESULTS: Most confirmed dengue patients (1524/1734, 88%) never experienced dengue shock syndrome (DSS). Among those with DSS, 176/210 (84%) had fluid accumulation, and in the majority (83%), this was detectable clinically. Among all cases with clinically detectable fluid accumulation, 179/447 (40%) were diagnosed with shock or respiratory distress. The risk for respiratory distress with fluid accumulation increased significantly as the infused volume over the preceding 24 h increased (hazard ratio 1.18 per 10 ml/kg increase; P < 0.001). Longer duration of IV therapy, use of a fluid bolus in the preceding 24 h, female gender and poor nutrition also constituted independent risk factors. CONCLUSIONS: Shock and respiratory distress are relatively rare manifestations of dengue, but some evidence of fluid accumulation is seen in around 50% of cases. IV fluids play a crucial role in management, but they must be administered with caution. Clinically and/or radiologically detectable fluid accumulations have potential as intermediate severity endpoints for therapeutic intervention trials and/or pathogenesis studies.

Dengue expansion in Africa-not recognized or not happening?

An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services.

The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis.

BACKGROUND: The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9). METHODS: CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. RESULTS: Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-γ , MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-α, IL-1 ß, IL-1RA, IL-6, and TGF-α were significantly higher. CONCLUSION: The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae.

Vascular pathology in patients with alveolar echinococcosis: framework for assessment and clinical management - a retrospective case series.

OBJECTIVE: Alveolar echinococcosis (AE) is a parasitic liver disease with infiltrative growth similar to solid organ malignancies. Major vascular damage is frequent and often remains untreated until catastrophic events precipitate. Detailed clinical and radiological assessment is required to guide individualised treatment decisions. Standardised radiological reporting templates of malignancies with profiles resembling AE are candidates for adaptation. Our objectives are to describe vascular pathology in AE and establish a framework for structured evaluation as the basis for treatment decisions and monitoring. DESIGN: Retrospective case series. RESULTS: 69 patients (37.1%) had vascular involvement: portal vein (PV) 24.7%, hepatic vein (HV) 22.6% inferior vena cava (IVC) 13.4%. Significant stenosis/occlusion of vessels was present in 15.1% of PV, in 13.4% of HV and in 7.5% of IVC involvement. Vascular pathology needing specific treatment or monitoring was present in 8.6% of patients. The most frequent clinical presentation was high grade IVC stenosis or occlusion which was seen in 11 patients of the cohort. CONCLUSION: Advanced AE requires early multidisciplinary assessment to prevent progressive impairment of liver function due to vascular damage. The focus at first presentation is on complete evaluation of vascular (and biliary) involvement. The focus in non-resectable AE is on prevention of vascular (and biliary) complications while suppressing growth of AE lesions by benzimidazole treatment to improve the quality of life of patients. We developed a framework for standardised vascular assessment and follow-up of patients with AE to recognise and treat complications early.

Maternofetal consequences of Coxiella burnetii infection in pregnancy: a case series of two outbreaks.

BACKGROUND: A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of Coxiella burnetii infection contracted during pregnancy. METHODS: Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture. RESULTS: 11 pregnant women from Soest (screening rate: 49%) and 82 pregnant women from Jena (screening rate: 27%) participated in the outbreak investigation. 11 pregnant women with an acute C. burnetii infection were diagnosed. Three women had symptomatic disease. Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3), were treated with macrolides for three weeks (n=1) or after delivery (n=1), were given no treatment at all (n=2) or received antibiotics ineffective for Q fever (n=1). One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35th week) and one child was born with syndactyly. We found no obvious association between C. burnetii infection and negative pregnancy outcome. CONCLUSIONS: Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic C. burnetii infections and with chronic Q fever should be treated. The risk-benefit ratio of treatment in these patients, however, remains uncertain. If cotrimoxazole is administered, folinic acid has to be added.

Skin wounds in a rural setting of Côte d'Ivoire: Population-based assessment of the burden and clinical epidemiology.

BACKGROUND: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. METHODS: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. RESULTS: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. CONCLUSIONS: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. TRIAL REGISTRATION: Registration at ClinicalTrials.gov NCT03957447.

Community-based wound management in a rural setting of Côte d'Ivoire.

BACKGROUND: Wounds are a neglected health problem in rural communities of low-income countries, mostly caused by trauma and ulcerative skin diseases including Neglected Tropical Diseases (NTDs) and associated with systemic complications and disability. Rural communities have limited access to high quality health services-based wound care. METHODS: We conducted a prospective observational study on wound management at three levels-community (C), health centre (HC), district hospital (DH)-in a rural community of Côte d'Ivoire. Patients with skin wounds actively identified in a house-to-house survey and passively in the health services in a defined area of the Taabo Health and Demographic Surveillance System were asked to participate and followed-up longitudinally. Endpoints were proportion of wounds closed, time to wound closure, wound size over time, frequency of secondary bacterial infection, need for recapturing after follow-up interruption, and duration of treatment stratified by health service level and wound aetiology. RESULTS: We enrolled 561 patients with 923 wounds between May 2019 and March 2020. The observation period ended in March 2021. Median age was 10 years (IQR 7-15), 63.0% of patients were male. Almost all (99.5%, 870/874) wounds closed within the observation period, 5.3% (49/923) were lost to follow-up. Wounds primarily treated in C, HC and DH closed within a median time of 10, 16 and 170 days, respectively. Median time to acute wound and chronic wound closure was 13 and 72 days, respectively. Wounds treated in C, HC and DH presented with secondary bacterial infections in 10.3% (36/350), 31.0% (133/429) and 100% (5/5) of cases, respectively. Recapturing was required in 68.3% (630/923) of wounds with participants reporting wound closure as the main reason for not attending follow-up. CONCLUSIONS: We describe a wound management model based on national and WHO recommendations focusing on early identification and treatment in the community with potential for broad implementation in low-income countries. TRIAL REGISTRATION: Registration at ClinicalTrials.gov (NCT03957447).

Intravenous artesunate for severe malaria in travelers, Europe.

Multicenter trials in Southeast Asia have shown better survival rates among patients with severe malaria, particularly those with high parasitemia levels, treated with intravenous (IV) artesunate than among those treated with quinine. In Europe, quinine is still the primary treatment for severe malaria. We conducted a retrospective analysis for 25 travelers with severe malaria who returned from malaria-endemic regions and were treated at 7 centers in Europe. All patients survived. Treatment with IV artesunate rapidly reduced parasitemia levels. In 6 patients at 5 treatment centers, a self-limiting episode of unexplained hemolysis occurred after reduction of parasitemia levels. Five patients required a blood transfusion. Patients with posttreatment hemolysis had received higher doses of IV artesunate than patients without hemolysis. IV artesunate was an effective alternative to quinine for treatment of malaria patients in Europe. Patients should be monitored for signs of hemolysis, especially after parasitologic cure.

Salmonella enterica serovar Virchow bacteremia presenting as typhoid-like illness in an immunocompetent patient.

We report a typhoid-like illness with fever and altered consciousness in a 22-year-old man with growth of Salmonella enterica serovar Virchow in blood and stool culture. Bacteremia and invasive disease due to non-typhoid salmonellae (NTS) are known in severely immunocompromised patients, but so far have not been described in immunocompetent adults.

Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients.

Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.

Update on cystic hydatid disease.

PURPOSE OF REVIEW: Cystic echinococcosis, or cystic hydatidosis, is a complex, chronic disease with a cosmopolitan distribution. In humans, its clinical spectrum ranges from asymptomatic infection to severe, rarely even fatal disease. Four approaches in clinical management exist: surgery, percutaneous techniques and drug treatment for active cysts, and the so-called watch and wait approach for inactive cysts. Allocation of patients to these treatments should be based on cyst stage, size and location, available clinical expertise and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated.We review the currently available evidence for clinical decision-making and discuss ways to improve standards of care of one of the most neglected infectious diseases. RECENT FINDINGS: Data are mostly derived from case series and small clinical trials, and treatment guidelines remain at the level of expert opinion. No single high-quality comparative clinical trial of the four treatment options is available to resolve important questions such as stage-specific allocation of treatments, adverse events and long-term relapse rates. Recent work is beginning to acknowledge this problem. SUMMARY: Currently, four treatment modalities are available for cystic echinococcosis. The level of evidence on which clinicians have to rely is low. For the time being patients should thus be treated in referral centres. Proper comparative clinical trials are urgently needed.

Invasive Aspergillus fumigatus infection after Plasmodium falciparum malaria in an immuno-competent host: case report and review of literature.

Invasive fungal infection is rarely reported in association with malaria, even though malaria-associated inhibition of phagocyte function is a well-known condition. Invasive aspergillosis is frequently found in severely immuno-compromised patients but not in healthy individuals. Here, a case of pulmonary invasive aspergillosis in a previously healthy patient with severe P. falciparum malaria is presented, who was successfully treated with voriconazol and caspofungin. This is the first survival of malaria-associated invasive aspergillosis.