Cytokine profiles in adults with imported malaria.

The increase in worldwide travel is making imported malaria a growing health concern in non-endemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. This study aimed at deciphering the relationship between cytokine host response and malaria severity among imported cases in France. This study reports cytokine profiles in adults with Plasmodium falciparum malaria included in the PALUREA prospective study conducted between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex® technology: interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1α, IL-1ß, IL-2, IL-4, IFNγ, and TNFα, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R = 0.32 [0.16-0.46]; P = 0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Persisting high IL-10 concentration was associated with subsequent nosocomial infection, suggesting its possible interest in immune monitoring of most severe patients.

Outpatient healthcare and clinical trials in the care pathway: Organisational and regulatory aspects and tools.

Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay.

Reasons for seeking care and adherence to pretravel preparation in expatriate or long-term travelers' children in the tropics: A French prospective study.

BACKGROUND: Studies on pediatric travelers' health rarely address expat or long-term travelers' children. METHOD: To investigate reasons for seeking care and adherence to pretravel preparation, we prospectively enrolled French children 0-15 years old, either expatriates or staying >6 months in tropical areas, who attended a French health center in Africa, Central America or Southern Pacific regions from October 01, 2011 to October 31, 2012. A standardized questionnaire was completed by a general practitioner at each visit, then anonymized and included in our database. RESULTS: 464 questionnaires were collected from 367 children (sex ratio M/F: 1:1). Median age was 6.4 years (IQR: 3.6; 10.3). Reasons for seeking care were mostly infections (n = 378), of which 12 (3.2%) were tropical. There were no deaths, but one child with tuberculosis was repatriated. Coverage was high for routine immunization, but less for travel-related vaccines. Personal antivectorial protection was significantly lower in children aged >5 y or in non-malarial areas. Where indicated, malarial chemoprophylaxis was prescribed to only one third of the children, of whom 60% were poorly compliant. Advice regarding measures against diarrhea was followed significantly more for stays <2 yrs. CONCLUSION: Mild cosmopolitan illnesses predominated but protection against tropical threats should be optimized before and during the stay.

Epidemiology of Early-onset Bacterial Neonatal Infections in Madagascar.

BACKGROUND: Little is known about early-onset neonatal bacterial infections (EONBI) in Madagascar. Our aim was to determine their epidemiology to improve their management. METHODS: Inborn neonates at risk for EONBI and admitted in the neonatal unit of 2 tertiary hospitals in Antananarivo, Madagascar, were included in a prospective study from April 2012 to March 2013. Using a clinical algorithm, blood culture, gastric fluid culture and C-reactive protein dosage were performed in newborns at high risk of infection, that is, peri partum fever, prematurity <35 weeks' gestation or birth weight <2000 g, or presenting with clinical signs of infection. EONBI was defined as a bacteremia occurring within the first week of life. RESULTS: Among 307 neonates, 75 (24.4%) had an EONBI caused by 1 (n = 59) or 2 (n = 16) bacteria (91 isolates). Gram-negative bacteria were predominant (n = 62, 82.7%), including Enterobacter cloacae (n = 26), Klebsiella pneumoniae (n = 14), Escherichia coli (n = 7) and Proteus mirabilis (n = 2). Group B Streptococcus, Acinetobacter baumanii and Enterococcus sp. represented 3.6%, 8.2% and 12.1% of the isolates, respectively. All E. cloacae and 12/14 (85.7%) K. pneumoniae were extended-spectrum ß-lactamase producers. At all, 41/91 (45.1%) bacteria were multidrug-resistant (MDR) and 34/75 (45.3%) newborns had an EONBI caused by an MDR bacteria. Neonatal asphyxia was the only factor associated with multidrug resistance (odds ratio: 4.52; CI: 1.20-16.94; P = 0.025). The EONBI-related mortality (n = 20/75, 26.7%) rose up to 38.2% (n = 13/34) in case of MDR bacteria. CONCLUSIONS: The epidemiology of EONBIs in Madagascar is comparable to that found in many low-income countries. Prevention, including improvement of hygiene during resuscitation for neonatal asphyxia, is likely to be more effective in reducing EONBI-related morbidity and mortality than using new antibiotics to counter resistance.

Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism: comment.

Kuperman et al. found that patients with anemia had a higher risk of major bleeding (RR 2.84; 95% CI 2.52-3.39) in RIETE database. Anemia appeared to be an independent predictive factor for major bleeding [hazard ratio (HR) 1.95; 95% CI 1.72-2.20] in this registry. Unfortunately, selection bias due to enrolled patients does not allowed us to use these major results in ambulatory care. The aim of SCORE study was to refine bleeding risk estimation in French vitamin K antagonist (VKA) treated patients and to identifying one or several parameters of prognostic significance. We conducted a prospective, multi-center cohort study of 962 consecutive outpatients from private angiologic offices, clinics and hospitals enrolled in grenoble angiologic network for thromboembolic diseases between May 2009 and December 2010, followed during 1 year by their general practitioner. Main outcome was the occurrence of major bleeding or clinically non major relevant bleeding (CNMRB). Incidence rates major bleeding and CNMRB were 2.86 (95% CI 1.95-4.2) events per 100 patient-years and 12% (95% CI 9.89-14.11) respectively. Cox multivariate analyses showed that only anemia was strongly associated with a risk of major bleeding (HR 6.1; 95% CI 2.7-13.8; p = 0.001). Logistic regression analyses performed in CNMRB showed that anemia, prior gastro-intestinal bleeding and antiplatelet drug use were strongly associated with a risk of CNMRB at 1 year, respectively OR 2.53, 95% CI (1.4-4.56); p = 0.002, OR 3.32, 95% CI (1.51-7.31); p = 0.003 and OR 1.77, 95% CI (1.1-2.83); p = 0.017. These new data were consistent between major and CRNM bleeding in VKA treated patients. The key role of anemia should be confirmed in other prospective cohort studies, with different anticoagulants use such as direct oral anticoagulant in ambulatory care settings.

Severe imported malaria in children in France. A national retrospective study from 1996 to 2005.

BACKGROUNDS: Malaria is a leading cause of imported febrile illnesses in pediatric travelers, but few studies have addressed severe imported pediatric malaria. We aimed to determine the risk factors and the features of imported pediatric severe malaria. METHODS: We conducted a retrospective, descriptive study using the French National Reference Center for Imported Malaria database, in children aged 0-15 years who were hospitalized with a falciparum malaria from January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of falciparum malaria were compared to identify risk factors for severe cases. In the hospitals that reported more than five severe cases during the study period, we evaluated severe cases for prognostic factors and assessed the accuracy WHO criteria for predicting severity. Given the rarity of deaths, adverse outcomes were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation, mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis, fluid resuscitation-or pediatric intensive care unit (PICU) admission. RESULTS: Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated and 851 (20.5%) were severe. Only one death was recorded during this period. Predictors for severe falciparum malaria were: age <2 years (OR = 3.2, 95% CI = 2.5-4.0, p <0.0001) and a travel in the Sahelian region (OR = 1.7, 95% CI = 1.3-2.0, p = 0.0001). Of 422 severe malaria cases, a stay in a Sahelian region, lack of chemoprophylaxis, age <2 years or thrombocytopenia <100 x 10^3/mm^3 predicted adverse outcomes. Except for the hyperparasitemia threshold of 4%, the main WHO 2000 criteria for severe malaria reliably predicted adverse outcomes. In our study, the threshold of parasitemia most predictive of a poor outcome was 8%. CONCLUSION: In imported pediatric malaria, children younger than 2 years deserve particular attention. The main WHO 2000 criteria for severity are accurate, except for the threshold of hyperparasitemia, which should be revised.

Prevalence of Mycoplasma pneumoniae Infection in Malagasy Children.

BACKGROUND: Childhood community-acquired pneumonia is a leading cause of childhood morbidity in low-income countries. The etiologic agents are usually Staphylococcus aureus, Streptococcus pneumoniae and Mycoplasma pneumoniae. M. pneumoniae was recognized as a cofactor in asthmatic disease. High asthma prevalence was reported in Madagascar. Our aim was to clarify the prevalence of M. pneumoniae infection in this country and its relationship with asthma. METHODS: A prospective study was conducted in 351 children (from 2 to 16 years of age) from January 2012 to December 2014. According to the clinical symptoms, children were enrolled in 3 groups: "control group" (CG, n = 106), "asthma group" (n = 129) and "pneumonia group" (n = 116). The IgG and IgM M. pneumoniae status was evaluated by an enzyme-linked immunosorbent assay. Clinical signs of infection, socioeconomic data and antimicrobial treatment were recorded. RESULTS: The overall prevalence of M. pneumoniae infection was 18.2%. The multivariate analysis demonstrated that M. pneumoniae infection was significantly more frequent in the CG [pneumonia group vs. CG: odds ratio = 0.45 (0.21-0.91), P = 0.037 and asthma group vs. CG: odds ratio = 0.39 (0.18-0.87), P = 0.021]. The C-reactive protein value was significantly higher in children with M. pneumonia-positive serology (85 vs. 61 mg/L, P = 0.03). Of note, 99 (41%) children received antibiotics before attending. CONCLUSIONS: We report a prevalence of 18.2% for M. pneumoniae infection in children in Madagascar. The prevalence of M. pneumoniae infection was higher in the control patients than in asthmatic ones.

Barriers to and promoters of screening for falls in elderly community-dwelling patients by general practitioners: a large cross-sectional survey in two areas of France.

The objective was to determine the factors affecting French GPs' implementation of annual screening for falls among patients of 75 years old and over. We conduct a cross-sectional study in two areas in the South-east of France (Savoie and Isère). An anonymized survey was sent by e-mail and/or post in May 2008 to all GPs with a large practice. Reminder letters were sent to GPs who hadn't answered between June and July 2008. Potentials barriers were measured by dichotomous scale. On GPs characteristics (socio-demographic, knowledge, attitude and practice), a multiple logistic regression was performed to identify others factors affecting falls screening. 493 questionnaires were analyzed (26.8%). 65.3% of respondents considered annual screening for falls to be useful, though only 28.8% of them implemented it each year and 9.3% every two to five years. Barriers to achieving annual screening included patient selecting (56.3%), forgetting to screen (26.6%), unsuitable working conditions (18.5%), lack of time (13.3%), of knowledge (13.3%), or of financial compensation (11.1%). Perception of the usefulness of annual screening for falls (OR=5.38 (2.07-14.08); p=0.001), satisfaction with medical care for falls (OR=1.34 (1.09-1.65); p=0.006) and increased consultation time (OR=2.65 (1.37-5.13); p=0.004), were found to have a significant impact on the implementation of annual screening for falls. Asking your patient each year if s/he has had any falls, inquiring about gait and balance disturbance is not time consuming. Finally, to improve a health-related quality of life, GPs should consider fall assessment as a fundamental feature of medical care.

Evaluation of a mobile electronic assistant to aid in fluindione prescription: the INRPlus cluster randomized trial.

INTRODUCTION: Regular monitoring of the international normalized ratio (INR) is crucial for dose adjustment of vitamin K antagonists (VKA) to maximize time in therapeutic range (TTR). We compared the use of a mobile electronic assistant INRPlus which proposes patient-specific fluindione doses, to standard fluindione management in a cluster randomized controlled study. PATIENTS AND METHODS: Twenty clusters of six general practitioners were randomized to adjust fluindione doses in VKA-treated patients either using INRPlus or according to routine practice. TTR was measured over 6 months, along with time spent above or below the recommended INR range, frequency of measurements and related complications. RESULTS: Of the 595 included patients, 551 were assessable (259 INRPlus, 292 control) and had a mean of 1.6 INR measurements/month. TTR was not significantly different between the two groups, 72.7% [Q1: 58.1%; Q3: 90%] in INRPlus patients and 71.2% [Q1: 54.8%; Q3: 88.2%] in control patients (p=0.445). At least 60% time within reference ranges was reported in 73.4% of INRPlus patients and 67.1% of control patients (relative risk 1.09, 95%CI 0.98-1.22, p=0.115). No significant differences were reported between the two groups for time outside reference ranges, frequency of measurements or complications. Eighty-two percent (82%) of patients complying with INRPlus-proposed doses spent more than 60% of TTR versus 66.9% of non-compliant patients and 67.1% of reference patients. CONCLUSIONS: In this trial, the use of the INRPlus electronic assistant resulted in a non-significant improvement in TTR that may be due to a higher than expected TTR in the control group.

Factors affecting dementia screening by general practitioners in community-dwelling elderly populations: a large cross-sectional study in 2 areas of France.

In patients aged 75 years and above, dementia is associated with increased expenditure and high morbimortality. Although the incidence of dementia is well known, it is often underrecognized in primary care. We conducted a cross-sectional study in 2 areas in the southeast of France to identify the factors affecting dementia-screening implementation by the French general practitioners (GPs). In May 2008, an anonymized survey was sent by e-mail and/or post to all GPs with a large clinic practice. Two months later, reminder letters were sent. Overall, 493 GPs answered (26.8%) to self-reported behavior. Of these, 73.2% felt that annual screening was useful, although only 24.5% implemented it each year and 17.5% implemented it every 2 to 5 years. Factors that favorably influenced screening practices were: the older age of the GPs; belief in the usefulness of annual dementia screening; increased frequency of follow-up visits by elderly patients; and the proportion of dementia in the GP's practice. The main barrier to annual screening was the social problems encountered in the medical care of 75-year-old patients. Regardless of the differences in European national health policies or health care systems, all GPs encounter the same difficulties when dealing with elderly dementia patients.

Envenomation by Bothrops atrox in a traveler to Manaus, Brazil.

Snakebites are an infrequent but real risk for travelers. We report a case of envenomation by Bothrops atrox in a traveler to Manaus, Brazil. Rapid administration of specific antivenom prevented the expected systemic disorders. This case gives opportunity to review prevention and first aid measures of snakebites in travelers.

Shigella flexneri bacteremia in two immune-competent adult travelers.

Shigella bacteremias are uncommon in immune-competent adults. We report two cases of Shigella flexneri bacteremia that occurred in healthy young travelers, who recovered. Self-medication with loperamide and ibuprofen without antibiotics (case 1) and concomitant falciparum malaria (case 2) were the only co-morbidities found in our two patients.

Aetiology and epidemiology of fever in children presenting to the emergency department of a French paediatric tertiary care centre after international travel.

OBJECTIVE: As few data are available on the causes of fever in children returning from international travel, the authors studied children presenting to a French tertiary care centre with fever. METHODS: Children presenting to the emergency department of the Robert Debré Paediatric Hospital, Paris, France between July and December 2007 with fever that occurred within 3 months of a stay abroad were included in this retrospective study. RESULTS: The children (n=538) had most commonly visited North Africa (NA) (n=214), sub-Saharan Africa (SSA) (n=185) and Europe (n=67). Their median age was 2.8 years (IQR 1.4-5.8). The median time between their return to France and the onset of fever was 5 days (IQR 0-18). Cosmopolitan infections represented 85% of the established diagnoses (97.8% and 63.9% in the children returning from NA and SSA, respectively). Fever of unknown origin accounted for 19.3% of cases. Malaria was the leading tropical infection. Excluding malaria, diarrhoeal diseases were more frequent in the children returning from NA (38.5%) than in those returning from SSA (24.5%). Malaria was associated with stays in endemic countries that exceeded 30 days (OR 3.13, 95% CI 1.02 to 9.59). CONCLUSION: Cosmopolitan infections are the leading cause of fever in French children returning from tropical and subtropical areas. However, all febrile children who have returned from an endemic area should be tested for malaria.

Doxycycline failure in lymphogranuloma venereum.

Lymphogranuloma venereum (LGV) cases are currently re-emerging in the homosexual community, particularly in HIV-seropositive patients. The standard treatment for this infection, which is caused by Chlamydia trachomatis L1, L2 and L3 serotypes, is a 3-week doxycycline regimen. The case is reported of a male patient presenting with LGV, who was rapidly cured with moxifloxacin treatment after failure of extended treatment with cyclines. This fluoroquinolone is known to be highly active in vitro on the LGV pathogenic agent. Thus it may be a useful alternative when doxycycline treatment results in failure.

Scalp eschar and neck lymphadenopathy caused by Bartonella henselae after Tick Bite.

Rickettsia slovaca and Rickettsia raoultii have been associated with a syndrome characterized by scalp eschar and neck lymphadenopathy following tick bites. However, in many cases, the causative agent remains undetermined. We report 3 cases of this syndrome caused by Bartonella henselae, and we propose the term "SENLAT" to collectively describe this clinical entity.

Travel-related cerebro-meningeal infections: the 8-year experience of a French infectious diseases unit.

BACKGROUND: The etiological spectrum of cerebro-meningeal infections (CMI) in travelers has never been specifically analyzed. OBJECTIVES: To assess the etiologies of CMI in hospitalized travelers and to propose a diagnostic approach to travel-related CMI. METHODS: During an 8-year period, we retrospectively collected data on all travelers hospitalized in our department for a CMI occurring during travel or in the month after their return. RESULTS: Fifty-six patients (35 men and 21 women; mean age 29 years (16-83); 44.6% tourists, 26.8% military, 16% immigrants, 12.5% expatriates) were included. The main destinations were Africa (57.2%), Europe (19.5%), and Asia (12.5%). The median duration of travel was 24 days (5-550). Symptoms occurred during travel in 20 patients (11 of which required a medical evacuation). In the remaining 36 patients, the median duration between return and clinical onset was 10 days. The median time from clinical onset to hospitalization was 4 days (0.5-96). Twenty-four patients presented with a meningeal syndrome and 20 others with encephalitic features. The remaining 12 patients had an incomplete clinical presentation (headaches or fever). The etiology was confirmed in 42 cases (75%) of which tropical diseases (n = 14) were less common than cosmopolitan ones (n = 28). Sub-Saharan Plasmodium falciparum malaria (n = 12) was the leading tropical infection, whereas viral infections (enterovirus, herpesviridae, HIV) were the main cosmopolitan etiologies. Only four bacterial infections were reported (Neisseria meningitidis, Mycoplasma pneumoniae, Brucella melitensis, Salmonella typhi). Sixteen patients were admitted to intensive care for a median time of 9.5 days (1-63). The average duration of hospitalization was 14 days (3-63). One death by herpes simplex virus 1 encephalitis was recorded. Four patients (7%) had neurological sequelae. CONCLUSIONS: Among the diversified etiological spectrum of CMI, cosmopolitan infections are widely predominant, particularly viral infections, followed by tropical causes, of which malaria is the leading disease in returnees from endemic areas. The diagnostic approach should be driven by history and physical examination. Key investigations include: blood smear, cerebrospinal fluid polymerase chain reaction and culture as well as neuroimaging. Management should focus on curable causes.