Thomas Junghanss

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.

Treatment response of cystic echinococcosis to benzimidazoles: a systematic review.

Over the past 30 years, benzimidazoles have increasingly been used to treat cystic echinococcosis (CE). The efficacy of benzimidazoles, however, remains unclear. We systematically searched MEDLINE, EMBASE, SIGLE, and CCTR to identify studies on benzimidazole treatment outcome. A large heterogeneity of methods in 23 reports precluded a meta-analysis of published results. Specialist centres were contacted to provide individual patient data. We conducted survival analyses for cyst response defined as inactive (CE4 or CE5 by the ultrasound-based World Health Organisation [WHO] classification scheme) or as disappeared. We collected data from 711 treated patients with 1,308 cysts from six centres (five countries). Analysis was restricted to 1,159 liver and peritoneal cysts. Overall, 1–2 y after initiation of benzimidazole treatment 50%–75% of active C1 cysts were classified as inactive/disappeared compared to 30%–55% of CE2 and CE3 cysts. Further in analyzing the rate of inactivation/disappearance with regard to cyst size, 50%–60% of cysts <6 cm responded to treatment after 1–2 y compared to 25%–50% of cysts >6 cm. However, 25% of cysts reverted to active status within 1.5 to 2 y after having initially responded and multiple relapses were observed; after the second and third treatment 60% of cysts relapsed within 2 y. We estimated that 2 y after treatment initiation 40% of cysts are still active or become active again. The overall efficacy of benzimidazoles has been overstated in the past. There is an urgent need for a pragmatic randomised controlled trial that compares standardized benzimidazole therapy on responsive cyst stages with the other treatment modalities.

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.

Cystic echinococcosis: chronic, complex, and still neglected.

The authors have declared that no competing interests exist. n n n nThe Lima workshop was partially funded by the Peruvian National Institute of Health and FIC-NIH training grant TW001140 (to HG). Thomas Junghanss received research funds from NIAID-NIH (grant R34AI091427). HG is now a Wellcome Trust International Senior Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents

Cystic echinococcosis is a worldwide disease caused by larval stages of the parasite Echinococcus granulosus (canine tapeworm). In clinical practice, staging of cyst development by ultrasonography (US) has allowed treatment options to be tailored to individual patient needs. However, the empirical correlation between cyst morphology and parasite viability is not always dependable and has, until now, required confirmation by invasive assessment of cyst content by light microscopy (LM), for example. Alternatively, high‐field 1H MRS may be used to examine cyst fluid ex vivo and prepare detailed quantitative metabolite profiles, enabling a multivariate metabolomics approach to cyst staging. One‐dimensional and two‐dimensional 1H and 1H/13C MRS at 600u2009MHz (14.1u2009T) was used to analyze 50 cyst aspirates of various US and LM classes. MR parameters and concentrations relative to internal valine were determined for 44 metabolites and four substance classes. The high concentrations of succinate, fumarate, malate, acetate, alanine, and lactate found in earlier studies of viable cysts were confirmed, and additional metabolites such as myo‐inositol, sorbitol, 1,5‐anhydro‐D‐glucitol, betaine, and 2‐hydroxyisovalerate were identified. Data analysis and cyst classification were performed using univariate (succinate), bivariate (succinate vs fumarate), and multivariate partial least squares discriminant analysis (PSL‐DA) methods (with up to 48 metabolite variables). Metabolic classification of 23 viable and 18 nonviable cysts on the basis of succinate alone agreed with LM results. However, for seven samples, LM and MRS gave opposing results. Reclassification of these samples and two unclassified samples by PLS‐DA prediction techniques led to a set of 50 samples that could be completely separated into viable and nonviable MRS classes with no overlap, using as few as nine variables: succinate, formate, malate, 2‐hydroxyisovalerate, acetate, total protein content, 1,5‐anhydro‐D‐glucitol, alanine, and betaine. Thus, future noninvasive in vivo applications of MRS would appear promising. Copyright

Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in comparison to ultrasound?

Background Imaging plays the key role in diagnosing and staging of CE. The description of CE-specific imaging features and the WHO CE cyst classification is based on ultrasound. The reproducibility of the ultrasound-defined features of CE cysts is variable in MR- and CT-imaging. This is of particular importance for cysts that are not accessible by US and because of the increasing availability and overuse of CT and MR imaging. Methodology/Principal Findings Retrospective analysis of patients with abdominal CE cysts of an interdisciplinary CE clinic who had CT and/or MRI scans performed additionally to US imaging. All images were read and interpreted by the same senior radiologist experienced in the diagnosis of CE. US, CT and MR images were staged according to the WHO classification criteria. The agreement beyond chance was quantified by kappa coefficients (κ). 107 patients with 187 CE cysts met the inclusion criteria. All cysts were assessed by US, 138 by CT, and 125 by MRI. The level of agreement beyond chance of the individual CE stages 1–4 was clearly lower for CT, with κ ranging from 0.62 to 0.72, compared to MRI with values of κ between 0.83 and 1.0. For CE5 cysts CT (κu200a=u200a0.95) performed better than MRI (κu200a=u200a0.65). Conclusions Ultrasound remains the corner stone of diagnosis, staging and follow up of CE cysts. MRI reproduces the ultrasound-defined features of CE better than CT. If US cannot be performed due to cyst location or patient-specific reasons MRI with heavily T2-weighted series is preferable to CT.

Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

BackgroundThe overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19th Century. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment.MethodsA prospective study of confirmed culture positive cases of pulmonary TB and their contacts was carried out in a German federal state from 2003 to 2005. Data for the study included: 1) case data routinely collected by the local public health staff and transmitted to the state health office and the national surveillance centre, 2) a study questionnaire designed to capture social interactions of relevance for TB transmission and 3) molecular genotyping data (IS6110 DNA fingerprint and spoligotyping). The proportion of German cases caused by foreign-born cases, and vice versa, was estimated and an integration index was computed using a selected set of questions from the study questionnaire.ResultsA total of 749 cases of culture-positive pulmonary tuberculosis voluntarily enrolled in the study, representing 57.8% of all registered cases diagnosed over the study period. Data that included study questionnaire and DNA fingerprinting were available for 41% (n = 308) of the study participants. Forty-seven clusters, defined as a least two cases infected by the same TB strains, were identified by molecular methods and included 132 (17%) of the study participants. Epidemiological links were identified for 28% of the clusters by conventional epidemiological data. In mixed clusters, defined as clusters including German and foreign-born individuals, the probability of cases to be caused by foreign-born cases was estimated at 18.3%. We observed a trend to mixed clusters with increasing time spent by immigrants in the host country. This group also presented comparatively higher integration indexes than immigrants in immigrant-only clusters.ConclusionOur results confirm the findings of other studies that there is no significant TB transmission from TB high-prevalence immigrant to TB low-prevalence autochthonous population. This may be explained by the good performance of tuberculosis screening programmes for certain groups arriving in Germany from high- prevalence countries, by a low degree of mixing of immigrants with the local population or by a combination of both.

Serologic Vaccination Response after Solid Organ Transplantation: A Systematic Review

Background Infectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting. Methods In this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella. Results Of the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly. Conclusion Vaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts.

Medically Important Venomous Animals: Biology, Prevention, First Aid, and Clinical Management

Venomous animals are a significant health problem for rural populations in many parts of the world. Given the current level of the international mobility of individuals and the inquisitiveness of travelers, clinicians and travel clinics need to be able to give advice on the prevention, first aid, and clinical management of envenoming. Health professionals often feel overwhelmed by the taxonomy of venomous animals; however, venomous animals can be grouped, using a simple set of criteria, into cnidarians, venomous fish, sea snakes, scorpions, spiders, hymenoterans, and venomous terrestrial snakes. Geographic distribution, habitats, and circumstances of accidents further reduce the range of culprits that need to be considered in any single event. Clinical management of envenomed patients relies on supportive therapy and, if available, specific antivenoms. Supplies of life-saving antivenoms are scarce, and this scarcity particularly affects rural populations in resource-poor settings. Travel clinics and hospitals in highly industrialized areas predominantly see patients with injuries caused by accidents involving marine animals: in particular, stings by venomous fish and skin damage caused by jellyfish. However, globally, terrestrial venomous snakes are the most important group of venomous animals.

Contiguous spread of Mycobacterium ulcerans in Buruli ulcer lesions analysed by histopathology and real-time PCR quantification of mycobacterial DNA

The distribution of M. ulcerans in Buruli ulcer lesions was analysed by IS2404 real‐time PCR quantification of M. ulcerans DNA and by semi‐quantitative microscopic assessment of the number of acid‐fast bacilli (AFB). Mycobacterial burden was compared with histopathological changes. Focal distribution of tissue destruction extending into areas with high and low mycobacterial burden was a feature in all lesions analysed. Even where most of the mycobacteria were washed out of ulcerative lesions, peaks of mycobacterial DNA and AFB in the necrotic base of the ulcers still marked the position of the primary infection focus. Significant amounts of mycobacterial DNA and microcolonies were also present in samples from more peripheral regions and occasionally in excised margins of macroscopically and histologically healthy‐appearing excised tissue margins. Additional peaks of mycobacterial DNA clearly marked sites where satellite lesions were developing. Even when granulomas provided evidence for the development of cell‐mediated immunity, development of satellite lesions by contiguous spreading was not completely prevented. Areas free of mycobacterial DNA were found between primary and secondary infection foci and around scarring tissue of healing lesions. These results demonstrate that IS2404 real‐time PCR analysis is a better tool than the less sensitive and only semi‐quantitative microscopic enumeration of AFB for studying the dynamics of M. ulcerans infection in situ. Copyright