Concerning one case of rupture of a flow regulator: How patient safety procedures contribute to the correct use of medical devices.

Flow regulators are widely used in hospitals to assist with intravenous (IV) infusion of medication. The rupture of a flow regulator at the base of the clamp was observed during parenteral nutrition. This rupture resulted in fluid leakage and an inlet of air, responsible for an air embolism in a fragile patient who had undergone a bilateral lung transplant. The patient's clinical condition required him to be transferred to a continuous monitoring unit. A serious Adverse Event in Healthcare (AEH) was reported, as well as a medical device vigilance report. A Feedback Committee (FC) was set up and it recommended an audit within the health care departments to study the conditions for use of flow regulators and to propose corrective actions. Despite the technical data sheet of the device not recommending the administration of lipid emulsions and glucose solutions above 10%, the manufacturer's expert report concluded that the mechanical failure could not be linked to the type of solution. However, the audit did reveal a lack of knowledge of certain rules for using this device. The analysis of this AEH is part of the establishment's patient safety procedure. The AEH highlighted a deviation in care concerning the conditions for use of flow regulators, thus resulting in misuse. The collaboration between the various actors involved in the analysis of this AEH led to the implementation of improvement actions on the root causes, related to the lack of information and of training for professionals on correct use of the medical device.

Congenital toxoplasma infection: monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years.

BACKGROUND: Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. METHODS: We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. RESULTS: Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P = .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were <10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and then continued increasing to 52.3% and almost 70% at 28 and 39 GA weeks, respectively. Because of a significant reduction in risk of clinical signs of congenital toxoplasmosis in infected children born from mothers diagnosed after 1995 when polymerase chain reaction testing on amniotic fluid was initiated (87/794 vs 46/1150; P = .012), probabilities of clinical signs at 3 years were estimated based on 1015 maternal infections diagnosed after 1995 including 207 infected children, with symptoms in 46 (22.2%). CONCLUSIONS: These analyses demonstrated that introduction of monthly prenatal screening and improvement in antenatal diagnosis were associated with a significant reduction in the rate of congenital infection and a better outcome at 3 years of age in infected children. Our updated estimates will improve individual management and counseling in areas where genotype II Toxoplasma is predominant.

[Chronic facial ulceration in France and potential involvement of Leishmania infantum cutaneous leishmaniasis]. / Ulcération chronique du visage : penser à une leishmaniose cutanée métropolitaine due à Leishmania infantum.

BACKGROUND: In France, cutaneous leishmaniasis is frequently seen in patients returning from North Africa or South America. Autochthonous leishmaniasis due to Leishmania infantum causes rather visceral forms. Nevertheless, cutaneous leishmaniasis caused by this parasite is occasionally seen in immunocompetent patients who have never been outside France. PATIENTS AND METHODS: An 8-year-old girl living in the Haute-Savoie region and who had never travelled overseas presented with chronic ulceration of the right cheekbone that failed to regress under topical therapy. Laboratory tests demonstrated the presence of L. infantum. Following cryotherapy and intralesional injections of meglumine antimonite, the lesion resolved within a month. The patient's medical history revealed repeated journeys to the Pyrénées-Orientales region of southern France. DISCUSSION: For chronic ulceration on an uncovered area that does not resolve with topical therapy, cutaneous leishmaniasis should be considered in the differential diagnosis even if the patient has never left France. Trips to the South of France (an endemic region) should be sought in the history. In addition to direct examination of the product from curettage of the lesion and histopathology, non-invasive methods such as Western blotting with PCR run on filter paper impressions allow accurate diagnosis.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Methods/Findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/Significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Author's Summary: Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti- T.gondii IgM results for those without IgG antibodies to T.gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T.gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.

[Toxoplasmosis in pregnancy: Practical Management]. / Toxoplasmose pendant la grossesse : proposition actuelle de prise en charge pratique.

The burden of congenital toxoplasmosis has become small in France today, in particular as a result of timely therapy for pregnant women, fetuses and newborns. Thus, the French screening and prevention program has been evaluated and recently confirmed despite a decline over time in the incidence of toxoplasmosis. Serological diagnosis of maternal seroconversion is usually simple but can be difficult when the first trimester test shows the presence of IgM, requiring referral to an expert laboratory. Woman with confirmed seroconversion should be referred quickly to an expert center, which will decide with her on treatment and antenatal diagnosis. Although the level of proof is moderate, there is a body of evidence in favor of active prophylactic prenatal treatment started as early as possible (ideally within 3 weeks of seroconversion) to reduce the risk of maternal-fetal transmission, as well as symptoms in children. The recommended therapies to prevent maternal-fetal transmission are: (1) spiramycin in case of maternal infection before 14 gestational weeks; (2) pyrimethamine and sulfadiazine (P-S) with folinic acid in case of maternal infection at 14 WG or more. Amniocentesis is recommended to guide prenatal and neonatal care. If fetal infection is diagnosed by PCR on amniotic fluid, therapy with P-S should be initiated as early as possible or continued in order reduce the risk of damage to the brain or eyes. Further research is required to validate new approaches to preventing congenital toxoplasmosis.

When are we going to celebrate the centenary of the discovery of efficient treatment for congenital toxoplasmosis?

In 2008, we have celebrated the centenary of the discovery of Toxoplasma gondii.Although this ubiquitous protozoan can generate devastating damage in foetuses and newborns, its treatment is the only field in which we have made little progress, despite a huge body of research, and has not yet been validated. Pregnant women who seroconvert are generally given spiramycine in order to reduce the risk of vertical transmission. However, to date, we have no evidence of the efficacy of this treatment because no randomized controlled trials have as yet been conducted. When foetal contamination is demonstrated, pyrimethamine, in association with sulfadoxine or sulfadiazine, is normally prescribed, but the effectiveness of this treatment remains to be shown. With regard to postnatal treatment, opinions vary considerably in terms of drugs, regimens and length of therapy. Similarly, we do not have clear evidence to support routine antibiotic treatment of acute ocular toxoplasmosis. We must be aware that pregnant women and newborns are currently being given empirically potentially toxic drugs that have no proven benefit. We must make progress in this field through well-designed collaborative studies and by drawing the attention of policy makers to this disastrous and unsustainable situation.

Factors affecting the adherence to an antenatal screening programme: an experience with toxoplasmosis screening in France.

Monthly serological testing is mandatory in France for pregnant women not immune to toxoplasmosis. We assessed for the first time the adherence to this national programme, using data from antenatal tests for Toxoplasma antibodies collected by the Union of Health Insurance Services in the French Rhone-Alpes region.

[Motivations for a consultation before adoption: A multicenter study]. / Étude multicentrique sur les motivations d'une consultation avant adoption.

INTRODUCTION: While the number of international adoptions in France is decreasing, adopted children are older and in poorer health than they used to be. This phenomenon has resulted in an increase in the demand for preadoption consultations over the past several years. This study analyses the reasons for these consultations. METHOD: Prospective multicenter study conducted from 1 January to 31 December 2013. RESULTS: Ten centers contributed to the study, i.e., 196 preadoption consultations. Seeking medical advice was the reason for 88% of the consultations, whether the advice was based on the study of an identified child's medical file (32%) or a country's healthcare characteristics, whether the country was identified (34%) or not (23%). In 6% of cases, the motive for preadoption consultations was social and familial, and in the last 5% it was to obtain general information about adoption and its procedures. In more than 40% of the cases, whether the child or the country identified, Russia is the subject of the consultation because of the complexity of the files and because of the dreaded but rarely mentioned fetal alcohol syndrome. CONCLUSION: The deterioration of adopted children's health is an additional worry for future adoption applicants. To provide them with the best information possible without making choices for them, specialists should have substantial experience in adoption before going into these preadoption consultations.

Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana.

Vivax malaria is widespread and resistance has been described for chloroquine and sulfadoxine-pyrimethamine. We report on evidence of failure of mefloquine prophylaxis in a French soldier who contracted Plasmodium vivax in French Guyana, South America. Despite regular weekly mefloquine prophylaxis (250 mg/d), the patient presented with a first episode of vivax malaria, which was treated by chloroquine alone, then experienced a second crisis in France. The reappearance of the parasites occurred one day after the end of prophylaxis, confirming parasitological and clinical resistance in a non-immune patient. Mefloquine was detected by a liquid chromatography assay in plasma at a level of 1062 ng/ml, which was higher than the expected concentration after five months of weekly prophylaxis. This isolate had no single nucleotide polymorphisms of the pvmdr1 gene at seven allele positions: pvmdr1 N91, Y189, Y976, S1071, F1076, N1079 and D1291, corresponding to codons 86, 184, 939, 1034, 1039, 1042 and 1246 in P. falciparum. This observation of failure of mefloquine prophylaxis against P. vivax, when added to previously reported chloroquine and atovaquone-proguanil failure, strengthens the case for re-evaluating drug policies for vivax malaria and the need for continuous research on molecular markers of drug resistance.

PMP-22 expression in the central nervous system of the embryonic mouse defines potential transverse segments and longitudinal columns.

PMP-22, a major constituent of peripheral nervous system (PNS) myelin, is also present in the central nervous system (CNS), in motoneurons of the cranial nerve motor nuclei and spinal cord (Parmantier et al. [1995] Eur. J. Neurosci. 7:1080-1088). The expression of PMP-22 in the CNS during embryonic and early postnatal development was investigated and showed a biphasic spatio-temporal pattern. The expression of PMP-22 started at embryonic day (E)11.5, in restricted longitudinal and transverse domains, in the ventricular zone of the spinal cord, rhombencephalon, mesencephalon and prosencephalon. In the mid- and forebrain, the PMP-22 signal was detectable in a longitudinal domain that followed ventrally the basal/alar boundary but could no longer be detected dorsally at some distance from the roof plate. Along the caudo-rostral axis, the territory in which PMP-22 was detected spanned the mesencephalon and the prosencephalon, extending caudally from the limit between the isthmus and the mesencephalon, and rostrally to the boundary between prosomeres 4 and 5 (p4/p5). In agreement with the prosomeric model of forebrain organization proposed by Puelles and Rubenstein ([1993] TINS 16:472-479), differences in the level of PMP-22 expression in p2, p3, and p4 clearly defined the p2/p3 and p3/p4 neuromeric boundaries. By E17.5, PMP-22 was no longer detected in the ventricular zone, but at E18.5 it began to be expressed in motoneurons of cranial nerve motor nuclei and, after birth, following a rostro-caudal gradient, in the ventral spinal cord.

Evidence of cerebrospinal fluid free kappa light chains in AIDS patients with Toxoplasma gondii encephalitis.

Cerebrospinal fluid (CSF) free light chains of kappa or lambda (FLC kappa/lambda) type were investigated by affinity mediated blotting technique (AMI) and ELISA in 28 patients of which nine with AIDS and Toxoplasma gondii encephalitis (AIDS, TE), 11 with AIDS with or without other CNS AIDS-related opportunistic infections (non-TE AIDS) and eight control patients with or without inflammatory neurological disorders (control group). CSF restricted oligoclonal FLC bands either of k or lambda isotype or both were found by AMI in 18 (90%) out of 20 AIDS patients, while a CSF pattern predominantly characterized by FkappaLC rather than FlambdaLC was observed in eight (88.8%) out of nine TE patients. No FLC components were detected in the matched sera of TE or non-TE AIDS patients or in the CSF and sera from control group. The anti-parasite-specific FkappaLC CSF/serum mean levels and the T. gondii-specific FkappaLC index values were found by ELISA to be significantly more elevated in TE patients when compared to non-TE AIDS or control group. These findings suggest that the increased production of T. gondii-specific FkappaLC could provide insights into pathogenesis of reactivated TE in immunocompromised patients and may have important diagnostic usefulness.

Advanced laboratory techniques for diagnosing Toxoplasma gondii encephalitis in AIDS patients: significance of intrathecal production and comparison with PCR and ECL-western blotting.

The polymerase chain reaction (PCR) for detection of cerebral spinal fluid (CSF) Toxoplasma gondii DNA was combined with the study of intrathecal antibody synthesis by antibody specific index calculation (ASI) and the detection of specific oligoclonal IgG bands (OCB) by affinity mediated immunoblotting (AMI) in 11 AIDS patients with T. gondii encephalitis (TE) and in 20 control patients with or without neurological disorders. Enhanced chemiluminescence (ECL) western-blot technique was employed to evaluate the antigenic specificity of CSF-IgG towards individual T. gondii antigens. PCR was positive in all TE patients which displayed brain-derived or blood-derived specific OCB, even when comparative ASI failed. Four TE patients had a unique anti-T. gondii OCB restricted to the CSF and a strong antibody response toward the 29 kDa band by ECL western blot. This response could be an important marker to discriminate TE from other opportunistic central nervous system (CNS) infections in the course of AIDS.

Monocyte tissue factor expression induced by Plasmodium falciparum-infected erythrocytes.

Monocytes are active elements of the host response against Plasmodium falciparum. They are able to express tissue factor and trigger the extrinsic pathway of blood coagulation the activation of which remained unclear in malaria. Our aim was to assess the tissue factor expression of purified blood monocytes stimulated by cultured Plasmodium falciparum-infected erythrocytes. Malaria parasite induced an early generation of tissue factor with a peak between 8 and 12 h of stimulation. Maximum expression was observed for parasitemia ranging from 1 to 2%. Plasmodium falciparum culture supernatants had the same effect showing the existence of a soluble factor able to induce the tissue factor expression. These data, demonstrating an activation of the tissue factor pathway by the malaria parasite, emphasize thrombin generation. Therefore, thrombin could participate in malaria pathology either in the microcirculatory blockade via platelet and fibrinogen activation or as a mitotic.

Relationships between clinical protection and antibodies to Plasmodium falciparum RESA (ring-infected erythrocyte surface antigen) peptides.

A longitudinal study involving 76 individuals living in Dafinso and Vallée du Kou (near Bobo-Dioulasso, Burkina Faso, West Africa) was performed in June 1987 (beginning of the transmission period), August-September 1987 (during) and January 1988 (after). The serological antibody (Ab) responses against synthetic peptides representing repeat amino acid sequences of the P. falciparum Ring-Infected Erythrocyte Surface Antigen (RESA): (EENV)5, (EENVEHDA)4, (DDEHVEEPTVA)2 were evaluated by ELISA. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of age and occurrence of clinical malarial attack (greater than 5000 parasites mm-3 of blood and axillary fever greater than 37.7 degrees C). Levels (A620) of Ab to (EENVEHDA)4 and (DDEHVEEPTVA)2 were correlated with age. The adult group (III) had the highest prevalences of Ab to RESA peptides. No significant difference was found between groups of children with or without malaria attack. Nevertheless, at the beginning of the transmission period, children who had at least one malaria attack during the study presented the lowest level of antibodies to RESA peptides.

Correlation between beta 2-microglobulin and soluble interleukin-2 receptor levels in plasma of individuals living in a malarial endemic region.

beta 2-Microglobulin (beta 2m) levels were related to the expected immunoprotection in 81 individuals living in a malarial mesoendemic area near Bobo-Dioulasso (Burkina Faso), who were longitudinally followed. Soluble interleukin-2 receptor (sIL-2R) levels were positively correlated to those of beta 2m (r = 0.44; n = 237; P less than 0.001). This suggests that most of the beta 2m could have originated from activated T and B cell membrane turnover. In our study, both beta 2m and sIL-2R were inversely related to IgG antibodies (Ab) against somatic antigen of Plasmodium falciparum (Som-Ag). Therefore, these molecules at high levels could have a down regulating activity, directly or indirectly, on B cells producing this kind of Ab.

Value of cerebrospinal fluid cytochemical examination for the diagnosis of congenital toxoplasmosis at birth in France.

BACKGROUND: Because of routine screening and treatment of pregnant women for Toxoplasma infection in France, most neonates born to mothers who seroconverted during pregnancy are either not infected or asymptomatic. Early diagnosis relies mainly on radiologic, ophthalmologic and biologic tests. Cerebrospinal fluid (CSF) cytochemical evaluation is one of several tests performed in parallel to increase the overall sensitivity of the diagnostic evaluation. Our goal was to assess the value of cytochemical examination and to confirm whether using a portion of available CSF for this analysis is legitimate. METHODS: The individual performance of each of the two cytochemical tests and their combined value when used in parallel were assessed. These findings were then compared with the anti-Toxoplasma IgM and IgA serum titers and the clinical, ophthalmologic and radiologic findings at birth. RESULTS: CSF cytochemical analysis was possible in only 52% of the 233 children in the study. Our results in 112 children indicated poor sensitivity estimates. There was no significant change in the posttest probability of infection compared with the pretest estimation of risk in cases of a negative finding. After a mean follow-up of 80 months there was no evidence that CSF cytochemistry helped predict the risk of sequelae. CONCLUSION: In our setting cytochemical examination did not significantly contribute to the diagnosis of congenital infection at birth. Because of the limited quantity of CSF available, we suggest the use of other methods with higher yield.

Effect of prenatal treatment on mother to child transmission of Toxoplasma gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.

BACKGROUND: The aim of prenatal serological screening for toxoplasmosis is to identify and treat maternal infection as soon as possible in order to prevent transmission of the parasite to the fetus. However, despite widespread provision of prenatal toxoplasma screening across Europe, the effectiveness of prenatal treatment is uncertain. The study aimed to determine the effect of the timing and type of prenatal treatment on mother to child transmission of Toxoplasma gondii. METHOD: A cohort of 554 infected pregnant women were identified in Lyon, France between 1987 and 1995 and their children were followed to determine congenital infection status. We determined the effect of prenatal treatment on transmission by examining the effect of the delay between maternal seroconversion and start of treatment. We also compared the effect of the type of treatment and no treatment on the risk of mother to child transmission. Analyses were adjusted for gestation at maternal seroconversion. RESULTS: Compared to treatment within 4 weeks from seroconversion, the adjusted odds ratios (OR) for mother to child transmission after a treatment delay of 4-7 weeks was 1.29 (95% CI : 0.61, 2.73) and after more than 8 weeks, 1.44 (95% CI : 0.60, 3.31). The adjusted OR associated with spiramycin alone compared with pyrimethamine-sulfadiazine treatment was 0.91 (95% CI : 0.45, 1.84) and the OR for no treatment compared with pyrimethamine-sulfadiazine treatment was 1.06 (95% CI : 0.37, 3.03). CONCLUSIONS: The authors hypothesize that the absence of an effect of prenatal treatment is due to transmission before the start of treatment.

Prenatal diagnosis using polymerase chain reaction on amniotic fluid for congenital toxoplasmosis.

OBJECTIVE: To evaluate sensitivity, specificity, and predictive values of a prenatal amniotic fluid (AF) polymerase chain reaction (PCR) test for diagnosis of congenital toxoplasmosis. METHODS: A multicenter prospective study was done on 271 women with proved primary Toxoplasma infection during pregnancy and who had amniocentesis for prenatal diagnosis by PCR. Live-born infants were eligible for analysis only if a serologic follow-up could assess a definitive infection status. RESULTS: Of the 270 evaluable cases, 75 were congenitally infected, 48 of whom had a positive PCR at prenatal diagnosis. Overall sensitivity of PCR on AF was estimated at 64% (95% confidence interval [CI] 53.1%, 74.9%), negative predictive value of 87.8% (95% CI 83.5%, 92.1%), whereas specificity and positive predictive value were 100% (95% CIs 98%, 100% and 92.3%, 100%, respectively). Among cases with congenital toxoplasmosis, there were no significant differences between those with positive or negative PCR with regard to median gestational age at maternal infection, interval between maternal infection and amniocentesis, or duration of treatment before amniocentesis. However, sensitivity of PCR was found to be significantly higher for maternal infections that occurred between 17 and 21 weeks' gestation (P <.02). CONCLUSION: A negative PCR of AF cannot rule out congenital infection. In this case, continuation of treatment with spiramycin combined with ultrasonographic follow-up and postnatal follow-up are warranted. Our results also suggest presumptive treatment combining pyrimethamine and sulfonamides in case of maternal infection occurring late in pregnancy.