Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

INTRODUCTION: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB. METHODS AND ANALYSIS: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study. ETHICS AND DISSEMINATION: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL8347 (the Netherlands Trial Register).

[An unvaccinated man with a painful arm and jaw]. / Een ongevaccineerde man met een pijnlijke arm en kaak.

BACKGROUND: Clostridium tetani is a gram-positive spore-forming bacterium that produces toxins and grows under anaerobic conditions. Infections with this bacterium can lead to local or generalised forms of tetanus. CASE DESCRIPTION: An 83-year-old man presented to the acute cardiac care unit with a painful left arm and jaw. Because the patient had a hypertonic left arm and was unable to open his mouth fully, the neurologist was consulted. The patient had been to the emergency department 9 days earlier for an infected wound after falling in the garden. He had not been actively or passively immunised against tetanus at that time. On inquiry, it appeared that the patient had also not been vaccinated as a child. We made a clinical diagnosis of tetanus. The patient was admitted and treated with tetanus immunoglobulin, metronidazole, diazepam and painkillers. He was also administered tetanus toxoid and the wound was cleaned. After 1 month and 7 months, the patient was again administered tetanus toxoid. CONCLUSION: Patients with a wound that may have come into contact with road grime, dirt or manure, should always be asked for their vaccination status, especially people from high-risk groups, such as the elderly.

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial.

OBJECTIVES: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. METHODS: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. RESULTS: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). CONCLUSIONS: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.

The burden of depression and anxiety among medical students in South Africa: A cross-sectional survey at the University of Cape Town.

BACKGROUND: Depressive and anxiety disorders occur at very high rates among medical students. For instance, an international review and meta-analysis estimated the overall pooled crude prevalence of depression or depressive symptoms at 27.2%. However, South African (SA) data are very limited. OBJECTIVES: To determine rates of depression and anxiety among medical students and to examine the associations with various sociodemographic variables (biological sex, gender identity, household income, ethnicity, and clinical v. pre-clinical students). We also examined whether the 'mini-semester' of 2017 resulting from the 2016 'Fees Must Fall' student protests was associated with increased depression/anxiety. METHODS: The study was a cross-sectional electronic survey conducted in the Faculty of Health Sciences, University of Cape Town, using an anonymous, self-administered online questionnaire. The questionnaire included basic sociodemographic questions, the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale. RESULTS: The sample consisted of 473 medical students, 333 (70.4%) female and 140 (29.6%) male. Based on ethnic self-identification, 165 (35.6%) were black, 144 (31.1%) white, 88 (19%) coloured, 52 (11.2%) Indian and 8 (1.7%) Asian. There were 239 pre-clinical students (50.5%) and 234 clinical students (49.5%). Of the sample, 36.4% were above the cut-off for major depressive disorder and 45.9% for anxiety disorder. Reported rates of disorders diagnosed by a health professional were 25.0% for depressive disorder and 20.5% for anxiety disorder, and 28.1% of all students were receiving psychotropic medication. Female sex was associated with both depression (prevalence ratio (PR) 3.7; p<0.001) and anxiety diagnoses (PR 4.7; p<0.001). None of the other sociodemographic characteristics showed significant associations. Interestingly, students who undertook the 2017 mini-semester showed an increased rate of depression (PR 2.1; p<0.05) and anxiety diagnoses (PR 2.1; p<0.05). CONCLUSIONS: Nearly one in four students reported depression/anxiety diagnoses and were on psychotropic medication, significantly more than age-based expectations. Even more screened positive for risk of depression/anxiety. Our findings indicate that medical students, particularly females, are at a significantly increased risk of depression and anxiety disorders. Results suggest that the 2016 student protests may have had a direct impact on the mental state of students. Multidisciplinary efforts should be targeted at initiatives to strengthen mental wellbeing and institutional culture around mental health. These efforts may help build resilience in the next generation of health professionals in SA ahead of work in an overburdened health and health education system.

Correction to: Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia.

The article "Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia", written by K. Bolhuis, L. J. Bakker, J. T. Keijer, and P. J. de Vries was originally published electronically on 31 May 2018 with incorrect copyright line in the publisher's internet portal.

Recurrence quantification analysis of resting state EEG signals in autism spectrum disorder - a systematic methodological exploration of technical and demographic confounders in the search for biomarkers.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a worldwide prevalence of 1-2%. In low-resource environments, in particular, early identification and diagnosis is a significant challenge. Therefore, there is a great demand for 'language-free, culturally fair' low-cost screening tools for ASD that do not require highly trained professionals. Electroencephalography (EEG) has seen growing interest as an investigational tool for biomarker development in ASD and neurodevelopmental disorders. One of the key challenges is the identification of appropriate multivariate, next-generation analytical methodologies that can characterise the complex, nonlinear dynamics of neural networks in the brain, mindful of technical and demographic confounders that may influence biomarker findings. The aim of this study was to evaluate the robustness of recurrence quantification analysis (RQA) as a potential biomarker for ASD using a systematic methodological exploration of a range of potential technical and demographic confounders. METHODS: RQA feature extraction was performed on continuous 5-second segments of resting state EEG (rsEEG) data and linear and nonlinear classifiers were tested. Data analysis progressed from a full sample of 16 ASD and 46 typically developing (TD) individuals (age 0-18 years, 4802 EEG segments), to a subsample of 16 ASD and 19 TD children (age 0-6 years, 1874 segments), to an age-matched sample of 7 ASD and 7 TD children (age 2-6 years, 666 segments) to prevent sample bias and to avoid misinterpretation of the classification results attributable to technical and demographic confounders. A clinical scenario of diagnosing an unseen subject was simulated using a leave-one-subject-out classification approach. RESULTS: In the age-matched sample, leave-one-subject-out classification with a nonlinear support vector machine classifier showed 92.9% accuracy, 100% sensitivity and 85.7% specificity in differentiating ASD from TD. Age, sex, intellectual ability and the number of training and test segments per group were identified as possible demographic and technical confounders. Consistent repeatability, i.e. the correct identification of all segments per subject, was found to be a challenge. CONCLUSIONS: RQA of rsEEG was an accurate classifier of ASD in an age-matched sample, suggesting the potential of this approach for global screening in ASD. However, this study also showed experimentally how a range of technical challenges and demographic confounders can skew results, and highlights the importance of probing for these in future studies. We recommend validation of this methodology in a large and well-matched sample of infants and children, preferably in a low- and middle-income setting.

Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia.

Staphylococcus aureus bacteraemia (SAB) is associated with high-mortality and complication rates. A multidisciplinary approach is needed to predict, detect and treat complications. In this pre- and post-intervention study, we investigated the effects of a hospital-wide protocol for diagnosis, classification and treatment of SAB. It was hypothesized that complications and endocarditis would be better identified and treated. Medical records of SAB patients admitted in 2011 and 2012 (pre) were analysed. In 2013, a protocol, describing risk factors, diagnostic classification and recommended treatment, was implemented. In 2014 and 2015 (post), SAB patients were followed prospectively. Transthoracic (TTE) or transoesophageal cardiac ultrasound (TEE) was chosen following a decision tree. A resident internal medicine acted as contact person. Pre-intervention, 98 patients were eligible for analysis compared to 85 patients post-intervention. Age and number of risk factors were slightly higher post-intervention; other baseline characteristics were similar. Most SAB-patients were classified as complicated (89 and 82% pre- and post-intervention, respectively). Follow-up blood cultures drawn within 2 days after initiating treatment increased from 51 to 85%. Cardiac ultrasounds increased from 44 to 83% for TTE and 13 to 24% for TEE. Endocarditis was more frequently diagnosed (4 vs. 12%). Additionally, duration of antibiotic therapy increased. The 3-month mortality did not change significantly (33% pre-intervention vs. 35% post-intervention; p > 0.05). Introduction of a hospital-wide protocol for SAB management increased standard of care, created awareness among clinicians to properly classify SAB, search for endocarditis and adapt duration of antibiotic treatment. Mortality did not decrease.

An unusual causative pathogen of sepsis after a cat bite: Anaerobiospirillum succiniciproducens.

A 40-year-old woman with a history of liver cirrhosis presented with septic shock caused by an Anaerobiospirillum succiniciproducens bacteraemia after a cat bite. A. succiniciproducens sepsis can develop after a cat or dog bite, especially in immunocompromised hosts, or might occur after translocation from the gut flora. It is a potentially lethal infection.

Effect of everolimus on skin lesions in patients treated for subependymal giant cell astrocytoma and renal angiomyolipoma: final 4-year results from the randomized EXIST-1 and EXIST-2 studies.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder associated with tumour growth in various organs, including the brain, kidneys, heart and skin. Cutaneous lesions are prevalent manifestations of TSC, occurring in up to 90% of patients. Oral mammalian target of rapamycin inhibitors, such as everolimus, is believed to be effective for treatment of TSC-associated lesions because they act on the underlying disease pathophysiology. OBJECTIVE: We evaluated the long-term effect of oral everolimus on TSC-associated skin lesions as a secondary objective in the phase III studies EXIST-1 (NCT00789828) and EXIST-2 (NCT00790400) after approximately 4 years of treatment. MATERIALS AND METHODS: Everolimus was dosed 4.5 mg/m2 /day (titrated to trough 5-15 ng/mL) in patients with TSC-associated subependymal giant cell astrocytoma in EXIST-1, and 10 mg/day initially in adult patients with TSC- or sporadic lymphangioleiomyomatosis-associated renal angiomyolipoma in EXIST-2. Following positive results from the core phase, remaining patients were offered open-label everolimus in an extension. Skin lesion response rate was the proportion of patients achieving complete or partial clinical response. RESULTS: A total of 105 patients in EXIST-1 and 107 in EXIST-2 received everolimus and had ≥1 skin lesion at baseline. Skin lesion response rate (95% confidence interval) was 58.1% (48.1-67.7%) in EXIST-1 and 68.2% (58.5-76.9%) in EXIST-2; most were partial responses. At week 192 (EXIST-1: n = 55; EXIST-2: n = 56), 69% and 66% had a response. Most common drug-related adverse event was stomatitis (41-45%). CONCLUSION: Oral everolimus improved TSC-related skin lesions, with responses sustained over 4 years of treatment in EXIST-1 and EXIST-2.

Persistence of self-injury, aggression and property destruction in children and adults with tuberous sclerosis complex.

BACKGROUND: Individuals with tuberous sclerosis complex (TSC) are at increased risk of developing self-injurious behaviour. The persistence of this deleterious behaviour over years is reported in aetiologically heterogeneous samples to be between 60% and 80% but is unknown for TSC. METHOD: In this study, we determined the 3-year persistence of self-injury in a sample (n = 52) of children (with and without ID) and adults (with ID) with TSC and examined characteristics associated with persistence. RESULTS: Findings for self-injury were contrasted to those for aggression and property destruction to examine the specificity of results to this behaviour. Self-injury was persistent in 84.6% of those with TSC who showed this behaviour, in contrast to 66.7% both for aggression and destruction. Persistent self-injury was associated with poor self-help skills, greater overactivity/impulsivity and more behavioural indicators of pain. These latter two characteristics were also associated with persistent aggression. No characteristics were associated with persistence of property destruction. CONCLUSION: These findings suggest that self-injurious behaviours in individuals with TSC, together with aggressive and destructive behaviours, are highly persistent and would benefit from targeted intervention. Poor adaptive skills, overactivity/impulsivity and painful health conditions may differentiate those at most risk for persistent self-injury or aggression.

Measuring adolescent mental health around the globe: psychometric properties of the self-report Strengths and Difficulties Questionnaire in South Africa, and comparison with UK, Australian and Chinese data.

AIMS: This study evaluated the psychometric properties of the Strengths and Difficulties Questionnaire Self-Report (SDQ-S) in South African adolescents, and compared findings with data from the UK, Australia and China. METHODS: A sample of 3451 South African adolescents in grade 8, the first year of secondary school (Mage = 13.7 years), completed the SDQ-S in Afrikaans, English or isiXhosa. Means, group differences and internal consistency were analysed using SPSS V22, and confirmatory factor analyses were conducted using MPlus V7. RESULTS: In the South African sample, significant gender differences were found for four of the five sub-scale means and for total difficulties, but gender differences of alpha scores were negligible. The internal consistency for the total difficulties, prosocial behaviour and emotional symptoms sub-scales were fair. UK cut-off values for caseness (set to identify the top 10% of scores in a UK sample) led to a higher proportion of South African adolescents classified in the 'abnormal' range on emotional and peer difficulties and a lower proportion classified in the 'abnormal' range for hyperactivity. South African cut-offs were therefore generated. The cross-country comparison with UK, Australian and Chinese data showed that South African adolescent boys and girls had the highest mean scores on total difficulties as well as on the subscales of emotional symptoms and conduct problems. In contrast, South African boys and girls had the lowest mean scores for hyperactivity/inattention. The UK boys and girls had the highest mean scores for hyperactivity/inattention, while the Australian sample had the highest scores for prosocial behaviours. The Chinese boys had the highest peer problem mean scores and Chinese boys and girls had the lowest means on prosocial behaviours. Confirmatory factor analyses showed significant item loadings with loadings higher than 0.40 for the emotional and prosocial behaviour sub-scales on the five-factor model, but not for all relevant items on the other three domains. CONCLUSIONS: Findings support the potential usefulness of the SDQ-S in a South African setting, but suggest that the SDQ-S should not be used with UK cut-off values, and indicate the need for further validation and standardisation work in South African adolescents. We recommend that in-country cut-offs for 'caseness' should be used for clinical purposes in South Africa, that cross-country comparisons should be made with caution, and that further examination of naturalistic clusters and factors of the SDQ should be performed in culturally and contextually diverse settings.

Actinomycosis of the abdominal wall after cholecystectomy: transferral theory.

Abdominal actinomycosis is a rare disease caused by Gram-positive anaerobic Actinomyces bacteria. Here, we present a patient with an intrauterine contraceptive device who developed a long lasting and unexplained recurrent, painful abdominal swelling a few months after a laparoscopic cholecystectomy.

Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome.

AIM: The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. METHODS: Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) levamisole (or placebo) orally once every other day. One hundred and thirty-six plasma samples were collected from 38 children from India and Europe and included in the analysis. A one compartment model described the data well. RESULTS: The apparent clearance rate (CL/F) and distribution volume (V/F) were 44 l h(-1) 70 kg(-1) and 236 l 70 kg(-1) , respectively; estimated interindividual variability was 32-42%. In addition to allometric scaling of CL/F and V/F to body weight, we identified a significant proportional effect of age on CL/F (-10.1% per year). The pharmacokinetics parameters were not affected by gender, tablet strength or study centre. The median (interquartile range) maximum plasma concentration of levamisole was 438.3 (316.5-621.8) ng ml(-1) , and the median area under the concentration-time curve was 2847 (2267-3761) ng ml(-1) h. Median tmax and t½ values were 1.65 (1.32-2.0) h and 2.60 (2.06-3.65) h, respectively. CONCLUSIONS: Here, we present the first pharmacokinetic data regarding levamisole in children with steroid-sensitive nephrotic syndrome. The pharmacokinetic profile of levamisole in children was similar to findings reported in adults, although the elimination rate was slightly higher in children.

Exploratory trial to determine the efficacy of the PYthon and the PYthon Magnum slow-release insecticide ear tags for the control of midges (Culicoides spp.), attacking sheep and cattle and flies attacking cattle.

This study investigated the prophylactic action of the chemical combination zeta-cypermethrin and piperonyl butoxide, administered by means of slow-release insecticide-impregnated ear tags, against biting midges (Culicoides spp) attacking sheep and against midges, horn flies (Haematobia irritant), stable flies (Stomoxys calcitrans), and houseflies (Musca domestica) attacking cattle. Treated sheep and cattle were protected 100 percent against blood-feeding midges for two months and there was a clear reduction in the number of midges collected from treated animals. Three days after the ear tags were attached to cattle, the number of horn flies on the cattle was reduced to practically zero and remained at a low level until the end of the trial (day 85). There was also a strong reduction in the numbers of stable flies and houseflies counted.

Infectious diseases among travellers and migrants in Europe, EuroTravNet 2010.

To investigate trends in travel-associated morbidity with particular emphasis on emerging infections with the potential for introduction into Europe, diagnoses of 7,408 returning travellers presenting to 16 EuroTravNet sites in 2010 were compared with 2008 and 2009. A significant increase in reported Plasmodium falciparum malaria (n=361 (6% of all travel-related morbidity) vs. n=254 (4%) and 260 (5%); p<0.001), P. vivax malaria (n=51 (1%) vs. n=31 (0.5%) and 38 (1%); p=0.027) and dengue fever (n=299 (5%) vs. n=127 (2%) and 127 (2%); p<0.001) was observed. Giardia lamblia was identified in 16% of patients with acute diarrhoea, with no significant annual variation. The proportion of acute diarrhoea due to Campylobacter increased from 7% in 2008 to 12% in 2010 (p=0.001). We recorded 121 patients with pulmonary tuberculosis in 2010, a threefold increase in the proportionate morbidity from 2008 to 2010. In 2010, 60 (0.8%) cases of chronic Chagas disease, 151 (2%) cases of schistosomiasis and 112 (2%) cases of cutaneous larva migrans were reported. Illness patterns in sentinel travellers, captured by EuroTravnet, continue to highlight the potential role of travellers in the emergence of infectious diseases of public health concern in Europe and the relevance of offering medical travel advice and enforcing specific and adequate prophylaxis.

Severe pulmonary manifestation of leptospirosis.

Based on increasing incidence and the occurrence of worldwide outbreaks, leptospirosis is recognised as an emerging zoonosis. Severe manifestations are associated with high morbidity and mortality rates and may therefore pose an important risk to public health, especially in certain high prevalence areas. A considerable number of infections progress to a severe form, which can present as the well-known triad of jaundice, impaired renal function and haemorrhage, known as Weil's disease. The severe pulmonary form of leptospirosis (SPFL) is a less known entity and is characterised by intra-alveolar haemorrhage and can lead to acute respiratory failure and death when adequate treatment fails. Prognostic factors correlating with severity and survival of leptospirosis include indicators of renal failure, pulmonary involvement and electrolyte imbalances. We report an imported case of SPFL in a returning traveller, and review the literature discussing epidemiology, clinical manifestations, prognostic factors and treatment of this resurgent disease.

Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice.

Approximately 40-50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASDs). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. In this study, we report the interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single, exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.

High incidence of peripheral blood plasmacytosis in patients with dengue virus infection.

Little is known about polyclonal peripheral blood plasmacytosis in dengue virus (DENV)-infected patients. We initiated this prospective observational study to quantify and describe the kinetics and phenotype of peripheral blood plasma cells (PCs) in these patients. Morphological examination and flow cytometric (FC) analysis for the characterization and immunophenotyping of lymphocyte subsets and PCs were performed in 35 and 31 patients suspected of DENV infection, respectively. Our results show that blood plasmacytosis is a very common haematological finding. Depending on the days of illness at presentation, blood plasmacytosis was observed in 64% to 73% of patients. Blood plasmacytosis was most pronounced before 7 days of illness and declined rapidly thereafter, to completely disappear after 14 days of illness. Blood plasmacytosis was higher in secondary DENV infection. The majority of CD138(+) PCs (89%) had a shared immunophenotype (CD45(+)/CD19(-)/CD56(-)) and in all cases the PCs were polyclonal. Blood plasmacytosis, characterized by a transient presence of polyclonal PCs in the circulation, is a common event in DENV infection.

Geographical heterogeneity of dengue transmission in two villages in southern Vietnam.

This study was performed to test the hypothesis that there are 'hotspots', i.e. geographical heterogeneity, of dengue transmission. Data from two repeat serosurveys in two villages in Vietnam were used to identify incident infections and to relate these to prevalence at baseline and thus assess geographical heterogeneity, i.e. clustering, in dengue transmission. A total of 400 households were surveyed; serological data from 521 children at baseline and from 119 children at follow-up were included in a spatial analysis. Geographical heterogeneity of dengue transmission was explored using a permutation null distribution test. This showed for the first time evidence of clustering of dengue virus transmission at the household level in asymptomatic children. Risk areas could be identified by seroprevalence surveys combined with mapping. Control of dengue virus transmission could be supported by identification and control of hotspots.

Miltefosine treatment of Leishmania major infection: an observational study involving Dutch military personnel returning from northern Afghanistan.

In a retrospective, observational study involving 34 patients with Leishmania major infection, 31 of whom had experienced unsuccessful treatment with intralesional antimony (ilSb(v)), miltefosine proved effective. Thirty patients experienced cure after receipt of miltefosine, 3 after receipt of additional ilSb(v), and 1 after 28 daily intravenous injections of antimony. Temporary diminution of ejaculate volume was reported by 21 patients.