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Background Gastrointestinal illness is a major cause of morbidity in travellers and is a common reason for presentation to healthcare services on return. Whilst the aetiology of imported gastrointestinal disease is predominantly infectious, outcomes are variable due to a range of phenomena such as post-infectious irritable bowel syndrome, drug resistance and occult pathology (both infectious and non-infectious). Previous studies have focussed on predictors of aetiology of gastrointestinal disease in travellers; we present a retrospective study combining both aetiological and early outcome data in a large cohort of returned travellers. Method We identified 1450 patients who attended our post-travel walk-in clinic with gastrointestinal symptoms between 2010 and 2016. Demographic, travel, clinical and laboratory data was collected through case note review. Logistic regression analysis to examine correlates of aetiology and outcome were performed in R (CRAN Project 2017). Results Of 1450 patients in our cohort 153 reported bloody diarrhoea and 1081 (74.6%) reported non-bloody diarrhoea. A definitive microbiological diagnosis was made in 310 (20.8%) of which 137 (9.4%) had a parasite identified and 111 (7.7%) had a bacterial cause identified. Factors associated with a parasitological diagnosis included history of travel to South Asia (aOR = 2.55; 95%CI 1.75–3.70, p p p p p 5iu/dL (aOR = 4.68; 95%CI 2.91–7.72, p p p p Conclusions In a cohort of returned travellers, we were able to identify multiple factors that are correlated with both aetiology and outcome of imported gastrointestinal syndromes. We predict these data will be valuable in the development of diagnostic and therapeutic pathways for patients with imported gastrointestinal infections.

The purpose of this case study series was to assess improvement in the quality of life, function, and colonic motility before and after visceral and neural manipulation in five children with cerebral palsy and chronic constipation who had Gross Motor Function Classification System (GMFCS) levels of IV and V. Quality of life and function were assessed using the CPCHILD and the WeeFIM respectively. The CPCHILD and WeeFIM were administered at baseline before the intervention, after the intervention, and again at least three months post intervention. Colonic motility was assessed radiographically at baseline and post-intervention utilizing ingested radiopaque markers (Sitz markers). Bowel movement number and quality were assessed through family diaries. All subjects showed some degree of improved quality of life and function on the CPCHILD and WeeFIM at the end of the intervention. Colonic motility assessed radiographically before and after treatment was not statistically significant due to the small number of participants; however, the number of bowel movements increased during the study for 100% of the participants. Visceral and neural manipulation modalities may provide clinicians and families with an alternative to medications and/or other more invasive interventions.

The Samarco tailings dam broke on 5 November 2015, sending a wall of mud into the Bento Rodrigues township and killing 19 people. From there the mud made its way to the Rio Doce river system, killing fish and frogs, and causing massive pollution down to the mouth 650 km away. A year later a yellow fever outbreak occurred in the same state in Brazil, with 450 confirmed cases and about 150 deaths. After newspapers reported the yellow fever cases, online blogs started suggesting that the outbreak might have been caused by the Samarco disaster and citing comments by well-known scientists. Twelve months later another yellow fever outbreak occurred, and the online bloggers repeated the same claims, but the wording changed. In this paper we analyze the timing of the online activity, using Google search to find all the postings in the press and in social media with the two terms, “Samarco” and “Febre Amarela” (yellow fever, in Portuguese). In 2017, most postings faithfully reported what the scientists had said, but in 2018, some postings started making stronger claims than the scientists originally had. After analyzing the content of the postings, we construct two directed networks, one for 2017 and the other for 2018, to show to which scientists the postings refer and to illustrate the subtle and not so subtle distortions that started to creep in. In the conclusion we ask how the rise in hostility to mining expressed in some of these blogs should be interpreted. Is it just the usual low-level dislike of the extractive industries or are these the precursor symptoms of a more general refusal to accept mining in Brazil?

Summary Introduction Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data. Methods Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 10 9 /L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre. Results Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002–2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997–2002) to 17% (2002–2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378–0.778 p = 0.0009). Discussion A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield.

This study describes the clinical features of a cohort of imported cases of strongyloidiasis and the performance of standard diagnostic techniques for this condition. A total of 413 cases were identified, of whom 86 had microscopically proven infection. In proven cases, 23% had normal eosinophil counts, 19% had negative Strongyloides-specific serology, and 9.3% had normal blood counts and were seronegative. Serological testing was less sensitive for returning travelers (46.2%) than for migrants (89.7%). Immunosuppression, including human T-cell lymphotropic virus 1, was significantly associated with proven infection after controlling for age, presence of symptoms, duration of infection, and eosinophilia (OR 5.60, 95% CI 1.54–20.4). Patients with proven infection had lower serology values than those diagnosed with strongyloidiasis on the basis of positive serology and eosinophilia alone (P = 0.016). Symptomatic patients were significantly younger, had a shorter presumed duration of infection, and lower serology values. These data suggest a correlation between immunologic control of strongyloidiasis and the amplitude of the humoral response.

Objectives: Prednisolone and thalidomide are commonly used in the management of erythema nodosum leprosum (ENL) and bring relief to patients with this condition worldwide. However, both ENL and its treatments can cause significant morbidity. This study describes the spectrum of ENL seen at The Hospital for Tropical Diseases, London (HTD), the use of steroids and thalidomide in its management and the complications of their use. Study Design: We conducted a retrospective audit of patients diagnosed with ENL between 1996 and 2013. Data were obtained from hospital records including severity and length of disease, together with treatments received and adverse effects. Results: Between 1996 and 2013, 30 patients were diagnosed with ENL. The median bacillary index (BI) at diagnosis was 4·65, higher than in previous studies. Most patients developed ENL during leprosy treatment (67%) and had chronic ENL (57%). The median length of ENL was 60 months (range 9 – 192); patients with BI . 4·5 had significantly longer duration of disease. 87% patients received prednisolone for median nine months; 35% developed adverse effects including diabetes and hypertension. 87% patients received thalidomide for median 16 months; 65% complained of side effects. There were no pregnancies or venous thromboembolisms. 77% patients stopped prednisolone within two months of starting thalidomide. There were no deaths in our cohort. Conclusion: We describe the clinical course of ENL in a non-endemic country with access to thalidomide and prednisolone. ENL may last far longer than previously described and has significant impact on a patient’s health. In the UK, thalidomide is essential as a steroid-sparing agent, to prevent the adverse effects and mortality of long-term steroids which have been documented elsewhere.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.

We present two probabilistic models to estimate the risk of introducing infectious diseases into previously unaffected countries/regions by infective travellers. We analyse two distinct situations, one dealing with a directly transmitted infection (measles in Italy in 2017) and one dealing with a vector-borne infection (Zika virus in Rio de Janeiro, which may happen in the future). To calculate the risk in the first scenario, we used a simple, nonhomogeneous birth process. The second model proposed in this paper provides a way to calculate the probability that local mosquitoes become infected by the arrival of a single infective traveller during his/her infectiousness period. The result of the risk of measles invasion of Italy was of 93% and the result of the risk of Zika virus invasion of Rio de Janeiro was of 22%.

Summary Objectives To establish the clinical reasons for inpatient admissions among injecting drug users. To determine the frequency of behavioural issues during their care and to estimate the financial implications of injecting drug use to the health service. Methods Retrospective cohort study at University College London Hospital. Clinical, laboratory and financial data were extracted from case notes and electronic records. The cost of each admission was compared to the income received for the period of care. Results 124 injecting drug users required 191 admissions between 2005 and 2009. Skin and soft tissue infections (58%) and pneumonia (18%) were the commonest reasons for admission. Bacteraemia at admission was often not accompanied by an inflammatory response. Exposure to HIV (4%), hepatitis B (49%) and C (84%) was common. Drug misuse (16%) during admission was frequent. The cost to the NHS of treating soft tissue infections in drug users was approximately £77 million per annum. After a median follow-up of 40 months, 10 patients (8%) had died. All deaths were attributable to drug use. Conclusions Bacterial and viral infections are largely responsible for the significant mortality and morbidity of injecting drug users presenting to secondary care. The financial burden to the NHS is substantial.

International audience; Objectives: The recent emergence of Zika in Brazil and its association with an increased rate of congenital malformations has raised concerns over its impact on the birth rate in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-2016 for the city of Rio de Janeiro (population 6.4 million), a massive increase of Zika in women compared to men was documented.Methods: The age-adjusted incidence was compared between men and women. A negative binomial Poisson generalized linear model was fitted to the Zika incidence data to determine the significance of sexual transmission statistically.Results: Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there were found to be 90% more registered cases per 100 000 women than men in the sexually active age group (15-65 years); this was not the case for age groups < 15 years and > 65 years. Assuming that infected men transmit the disease to women in their semen, but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, the incidence of dengue fever was compared in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women were 30% more likely to be reported with dengue.Conclusion: Women in the sexually active age group are far more likely to get Zika than men (+ 90% increase); sexual transmission is the most probable cause. Women in the 15-65 years age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.

Summary Background: The probability that a returned traveller with a history of fever has malaria is likely to vary by geographical area, but this has not been quantified in travellers. Aim: To collect data on prevalence of malaria in outpatients returning with a fever or history of fever from malaria-endemic countries, at the point of presentation for a malaria test. Design: Observational retrospective study. Consecutive patients presenting to an unselected ‘walk-in’ clinic for returned travellers. Results: Of 2867 patients meeting inclusion criteria, 337 (11.8%) had malaria, 89.5% originating in sub-Saharan Africa. Of travellers returning from sub-Saharan Africa excluding South Africa with fever/ history of fever, 291/1497 had malaria (19.4%, 95% CI 17–21%). A high proportion was visiting friends and relatives. In those from other areas the proportions were: 16/707 (2.3%, 95% CI 1.5–3.8) from Indian subcontinent/Southeast Asia; 2/143 (1.4%) from Southern America; 4/129 (3.1%) from South Africa; 1/44 (2.3%) from North Africa; and 8/41 (19.5%) from Oceania. Compared to other malaria-endemic regions, African travel gave an adjusted odds ratio of 7.8 (95% CI 5.4–11.2, P < 0.0001). Only 45.1% of malaria cases had a fever (37.58C) at the time of presentation. Only 3% of all diagnoses of malaria had no history of fever. In 28% of cases parasite count increased in the initial 24 h of antimalarial treatment. Conclusions: The likelihood that a patient with fever returning from Africa has malaria is high (around 1 in 5), and is significantly lower from other areas. Absence of fever at presentation does not exclude malaria.

Just more than 2,000 cases of Plasmodium falciparum malaria are reported in the United Kingdom annually, with a mortality rate of approximately 1%. Some studies suggest that patients with malaria who originate from disease-endemic areas are less likely to develop severe disease; such patients are often treated at home. We have prospectively examined 99 patients with imported P. falciparum malaria and categorized them according to severity as defined by World Health Organization criteria. There was no significant difference between those who developed severe disease and those who did not in terms of their ethnicity, residence in a malaria-endemic area, or history of previous episodes of malaria. To assume a patient has clinical immunity to malaria simply because they originate from or have lived for a long time in a malaria-endemic area may be inappropriate and unsafe.

Use of parenteral pentavalent antimonials to treat leishmaniasis is associated with a range of cardiological, biochemical and haematological adverse effects. The most serious of these is the development of ventricular tachyarrhythmias associated with prolongation of the electrocardiographic rate-corrected QT interval (QTc). Whereas some studies have reported that serious cardiological and biochemical adverse effects are common and often require treatment interruption or discontinuation, others have reported the drugs to be well tolerated. We conducted a detailed retrospective analysis of adverse events among British returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of treatment and the QTc reached the threshold for potential cardiac toxicity among 6 (10%) patients during the third week of treatment. Marked QTc prolongation and ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia and pre-existing cardiovascular morbidity. Although increased serum concentrations of amylase and hepatic transaminases were observed among 67% and 85% of patients respectively, none developed clinical pancreatitis or hepatitis and treatment modification was not required. SbV can be used safely in this population with adequate monitoring and the need for treatment interruption is uncommon. Identification of factors before and during treatment that may increase the risk of QTc prolongation and arrhythmias is important.

Problem Introduction and evaluation of evidence based medicine (EBM) into routine hospital practice. Strategy for change Routine EBM meetings introduced in 1997. Design Review of outcomes of meetings from 1997 to 2004, focusing on their effect on clinical practice. Setting Referral centre for tropical and domestic infectious diseases. Key measure for improvement Outcome of meetings, classified as resulting in a change in practice; confirmation or clarification of existing practice; identification of a need for more evidence; and outcome unclear. Effects of change Examples include a change from inpatient to day case treatment of New World cutaneous leishmaniasis; development of guidelines on the treatment of coinfection with visceral leishmaniasis and HIV; and identification of the need for more data on the efficacy and toxicity of atovaquone-proguanil (Malarone) compared with quinine plus sulfadoxine-pyrimethamine (Fansidar) in the treatment of uncomplicated falciparum malaria, which resulted in a clinical trial being set up. Lessons learnt Incorporation of EBM meetings into our routine practice has resulted in treatment guidelines being more closely based on published evidence and improvements to care of patients. Written summaries of the meetings are important to facilitate change.

Background: Patients from malaria-endemic areas who present in non-endemic countries with Plasmodium falciparum malaria are often assumed to have some degree of immunity. If this were reliably true, it would simplify their management. Aim: To determine whether being born and resident in a malaria-endemic country is a predictor of clinical course in UK admissions for malaria. Design: Prospective observational study. Methods: We compared clinical and laboratory parameters between two groups of adult patients with acute P. falciparum malaria, admitted to the Hospital for Tropical Diseases in London: one born and resident in non-endemic countries ( n = 167); the other born and resident in malaria-endemic countries of Africa ( n = 93). Patients were excluded if they had taken prophylaxis or prior treatment. Results: There were no differences between these two groups in terms of peak parasitaemia or time to parasite clearance. There was a significantly higher risk of malaria-naive patients having peak parasitaemia >5% (OR 4.5, 95%CI 1.5–13.2). Of those usually resident in Africa, 31% required parenteral treatment compared to 41% of the malaria-naive group. Of the visitors from Africa, 4.3% needed admission to the Intensive Therapy Unit (ITU), although there was a tendency for more malaria-naive patients to require ITU care (OR 2.69, 95%CI 0.9–8.1). Discussion: While there are differences in presentation between those who are malaria-naive and those who live in malaria-endemic African countries, making assumptions about the immunity or clinical course of an individual patient with malaria presenting in the UK on the basis of presumed history of exposure is unwise.

Objectives: Patients with eosinophilia are an important clinical problem. This study aimed to assess the most efficient manner of investigating patients with peripheral eosinophilia (eosinophil count >0.5×10 9 ml −1 ) presenting from the tropics. Methods: Patients attending the Hospital for Tropical Diseases, London, from October 1997 to March 2002 for investigation of eosinophilia were identified prospectively. Laboratory, clinical and demographic data were recorded from laboratory and clinical records. An investigation set was proposed prospectively and assessed for all geographical areas (stool microscopy, strongyloides culture and serology), all of Africa (additional schistosomal serology, terminal urine microscopy and filarial serology) and West Africa (additional day-bloods for microfilaria). Results: Data was analysed for 261 patients. At least one helminthic cause for eosinophilia was found in 64% of patients (median eosinophilia 1.2×10 9 ml −1 ). Seventeen per cent of patients had more than one helminth species found. Median eosinophilia increased with number of diagnoses per patient. The proposed investigation sets were validated, with high yield for all proposed tests apart from filarial serology outside West Africa, and good sensitivity. Conclusions: Initial investigation of eosinophilia in patients presenting from the tropics may be guided by a simple investigation set depending on broad area of travel which has high sensitivity and yield. Patients frequently have more than one helminthic cause of eosinophilia.

Schistosomiasis is found in a significant proportion of returning travellers and immigrants to Britain. This study is a retrospective review of 1107 consecutive cases of schistosomiasis from Africa diagnosed by microscopy or serology presenting to the Hospital for Tropical Diseases, London, UK. 50·4% of cases were asymptomatic. The most common symptom which resolved on treatment was tiredness. Serology was positive in 951 (86%), and ova seen in 45%. Urine dipstick testing was positive for blood in 21% and protein in 15%, with eosinophilia in 44%. In this population urine dipstick, full blood count and serology were all insufficient screening tools used alone. Among patients with full follow-up data 3 months or more after treatment with praziquantel, definite treatment failure occured in 4 of 271 (1·5%), restricting the analysis to those with ova seen at diagnosis. There was no significant difference in treatment failure between 1 and 3 days of treatment. Antibody level was the same or higher than at treatment in 55% of cases seen after about 3 months and 38% after 1 year, confirming it is probably of limited clinical use in detecting treatment failure.

Objectives We sought to identify chloroquine-resistant Plasmodium falciparum parasites among 66 travellers who presented in the UK with malaria. Methods A multiplex real-time PCR assay was devised to identify wild-type and two distinct chloroquine-resistance-associated alleles of the pfcrt gene. Results Those with documented use of chloroquine/proguanil prophylaxis were more likely to carry parasites with resistance-associated alleles of pfcrt than were patients who had been using antimalarials other than chloroquine (92.9% versus 37.5%; P = 0.011). We also found evidence that people reporting optimum compliance with chloroquine prophylaxis during malaria exposure were more common among malaria cases than were those reporting optimum compliance with other regimens (OR 3.85, 95% CI 1.61-9.69; P = 0.0008). Conclusions Chloroquine, known to be failing as therapy for falciparum malaria worldwide, is also failing to provide adequate malaria prophylaxis for travellers.

We report 79 cases of acute schistosomiasis. Most of these cases were young, male travelers who acquired their infection in Lake Malawi. Twelve had a normal eosinophil count at presentation and 11 had negative serology, although two had neither eosinophilia nor positive serology when first seen. Acute schistosomiasis should be considered in any febrile traveler with a history of fresh water exposure in an endemic area once malaria has been excluded.

(See the major article by Hopkins et al on pages 645–57.) Since the 1880s, the standard diagnostic test for malaria has been microscopic examination of peripheral blood smears [1–3]. The development of rapid antigen-detection tests (RDTs) in the early 1990s has improved diagnosis of Plasmodium infection in malaria-endemic countries and targeting of treatment [4, 5]. In countries where malaria is not endemic, where imported malaria cases in travelers can be mistaken for nonspecific viral illness [6, 7], causing delay in diagnosis and in some cases progression to severe illness and death [8–11], RDTs have improved the capacity for rapid malaria diagnosis by nonspecialist health workers [12–15]. While RDTs and expert microscopy are considered adequate for case management in malaria-endemic populations [16], there is growing interest in “improvements in point-of-care tests for case management, and the development of new tests capable of identifying very low parasite densities in asymptomatic individuals in field settings for mass screening and treatment” [17]. Polymerase chain reaction (PCR), in its most sensitive form, has a limit of detection as low as 50 parasites per milliliter of peripheral blood [18, 19], although results take 10–16 hours, whereas expert microscopy is less sensitive but routinely produces results in 60 minutes. Real-time quantitative PCR (qPCR) can reliably detect parasite DNA within 3–5 hours of sample receipt but is also less sensitive than nested PCR [20]. Recent studies show that loop-mediated amplification (LAMP) assays for malaria, which deploy isothermal molecular amplification in a closed system with visual readout, can deliver PCR-level diagnostic accuracy in a little more than 1 hour, with lower laboratory capacity requirements [21–23]. To date, malaria LAMP has not been available in a format suited to routine diagnosis in the clinic. A clinically validated, CE-marked assay would be an attractive alternative to RDT and microscopy in settings where malaria is or is not endemic. A malaria LAMP kit has been developed as a point-of-care diagnostic test, and after CE marking it was released commercially in mid-2012. This kit comprises a disposable extraction device and tubes containing vacuum-dried and temperature-stable reaction components. We investigated the diagnostic accuracy of this kit for case management in a study of sequential blood samples from suspected imported malaria cases received by a specialist parasitology laboratory in London, United Kingdom, over the first 7 months of 2011. Primary diagnosis was by expert microscopic examination of blood films. An established nested PCR assay was deployed as the reference standard [18]. Diagnostic accuracy of the new kit was superior to that of microscopy and similar to that of nested PCR but with the additional benefits of reduced assay time and ease of operation.

Background Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. Methods Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. Results Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. Conclusions The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease.

Background Malaria is the commonest imported infection in the UK. Malaria requiring ICU admission has a reported mortality of up to 25%. The relationship between ethnicity, immunity, and risk of malaria is complex. The Malaria Score for Adults (MSA) and Coma Acidosis Malaria (CAM) score have recently been proposed to risk stratify patients with malaria. Methods Retrospective study of patients with WHO severe falciparum malaria admitted to ICU at the Hospital for Tropical Diseases, London, UK. The relationship between clinical variables and risk of death or a prolonged ICU stay were examined with logistic regression. The predictive value of the MSA and CAM score were calculated. Results 124 patients were included. Cerebral malaria and acute kidney injury occurred earlier (median day 1) than acute respiratory distress syndrome (median day 3). Six patients had community acquired bacterial co-infection. Eight patients were co-infected with HIV, five of whom were newly diagnosed. The positive predictive value of a CAM score ≥2 or an MSA ≥5 for death were 12% and 22% respectively. Five patients died. No variable was significantly associated with risk of death. There were no significant differences between individuals raised in endemic countries compared to non-endemic countries. Conclusions Mortality in patients managed in a specialist centre was low. Patients who died succumbed to complications associated with a prolonged stay on ICU rather than malaria per se. The clinical usefulness of the MSA and CAM score was limited. Co-infection with HIV was relatively common but compared to studies in children, bacteraemia was uncommon. The relationship between ethnicity and immunity to severe disease is complex.

Background: Few studies have investigated incidence rate and risk factors for giardiasis and strongyloidiasis in returning UK travellers. The clinical presentations of these two diseases are often similar and difficult to distinguish. This study was conducted to investigate the incidence rate and the risk factors for symptomatic giardiasis and strongyloidiasis in returned tropical travellers. Methods: We retrospectively analysed 3306 consecutive attendances presenting to the emergency clinic at the Hospital for Tropical Diseases in London, the UK from September 2008 to May 2010. Odds ratios between the diagnoses and patient variables were analysed by logistic regression. Results: Giardiasis was diagnosed in 92/3306 cases (2.8%, proportionate morbidity), and the incidence rate per 1000 person-months was 12.5. Multivariate analysis with logistic regression revealed that Caucasian ethnicity (adjusted odds ratio (aOR): 2.37, 95% confidence interval (CI): 1.12–5.03, P value = 0.025), travel length ≥32 days (aOR: 2.63, 95%CI: 1.43–4.83, P = 0.002), travelling to South or South East Asia (aOR: 4.90, 95%CI: 2.03–11.8, P

BACKGROUND: Early diagnosis of HIV infection reduces morbidity and mortality associated with late presentation. Despite UK guidelines, the HIV testing rate has not increased. We have introduced universal HIV screening in an open-access returning traveller clinic. METHODS: Data were prospectively recorded for all patients attending the open-access returning traveller clinic between August 2008 and December 2010. HIV testing was offered to all patients from May 2009; initially testing with laboratory samples (phase 1) and subsequently a point-of-care test (POCT) (phase 2). RESULTS: A total of 4965 patients attended the clinic; 1342 in phase 0, 792 in phase 1 and 2831 in phase 2. Testing rates for HIV increased significantly from 2% (38 of 1342) in phase 0 to 23.1% (183 of 792) in phase 1 and further increased to 44.5% (1261 of 2831) during phase 2 (P

Background Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach. Methodology We reviewed records of 67 consecutive NWCL patients, aged 17–61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity. Principal Findings Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×109/L (CI 0.29×109/L to 0.76×109/L, p, Author Summary Sodium stibogluconate (SbV), a pentavalent antimonial, administered parenterally, is the recommended treatment for South American cutaneous leishmaniasis, caused by Leishmania Viannia, which is a neglected disease that affects many people resident in Central and South America, as well as travellers to the areas. Antimonials have been used for the treatment of leishmaniasis since the 1930s. We report the toxicity experienced by a series of NWCL patients receiving SbV in a resource-rich setting. This study also evaluates administration of the drug to patients without admitting them to hospital. The administration of parenteral SbV was associated with myelosuppression, derangement of markers of liver function and prolongation of the QT interval on electrocardiography, although these effects were not found to be associated with adverse clinical events, and the majority of doses of SbV were administered without cause for hospital admission. Our data shows that parenteral SbV treatment may be provided with reduced monitoring for toxicity than is currently done, and on an outpatient-basis, without endangering safety. Such practice, with reduced demands on local finances and the healthcare workforce, would be desirable in more resource-limited settings.

This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998–2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were in soldiers. Polymerase chain reaction was more sensitive and faster for detecting Leishmania DNA (86% for Old World CL and 96% for New World CL) than culture. This is the largest study of imported leishmaniasis, and demonstrates that tourists to the Mediterranean and backpackers in Central and South America are at risk for this disease.

Our current knowledge of the clinical characteristics of enteric fever is drawn mainly from population-based studies in disease-endemic countries, and there are limited data published on cases in returning travelers. We report the clinical characteristics of enteric fever in 92 travelers returning to London, United Kingdom. Salmonella typhi and S. paratyphi resulted in an almost indistinguishable clinical picture. Rose spots and relative bradycardia were found only in a few patients. A total of 91% of the patients had a normal leukocyte count, which was associated with a markedly increased level of alanine aminotransferase in 82%. A total of 57% of the S. typhi isolates had decreased susceptibility to ciprofloxacin and resistance to nalidixic acid; these isolates were from southern Asia. Thirty percent were multidrug resistant; all were from southern Asia and Nigeria. None of the paratyphoid isolates were multidrug resistant but rates of decreased susceptibility to fluoroquinolones were higher than in S. typhi (74%).

Background: Stroke units and thrombolysis are evidence based treatments for stroke patients. Few studies have prospectively assessed the success of, and obstacles to implementation of such strategies in patients admitted to district general hospitals. Objective: To document delays in admissions of acute stroke patients to hospital, failures in accessing a stroke unit and the clinical impact of missed opportunities for intervention in acute stroke patients. Design, setting and methods: Prospective observational study in a district general hospital in Northern Ireland. Delays, demographic details, risk factors, stroke severity and classification were recorded prospectively in all stroke patients admitted to a district general hospital from 22 March 2004 until 21 March 2005. Using established numbers needed to treat to prevent disability or death, the clinical impact of the lost opportunities was determined. Results: Of 171 acute stroke patients 115 (67%) spent some or all of their hospital stay in a stroke unit. Less severe strokes, living alone and attending a general practitioner all independently delayed hospital admission. Nineteen (12.5%) ischaemic stroke patients would have been eligible for intravenous thrombolysis treatment. Admitting all patients to the stroke unit would have gained independence for two patients, allowed two more patients to live at home, and prevented one death. Failure to thrombolyse eligible acute ischaemic stroke patients resulted in six patients having more disability, two of whom may have lost their independence. Conclusions: Improved stroke unit access is required in this district general hospital. Reorganisation of acute stroke services should allow thrombolysis for acute ischaemic stroke in most district general hospitals.

The European working time directive (EWTD) was introduced into National Health Service hospitals for doctors in training in August 2004.1 Mounting evidence had shown that fatigue in doctors contributes to adverse events in patients.2 However, the implementation of potential quality improvements requires an understanding of whole healthcare systems.3 Before the introduction of the EWTD, our stroke ward had a resident senior house officer who provided weekday care, ensuring that all patients were medically reviewed on a daily basis. This is required, …

Background: Malaria is currently diagnosed almost exclusively by microscopy in clinical laboratories. The introduction of rapid diagnostic tests (RDTs) may be useful in achieving rapid detection of malaria parasites, especially in situations where malaria is not often seen or where staff are inexperienced. Aim: To explore the use of RDT in UK laboratories. Methods: The current use of RDTs was surveyed in UK laboratories subscribing to the United Kingdom National External Quality Assessment Scheme blood parasitology and haematology schemes. Results: An overall survey response rate of 60.3% was seen. RDTs were found to be the preferred choice, either alone or in conjunction with microscopy in 31.2% of the samples examined during normal working hours and in 44.3% of the specimens examined on call. Conclusions: During on-call hours, the use of RDTs was observed to increase and RDTs changed the diagnosis in 12% of laboratories. No established protocol for RDT use was, however, observed in the UK. A protocol that needs to be validated in the laboratory setting is suggested.

Towards rehabilitative handling in caring for patients following stroke: a participatory action research project Aim of the study. This study aimed to facilitate nurses to take ownership of their moving and handling practice. Objectives. To (i) facilitate nurses in sharing their insights in moving and handling patients following stroke, (ii) enable nurses to identify facilitators of safer moving and handling practice, and (iii) empower nurses in collaboration with physiotherapists to direct changes in their practice. Background. Traditional top down moving and handling training has had variable impact on nursing practice. A moving and handling incident in a stroke unit demonstrated that there were professional development needs for staff in the stroke unit in relation to their moving and handling practice in the care of patients following stroke. Methods. An insider participatory action research approach was utilized. Data were analysed from focus group meetings, brainstorming sessions, observational studies, and from written reflective accounts. Findings. Peer pressure, communication, rehabilitative handling awareness, teamwork between nurses and physiotherapists, equipment and environmental issues were affecting moving and handling practice. Nurses identified that equipment, environment, communication and teamwork strategies would facilitate them in using rehabilitative moving and handling practice. Nurses in collaboration with physiotherapists directed changes in their practice. Participant staff members felt involved and valued, and reported changes in understanding, in their handling practice, and enhanced teamwork. Conclusion. Participatory action research creates a supportive environment, where those directly involved in moving and handling patients can investigate and direct changes in their practice. Thus it is a significant vehicle for delivering professional development in moving and handling practice. Relevance to clinical practice. Professional development initiatives in moving and handling practice must incorporate processes that enhance inter-disciplinary teamwork and value and utilize the views and experiences of the staff who move and handle patients.

To find out whether serology can reliably speciate human schistosomiasis using a simple enzyme linked immunosorbent assay (ELISA) technique.Stored sera from 66 patients with microscopically confirmed schistosomiasis were subjected to ELISA using a panel of three antigens, namely: unfractionated Schistosoma mansoni soluble egg antigen (SEA); CEF6, a cationic fraction of SEA; and crude S margrebowiei egg antigen, prepared from an animal schistosome closely related to S haematobium.The optical densities (ODs) obtained using CEF6 as antigen were significantly higher in sera from S mansoni infected patients than in sera from S haematobium infected patients (median OD, 0.810 v 0.595). Using S margrebowiei egg antigen, the optical densities were significantly higher in S haematobium sera than in S mansoni sera (median OD, 0.794 v 0.544). There was no significant difference in optical densities between S mansoni and S haematobium sera using SEA (median OD, 0.725 v 0.737). The ratio of ODs (CEF6 to S margrebowiei egg antigen) was calculated: a ratio of1 indicated S mansoni infection (sensitivity, 88%) and a ratio of1 indicated S haematobium infection (sensitivity, 84%). The odds ratio for S haematobium having an OD ratio of1 was 36.8 (95% confidence interval, 7.0 to 194).The identity of the infecting species of schistosome can be determined using the panel of antigens described. SEA should be used to screen serum samples, and the CEF6 : S margrebowiei egg antigen ELISA optical density ratio can be used where serological speciation is required.

Summary Background Leishmania species that occur within different geographical areas may cause different clinical manifestations, virulence and drug sensitivity. Patients/Methods. All patients with a clinical diagnosis of cutaneous leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were identified and clinical details recorded onto a database, with emphasis on clinical presentation, risk factors, travel history and laboratory diagnosis. Results Forty-two patients were identified, 23 of whom had travelled to New World and 19 to Old World countries. Clinical presentation typically consisted of a single nodule with ulceration. In 50% infection was caused by L. (Viannia) braziliensis . PCR was performed in specimens from 34 patients and species identification was possible in 32 cases (sensitivity 94%), the two PCR negative patients had amastigotes demonstrated by histology and culture. Patients were treated with established therapies. Seventy one percent were cured by treatment, 12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10% required a second-line therapy. No relapses were reported during a mean follow-up period of 27 months. Conclusions Our study highlights the need for comprehensive investigations and the advantages of PCR in the diagnosis of patients with suspected leishmaniasis in non-endemic regions of the world.

After observing an apparent increase in severe falciparum malaria among travellers returning from The Gambia to the United Kingdom (UK) in the last quarter of 2000, we conducted a case-control study to investigate risk factors for malaria. The study participants had visited The Gambia between 1 September and 31 December 2000, travelling with the largest UK tour operator serving this destination. The main outcome measures were risk factors associated with malaria. Forty-six cases and 557 controls were studied. Eighty-seven percent of all participants reported antimalarial use (41% chloroquine/proguanil, 31% mefloquine). On univariate analysis the strongest risk factors for disease were: early calendar period of visit, longer duration of stay, non-use of antimalarial prophylaxis, non-use of mefloquine, lack of room air-conditioning, less use of insect repellent, prior visit to another malarial area and accommodation in ‘hotel X’. After adjustment in multivariate analysis, use of mefloquine remained strongly protective (odds ratios, OR 0.13 [95% confidence intervals, 95% CI 0.04–0.40]), and the strongest independent risk factors for malaria were early calendar period (OR 5.19 [2.35–11.45] for 1 September to 9 November 2000 versus 10 November to 31 December 2000), prior visit to another malarial area (OR 3.27 [1.41–7.56]), main accommodation in ‘hotel X’ (OR 3.24 [1.51–6.97]) and duration of stay (OR 2.05 per extra week [1.42–2.95]). Neither any use, nor >90% adherence to chloroquine/proguanil were protective (adjusted OR for any use 0.57 [0.27–1.21], P=0.14). We concluded mefloquine use was strongly protective against malaria (87% protective efficacy), whereas chloroquine/proguanil, which is no longer recommended but remains widely used, was less than half as effective (43% protective efficacy). Waning efficacy of chloroquine/proguanil may have contributed to the observed increase in malaria among travellers to The Gambia in 2000. Local factors may also influence the risk of malaria. Malaria could be prevented among travellers to West Africa if current national guidelines on antimalarial prophylaxis were better implemented.

When enough quantitative information is available, geostatistics is undoubtedly the best tool for building models of reservoirs that reflect the current level of uncertainty and that can incorporate many different types of data.

OBJECTIVES To assess whether the clinical and laboratory methods for diagnosing Strongyloides stercoralis infection in non-endemic countries is different between those who are chronically exposed and those who travel. METHODS Analysis of laboratory and clinical data from 204 patients having S. stercoralis infection at the Hospital for Tropical Diseases, London. RESULTS Sixty-four travellers and 128 immigrants from endemic countries had laboratory-proven strongyloides. In those with microscopically proven disease, serology was 73% sensitive in travellers and 98% sensitive in immigrants (P < 0.001). There was no difference in the eosinophil count between the two groups with 19% having a normal count. Patterns of symptoms varied between the groups, and around one-third were asymptomatic in both groups. Serology was of limited use in follow-up. CONCLUSIONS Eosinophil count and stool microscopy are insufficiently sensitive to be used alone for screening strongyloides. The sensitivity of serology is good in immigrants with chronic infection, but lower in travellers.

Staying Active—Staying Safe is an initiative of the Northern Sydney Health Promotion unit and the Safe Communities project in Ryde. The aim of the initiative is to develop a resource that promotes exercises that can be completed at home by the more frail members of the older population. The resource consists of an audiotape and a booklet, which facilitate exercise at a pace and at a level of simplicity that is appropriate for this age group. This article describes the development and evaluation of the resource, and considers the ways in which the resource is useful in increasing physical activity, functional mobility, and self-efficacy in completing everyday tasks.

Summary objectives To examine the utility of the different elements of screening expatriates and travellers returned from the tropics for parasitic disease (exposure history, symptoms, examination and laboratory tests). methods In phase 1 (conducted prospectively 1990–91), 1029 asymptomatic returnees had a detailed questionnaire and interview on risk-behaviour, physical examination and laboratory tests. In phase 2 (1997–98), 510 consecutive patients referred for routine screening (276 symptomatic and 234 asymptomatic) were screened with laboratory tests. results Exposure history did not correlate reliably with parasite burden. In phase 1 physical examination revealed 387 abnormalities, only three of which indicated parasitic disease. Schistosomal serology was positive in 11% (CI 9–13) of these asymptomatic cases including patients with light or no reported freshwater exposure. Stool microscopy was positive in 19% (CI 16–22) of cases not correlated with reported eating habits, and eosinophilia was present in 8% (CI 6–10). In phase 2 reported symptoms did not correlate with parasitic disease. Schistosomiasis was present in 15% (CI 13–24) of asymptomatic and 18% (CI 13–22) of symptomatic individuals (OR 1.2 P = 0.46); stool microscopy was positive in 14% of both symptomatic and asymptomatic patients, and eosinophilia in 9% of symptomatic and 6% of asymptomatic individuals. conclusion Potentially serious asymptomatic infection is common in travellers. Detailed exposure history, symptom history and physical examination added little to detecting cases. Stool microscopy, schistosomal serology and eosinophil count all had good yield. Filarial serology had low yield in patients without eosinophilia.

Falls are a common and serious health problem. Responses to the problem should address the individual, the individual's environment, the system of health or residential care used by the individual, and the local community. This article describes a response to the issue of falls in Ryde Hospital and its surrounding community. This response has multiple components which include patient and staff education and interventions with people who have fallen. These initiatives have been developed without additional resources and incorporated into existing systems of care provision.

Aims: MSCs are cells being investigated for use in various therapies including facilitation of HSC transplantation and as gene therapy delivery vehicles. We have explored the potential to increase the number of bone marrow (BM) MSCs in vivo, induce mobilization using various cytokine regimens and improve gene transfer into these cells with adeno-associated virus (AAV) in a baboon model. Method: Baboons received cytokines as follows: 1. G-CSF 100mcg/kg/day for 5 days; 2. pegylated G-CSF (pegG-CSF), single dose 300mcg/kg day −5; 3. G-CSF 100mcg/kg/day + stem cell factor (SCF) 50mcg/kg/day for 5 days; and 4. pegylated megakaryocyte growth and development factor (pegMGDF) 1mcg/kg second daily for 10 days + G-CSF 100mcg/kg/day for 5 days starting day −5. Animals underwent BM aspiration at baseline and on the final day of cytokines along with leukapheresis to isolate PBMNCs for detection of peripheral blood (PB) CFU-F. The immunophenotype and differentiation potential of CFU-F derived from animals before and after cytokines was compared. The ability of AAV vectors pseudotyped with capsids derived from AAV of serotypes 1, 2, 3, 4, 5, 6, and 8 to mediate transduction of baboon and human MSCs was assessed. Results: Augmentation of bone marrow MSCs was observed with all cytokine regimens with the fold-increase compared to baseline as follows: 4.1, 2.1, 7.6 and 11.2 after G-CSF, pegG-CSF, G-CSF+SCF and G-CSF+pegMGDF respectively (see Figure 1). The immunophenotype of MSCs obtained after cytokines was identical to baseline cells as was their differentation potential. CFU-F were not detected in baseline PB however they were detected in 3/5 animals after G-CSF+SCF at a frequency of 0.8 to 1.5/mL, but no other cytokine regimen. A similar pattern of transduction efficiency using AAV was shared by human and baboon MSCs (see Figure 2) using control Ad293 cells. Specifically AAV vectors expressing capsids of serotypes 2, 3 and 5 were most efficient in transducing human and baboon MSCs. Those expressing capsids from serotypes 1, 4, 6, and 8 were much less efficient in transducing MSCs from either species. Baboon MSCs were able to be transduced by about 100-fold more than their human equivalent cells using AAV serotypes 2, 3, and 5. Conclusion: This is the first report of mobilization of primate MSCs and, together with the demonstration of in vivo augmentation and AAV gene transfer, offers increased therapeutic opportunities for their safe application in a burgeoning number of diseases. Figure 1: In vivo Bone Marrow CFU-F Augmentation following cytokines Figure 1:. In vivo Bone Marrow CFU-F Augmentation following cytokines Figure 2: Transduction profile of AAV vectors expressing capsids of various serotypes Figure 2:. Transduction profile of AAV vectors expressing capsids of various serotypes

Rats were maintained on a corn oil diet and treated with d -fenfluramine at doses of 2.5 mg/kg twice a day for 11 days or with 10 mg or 25 mg/kg once a day for 12 days. The lower dose of d -fenfluramine produced no marked changes in body weight and after 11 days of treatment the weights of the rats on average were only 2% lower than the controls. The food intake of these rats was only decreased on the first day. The two higher doses of d -fenfluramine decreased the food consumption for about 3 days but thereafter it was similar to that of the control rats. The body weight of these rats fell on the first day, but after about four days the gain in body weight paralleled rather than approached that of the control rats. Increasing the dose of d -fenfluramine progressively decreased the relative size of the epididymal fat pad. At the end of the treatment period the rats were fed acutely with fructose to increase the circulating concentrations of corticosterone and to stimulate triacylglycerol synthesis. All three doses of d -fenfluramine decreased the concentration of circulating triacylglycerol after fructose feeding. The 10 mg/kg dose also decreased the basal concentration of triacylglycerol. The two higher doses of fenfluramine decreased the rises in the circulating concentrations of corticosterone, glycerol and fatty acids that are produced by fructose feeding. The basal concentrations of these compounds in the absence of fructose feeding were not significantly affected by the 10 mg/kg dose of d -fenfluramine. The possible relationship between the effect of chronic treatment with d -fenfluramine in decreasing a metabolic stress response and lipolysis is discussed relative to its hypotriglyceridaemic action and its effect on body weight-set point. The results demonstrate that d -fenfluramine produced persistent changes in metabolism at a time when the treated rats were growing at the same rate as the control rats and when they were eating similar quantities of food.