[Cytochrome pharmacogenetics applied to the prescription of antidepressants: Instructions for use]. / Pharmacogénétique des cytochromes appliquée à la prescription des antidépresseurs : mode d'emploi.

CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy, and safety of antidepressants. This article is an instruction manual and a guide for the deployment, in hospitals, of pharmacogenetics as an aid to the prescription of an antidepressant. It synthesizes the recommendations of two learned societies, the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG), to produce a recommendation table adapted to a wide panel of antidepressants.

High acquisition rate of extended-spectrum ß-lactamase-producing Enterobacteriaceae among French military personnel on mission abroad, without evidence of inter-individual transmission.

OBJECTIVES: Acquisition of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) by Europeans travelling individually in high-endemicity countries is common. However, how the different ESBL-E strains circulate in groups of travellers has not been studied. We investigated ESBL-E transmission within several groups of French military personnel serving overseas for 4-6 months. METHODS: We conducted a prospective study among French military personnel assigned to Afghanistan, French Guiana or Côte d'Ivoire for 4-6 months. Faecal samples provided by volunteers before leaving and after returning were screened for ESBL-E isolates. ESBL Escherichia coli from each military group was characterized by repetitive element palindromic polymerase chain reaction (rep-PCR) fingerprinting followed, in the Afghanistan group, by whole-genome sequencing (WGS) if similarity was ≥97%. RESULTS: Among the 189 volunteers whose samples were negative before departure, 72 (38%) were positive after return. The highest acquisition rates were observed in the Afghanistan (29/33, 88%) and Côte d'Ivoire (39/80, 49%) groups. Acquisition rates on return from French Guiana were much lower (4/76, 5%). WGS of the 20 strains from the Afghanistan group that clustered by rep-PCR identified differences in sequence type, serotype, resistance genes and plasmid replicons. Moreover, single-nucleotide polymorphism (SNP) differences across acquired strains from a given cluster ranged from 30 to 3641, suggesting absence of direct transmission. CONCLUSIONS: ESBL-E. coli acquisition was common among military personnel posted overseas. Many strains clustered by rep-PCR but differed by WGS and SNP analysis, suggesting acquisition from common external sources rather than direct person-to-person transmission.

[Bisalbuminemia: A case report]. / Les bisalbuminémies : à propos d'un cas.

INTRODUCTION: Bisalbuminemias consist in rare qualitative modifications of several aspects in the albumin pattern. Bisalbuminemias, most of which are not pathological, can be observed using capillary electrophoresis. CASE REPORTS: We report a case of hereditary bisalbuminemia diagnosed by chance while exploring chronic unexplained hypereosinophilia in a 42-year-old patient. The patient's normal lipid profile, the lack of an antibiotic treatment or pancreatic pathology, and the persistence of the bisalbuminemia after one month, suggested a diagnosis of genetic bisalbuminemia. In light of other such cases, we review the main causes of bisalbuminemia, both genetic and acquired. CONCLUSION: The diagnosis of genetic bisalbuminemia is made by first eliminating the usual acquired etiologies: analytical or drug interference, acute pancreatitis and binding of immunoglobulins. Then, after having checked the lipemic index, reviewed the patient's medical history, comorbidities, and treatments, repeating the electrophoresis will help identify the cause of the bisalbuminemia.

Severe rhabdomyolysis induced by quetiapine and mirtazapine in a French military soldier.

Rhabdomyolysis is a potential complication of psychotropic drugs use and may potentially lead to life-threatening complications, such as an acute renal failure. We describe the case of a 40-year-old military soldier suffering from post-traumatic stress disorder was admitted for an adaptation of his treatment. Mirtazapine was introduced and quetiapine increased. Two days later, the patient presented with severe rhabdomyolysis syndrome. Mirtazapine administration was paused and intravenous hydration commenced. Shortly after the creatine kinase levels decreased enabling mirtazapine to be reintroduced without complication. It is our opinion that 5-hydroxytryptamine 2a serotonergic receptors inhibition (related to mirtazapine and quetiapine) associated with muscle training was responsible for inducing rhabdomyolysis. This must be kept in mind when psychotropic medications are adjusted, especially in an athletic population such as military.

Biochemical analysis of cerebrospinal fluid in the laboratories of deployed medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?

INTRODUCTION: During military deployment, the diagnosis and the management of acute bacterial meningitis can be problematic, as deployed Medical Treatment Facilities (MTFs) often have a limited laboratory diagnostic capability. However, French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary (Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard hospital bench top analyser in order to determine if these POC devices have a potential role in the biochemical analysis of cerebrospinal fluid (CSF protein, CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index methods and the reference methods (suitable kits on the Cobas 6 000 System) was evaluated by parallel testing of 30 CSF samples by both techniques. For CSF protein, agreement between the strip and the reference method was evaluated determining the κ coefficient. For CSF glucose and CSF lactate subgroups, least squares linear regressions were calculated and Bland-Altman analyses were performed. RESULTS: The Multistix 10 SG strip can be used to make a semiquantitative determination of CSF protein. A good agreement between the strip and the reference method was observed (κ coefficient: 0.93 (IC95 0.82 to 1)). This strip is thus well adapted to demonstrate an elevation of CSF protein level as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges correlated well with the reference methods for the determination of CSF glucose and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (∼ -7% and ∼ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip and of the iSTAT system appears to be an attractive solution for the biochemical investigation of CSF in medical treatment facilities with limited laboratory diagnostic capability.

[Prolonged neuromuscular block in a patient with butyrylcholinesterase deficiency]. / Curarisation prolongée liée à un déficit en butyrylcholinestérase.

Succinylcholine is a neuromuscular block whose duration of action depends on rapid hydrolysis by butyrylcholinesterase (BChE). In patients with common BChE activities, succinylcholine duration of action is short (10min). BChE deficiency induces a slower hydrolysis of the drug and consequently prolonged neuromuscular block, leading to apnea. We report a case of prolonged neuromuscular block after administration of succinylcholine in a 14-year-old boy. Biological investigations revealed a marked BChE deficiency (1099U/L) related to the presence of three point mutations in the BCHE gene in a compound heterozygous state: p.Asp70Gly (rs1799807), p.Ala539Tyr (rs1803274), and p.Phe118Valfs*12 (rs398124632). The diagnosis of genetic BChE deficiency (OMIM 177400) was retained. This case is intended to present the pathophysiology of genetic BChE deficiency, its management, and the diagnostic strategy to be implemented.

Human butyrylcholinesterase polymorphism: Molecular modeling.

BACKGROUND: Prolonged apnoea following injection of ester-containing myoralaxants was first described in 1953. Because a large part of administered succinylcholine is shortly hydrolyzed by plasma butyrylcholinesterase (BChE) under normal conditions, prolonged apnoea was attributed to deficiency in BChE. It was found that BChE deficiency was due to genetic variations. Human BChE gene shows a large polyallelism. About 75 natural mutations of the BCHE gene have been documented so far [1]. Most of them cause alteration in BChE activity through point mutation effect on catalytic activity. Frame shifts and stop codons may also affect expression, or cause truncations in the sequence. OBJECTIVE: Recently, two novel BChE "silent" variants, Val204Asp [2] and Ala34Val [3], causing prolonged neuromuscular block after administration of mivacurium, were discovered. Mutations were genetically and kinetically characterized. The aim of the current study was to understand how these mutations determine "silent" phenotype. METHODS: Molecular dynamics studies were carried out with NAMD 2.9 software at the Lomonosov supercomputer. Charmm 36 force field was used, periodical boundary conditions, 1 atm pressure, 298 K. 100 ns molecular dynamics runs were performed for the wild-type BChE and its mutants Val204Asp and Ala34Val. RESULTS: Unlike wild-type BChE, which retained its operative catalytic triad through the whole MD simulation, the catalytic triad of mutants was disrupted, making chemical step impossible. Val204Asp mutation leads to reorganization of hydrogen bonding network around the catalytic triad, which in turn increases the distance between catalytic residue main chains. Mutation Ala34Val, located on the protein surface, leads to increased fluctuations in the Ω-loop and subsequent disruption of the gorge structure, including disruption of the catalytic triad and formation of new hydrogen bonds involving catalytic center residues. CONCLUSIONS: Comparative study of the "silent" Ala328Asp mutant and the catalytically active mutant Ala328Cys shows that MD approach can discriminate between the differential effects of point mutations at a same position.

Faecal carriage of extended-spectrum ß-lactamase-producing enterobacteria among soldiers at admission in a French military hospital after aeromedical evacuation from overseas.

The aim of this study was to assess the faecal carriage of carbapenemase-producing enterobacteria (CPE) and extended-spectrum ß-lactamase (ESBL)-producing enterobacteria among soldiers at admission in a French military hospital after aeromedical evacuation from overseas. During a period of 1 year, 83 rectal swabs collected in French soldiers at admission were screened for multidrug-resistant enterobacteria with a chromogenic medium. ESBL detection was performed with the double-disc synergy test in the absence or presence of cloxacillin. The genotypic characterisation of resistance mechanisms, sequence typing and phylotyping was performed by polymerase chain reaction (PCR) and sequencing with bacterial DNA extracted from isolates. No CPE was detected. Eleven ESBL Escherichia coli isolates belonging to four phylogenetic groups were detected, including ten CTX-M-15 and one CTX-M-14. The overall gut colonisation with ESBL-producing bacteria (13.25 %) was 6-fold higher than that reported in soldiers in the suburbs of Paris in 2009. ESBL faecal carriage was particularly high (34.48 %) in soldiers repatriated from Afghanistan (risk ratio = 18.62; p = 0.0001). This study highlights the importance of systematic additional contact precautions and CPE/ESBL screening in soldiers repatriated from overseas in French hospitals.

Abdominal wall and intra-peritoneal abscess by Propionibacterium avidum as a complication of abdominal parietoplasty.

Propionibacteria are organisms of low pathogenicity and only a minority of clinical Propionibacterium isolates is clinically significant. Herein, we report a rare case of Propionibacterium avidum abdominal wall and intra-peritoneal abscess that developed in 46-year-old woman after abdominal parietoplasty.

Recurrent pyelonephritis due to NDM-1 metallo-beta-lactamase producing Pseudomonas aeruginosa in a patient returning from Serbia, France, 2012.

We describe the first isolation in France of a New-Delhi metallo-beta-lactamase-1 (NDM-1) producing Pseudomonas aeruginosa. In March 2012, a patient with history of prior hospitalisation in Serbia was diagnosed in France with acute pyelonephritis due to NDM-1 producing P. aeruginosa. Clinical and microbiological cure was obtained under appropriate antibiotic treatment. Two months later, she presented with a recurrence due to the same bacteria, with a favourable evolution. During both hospitalisations, contact isolation precautions were implemented and no cross-transmission was observed.

Hereditary neuropathy with liability to pressure palsies occurring during military training.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant peripheral neuropathy characterized by recurrent isolated nerve palsies, which are precipitated by trivial compression and trauma. Although HNPP has been well-described in literature, it often goes unrecognized. We report a case of HNPP occurring during military training to promote recognition and proper management of this entity.

[Plasmodium knowlesi: an emerging species in humans?]. / Plasmodium knowlesi: une espèce émergente chez l'homme ?

Plasmodium knowlesi is typically found in macaques and has recently been recognized as the fifth Plasmodium species to cause malaria in humans. Several cases of P. knowlesi malaria have been reported in people in Southeast Asia. Most cases are simple but approximately one in 10 patients develops complications. The morphology of P. knowlesi parasites in human infections closely resembles that of Plasmodium malariae or Plasmodium falciparum, so a molecular method is the optimum diagnostic procedure. The treatment of choice for uncomplicated P. knowlesi malaria is oral chloroquine, whereas severe infection should be treated with intravenous quinine.

[The old man and the syrup]. / Le vieil homme et le sirop.

Intoxication by glycyrrhizin is a rare cause of hypokalemia. We describe a patient with severe hypokalemia caused by long-term consumption of syrup containing liquorice. The physiopathological mechanism of the intoxication and the differential diagnosis are presented.

A travel misadventure--visceral leishmaniasis in an immunocompetent patient.

Visceral leishmaniasis is one of the world's most neglected diseases. Over 90% of the 500,000 annual new cases occur in only five countries: India, Nepal, Bangladesh, Sudan and North-Eastern Brazil, but the disease remains endemic in Southern Europe. We report a case of visceral leishmaniasis in an immunocompetent serviceman after a seven-day stay in the Marseilles region of South-Eastern France. This case is intended to alert clinicians to the possibility of visceral leishmaniasis in patients who develop a febrile illness after returning from travel in Southern European countries.

[Noroviruses: leading cause of gastroenteritis]. / Les norovirus: une cause majeure des gastro-entérites.

Although noroviruses were the first viral agents to be linked to gastrointestinal disease, they were long considered a secondary cause far behind rotaviruses. Development of molecular-based diagnostic techniques has provided clearer insight into the epidemiological impact of noroviruses that are now recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks but also as an important cause of sporadic gastroenteritis in both children and adults. Norovirus infection is generally characterized by mild acute vomiting and diarrhea usually lasting for only a few days, but it can lead to more severe and potentially life-threatening symptoms in high-risk groups such as young children, elderly, and immunodeficient persons. It has been demonstrated that they are present in tropical countries. Molecular epidemiological studies have documented the great genetic diversity of noroviruses with regular emergence of variants. Since no vaccine is available, prevention on norovirus infection depends mainly on strict personal and community hygiene measures.

[Value of assaying adenosine deaminase level in patients with neuromeningeal tuberculosis]. / Intérêt du dosage de l'adénosine désaminase dans les infections tuberculeuses neuro-méningées.

Neuromeningeal tuberculosis is a rare extrapulmonary location in France. Delayed diagnosis can lead to therapeutic failure and severe sequels. However early diagnosis is a major challenge that requires the proper epidemiological, clinical, radiological and biological resources. Problems related to diagnosis of mycobacteria infection and to shortcomings in certain healthcare systems can hinder early diagnosis. The purpose of this review was to describe the diagnostic value of assaying adenosine deaminase activity in cerebrospinal fluid from patients with neuromeningeal tuberculosis. Evidence from studies published over the last 25 years indicate that the sensitivity and specificity of measuring adenosine deaminase activity range from 36 to 92% and 71 to 100% respectively depending of cutoff values used. Before performing this assay, it is necessary to rule out obvious or frequent etiologies such as purulent bacterial meningitis or cryptococcosis in HIV patients. Taken together these studies show that this simple, inexpensive technique is a valuable tool for early diagnosis and management of tuberculosis patients and that it can be easily implemented in hospital labs regardless of technical or financial resources.

[HLA-B*5701 and abacavir hypersensitivity reaction]. / Génotype HLA-B*5701 et hypersensibilité à l'abacavir.

A potentially life-threatening hypersensitive reaction occurs in association with initiation of HIV nucleoside analogue abacavir therapy in 4 to 8% of patients. Preliminary studies appear to confirm the role of the immune system in abacavir hypersensitivity. The reaction is possibly the result of presentation of drug peptides onto HLA, that may induce a pathogenic T-cell response. Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele and prospective HLA-B*5701 genetic screening has now been instituted in clinical practice to reduce the risk of hypersensitivity reaction.

Noroviruses: a challenge for military forces.

For military forces, the control of infectious acute gastroenteritis constitutes an old, constant and unsolved concern. Recent epidemiological studies suggest that the common bacterial causes are being overtaken by viruses. Norviruses are the most alarming group and norovirus outbreaks in military forces are regularly reported. Illness is generally mild and characterised by acute vomiting and diarrhoea, which lasts for a few days on average, but may be severe and potentially life-threatening in subjects who are already dehydrated due to daily activity. Moreover, outbreaks may diminish operational effectiveness. Prevention of norovirus infection currently relies on strict application of personal and collective hygiene rules including isolation of the cases, to the greatest possible extent. Although noroviruses are frequently mentioned as the cause of gastroenteritis outbreaks in troops deployed overseas, laboratory diagnosis is rarely done. So their real burden in military forces remains unclear and further epidemiological studies are required to determine the full impact of norovirus gastroenteritis on troops.

[Impact of rotavirus vaccines in developing countries]. / Impact des vaccins contre les rotavirus dans les pays en développement.

Rotaviruses discovered in 1973 are the most common cause of severe diarrheal disease in infants and young children world-wide. Annually rotavirus infections are estimated to cause the deaths of more than 600,000 children under the age of 5 years with more than 90% of fatalities occurring in developing countries. In 2006 two live oral attenuated rotavirus vaccines were licensed: the monovalent human rotavirus vaccine (RotarixT) and the pentavalent bovine-human, reassortant vaccine (RotaTeqT). Both vaccines demonstrated excellent safety and protective effectiveness in large pre-licensing trials conducted in Europe, the United States and Latin America. Several countries in Latin and Central America have already decided to include rotavirus vaccines into their national immunization program. African and Asiatic countries have postponed their decisions pending the results of further studies.