Pasteur Institute of Morocco

Casablanca, Morocco

Pasteur Institute of Morocco

Casablanca, Morocco
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Gaze W.H.,University of Exeter | Krone S.M.,University of Idaho | Joakim Larsson D.G.,Gothenburg University | Li X.-Z.,Health Canada | And 8 more authors.
Emerging Infectious Diseases | Year: 2013

The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non-disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue.


Malih I.,Pasteur Institute of Morocco | Malih I.,Monash University | Malih I.,Hassan II University Mohammedia - Casablanca | Ahmad rusmili M.R.,Monash University | And 4 more authors.
Journal of Proteomics | Year: 2014

The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity. Biological significance: Naja haje legionis is one of the medically important snakes implicated in the pathogenesis of snake bite in Morocco. The absence of information about venom composition and clinical manifestations of envenomation by this cobra represents an obstacle for the management of this environmental disease in the country. The elucidation of Moroccan cobra venom composition will provide a reasonable guidance for clinician to understand the pathophysiological conditions associated with cobra envenomation and the elaboration of better management strategies. © 2013 Elsevier B.V.


Anwar W.A.,Ain Shams University | Khyatti M.,Pasteur Institute of Morocco | Hemminki K.,German Cancer Research Center | Hemminki K.,Lund University
European Journal of Public Health | Year: 2014

Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease. © 2014 The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.


Barguigua A.,Pasteur Institute of Morocco | Barguigua A.,Chouaïb Doukkali University | El Otmani F.,Chouaïb Doukkali University | Talmi M.,Chouaïb Doukkali University | And 2 more authors.
Microbial Pathogenesis | Year: 2013

This study was designed to characterize extended-spectrum-β-lactamases (ESBL) produced by Escherichia coli isolates causing community urinary tract infections over a 2-year period (2010 and 2011) in a Moroccan large geographical region. Molecular characterization was done by using PCR and sequencing of the β-lactamases genes and plasmid-mediated quinolone resistance determinants. Among 1174 isolates, 49 (4.1%) were ESBL producers. The blaCTx-M-15 (n=31) was the most frequent ESBL gene detected, followed by blaCTx-M-1 (n=5), blaSHV-12 (n=6), blaPER-2 (n=3), then blaTEM-3, blaTEM-20, blaTEM-158, blaSHV-27, blaSHV-28, blaSHV-36, blaSHV-125, blaCTx-M-14 and blaCTx-M-27 with one isolate for each. The non-ESBL genes detected were blaTEM-70 (n=1), blaTEM-176 (n=1), blaTEM-104 (n=6), blaTEM-1 (n=15) and blaOxA-1 (n=12). Plasmid mediated AmpC β-lactamases genes; blaACT-5 (n=1), blaDHA-1(n=2) and blaCMY-2 (n=4) were detected in seven isolates (14.2%). The blaOxA-48 (n=1) and blaIMP-1 (n=1) carbapenemases genes were detected among five carbapenem-resistant E. coli. Five isolates (10.2%) harboured qnr genes, qnrB1 (n=3), qnrB2 (n=1) and qnrS1 (n=1) type were detected. Thirty isolates (61.2%) were positive for aac(6')-Ib-cr gene. The class 1 integron was detected in twenty two (44.8%) isolates. Phylogenetic grouping revealed that 22 (44.8%) isolates belonged to group A, while 15 (30.6%), 11 (22.4%) and 1 (2%) belonged to B2, D and B1. Results of conjugation experiments indicated that blaCTx-M-15, blaTEM-1, blaOxA-1, aac(6')-Ib-cr and qnrB1 genes were co-ransferred and that these genes were carried by a conjugative plasmid of high molecular weight. The results of this work reports the genetic diversity of ESBL genes, with the CTX-M-15 enzyme being the most common among ESBL-producing E. coli in Moroccan community. © 2013 Elsevier Ltd.


Khyatti M.,Pasteur Institute of Morocco | Trimbitas R.-D.,Pasteur Institute of Morocco | Zouheir Y.,Pasteur Institute of Morocco | Benani A.,Pasteur Institute of Morocco | And 2 more authors.
European Journal of Public Health | Year: 2014

The epidemiological transition has reduced infectious diseases mortality in most European countries, yet increased migrant influx risks importing diseases. All reported prevalence rates must be considered on a case-by-case basis depending on the disease in question, respective European Union (EU) country and migratory patterns at work. Tuberculosis has seen a re-emergence in Europe and is concentrated among migrants. Migrants arriving from North Africa (NA) and sub-Saharan Africa (SSA) carry higher rates of hepatitis C and B than the local EU population. The human immunodeficiency virus (HIV) impact of NA migrants to Europe is very low but a hallmark of the HIV epidemic is the penetration and circulation of non-B strains, recombinant forms and HIV-drug-resistant profiles through SSA migrants using NA as a transit point into Europe. Leishmaniasis is a re-emerging zoonotic disease prevalent to Southern Europe although not specifically isolated in migrant groups. Although not endemic in NA countries, malaria represents a risk in terms of re-emergence in Europe through transitory migrants arriving from SSA with the destination to Europe. Schistosomiasis has been largely eliminated from NA. High migrant flux into European countries has resulted in changing patterns of communicable disease and collectively requires a continuous surveillance. World Health Organization guidelines recommend targeted screening and preventative vaccination, followed by integration of migrants into the local health-care systems allowing for long-term treatment and follow-up. Finally, effective public health campaigns as a form of prevention are essential for the mitigation of disease dissemination in the migrant pool and for second-generation children of migrants. © 2014 The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.


Ezzikouri S.,Pasteur Institute of Morocco | Pineau P.,Institute Pasteur Paris | Benjelloun S.,Pasteur Institute of Morocco
Journal of Medical Virology | Year: 2013

Hepatitis C is a global health problem with a worldwide prevalence of about 3% (around 170 million people). Hepatitis C virus (HCV) is major concern in the Maghreb countries, Algeria, Libya, Mauritania, Morocco, and Tunisia, but no detailed description of its epidemiology in the region is available. In the present review, a systematic search was undertaken covering HCV data available in peer-reviewed databases as well as institutional reports and regional conference meeting abstracts from the Maghreb countries. Reports written in English and French were included in this analysis. Estimates of national and regional prevalence of HCV infection (based on anti-HCV antibody) and of the size of patient populations were performed. In addition, the molecular features of the circulating viral strains in the region are discussed. A substantial proportion, 1.2-1.9% of the Maghreb inhabitants, have anti-HCV antibodies. Genotype 1b predominates among viral strains in all countries except in Libya, where genotype 4 is dominant as in neighboring Egypt. This epidemiological situation is of significant concern, and requires urgent, broad, and active intervention for the prevention and control of HCV. More specifically, the application of state-of-the-art hygiene procedures and rigorous controls in medical disciplines such as hemodialysis, transfusion, endoscopic procedures, and dentistry is necessary to reduce significantly the number of new infections in the region. © 2013 Wiley Periodicals, Inc.


Ezzikouri S.,Pasteur Institute of Morocco | Pineau P.,Institute Pasteur Paris | Benjelloun S.,Pasteur Institute of Morocco
Liver International | Year: 2013

Hepatitis B virus (HBV) represents an important health problem in the Maghreb countries, Algeria, Libya, Mauritania, Morocco and Tunisia, but no detailed synthesis of its epidemiology is available. In this review, we systematically searched for data about HBV in the Maghreb in peer-reviewed databases and included in our analysis works written in English and French, as well as institutional reports and regional conference meeting abstracts. We estimated national and regional prevalence of chronic HBV infection. In addition, we discuss molecular features of the viral strains circulating in the region. Data analysis suggests that in the Maghreb region HBs antigen carriage concerns 1.8-4.9% of the population for an estimated number of 2.7 million persons. Genotype D, subtype D7, is predominant and mutations in the precore region of HBV genome are highly prevalent. This epidemiological situation requires obviously widespread active interventions for prevention and control. In addition, anti-hepatitis B vaccination programme should be applied with the utmost discipline in the five countries considered in this present review. This systematic review will, hopefully, increase knowledge at disposal of Public Health authorities, enabling better resource allocation and healthcare delivery. The present synthesis intends to stimulate policies aiming at preventing the spread of HBV, keeping in mind that eradication of the virus from Maghrebi populations should be the ultimate objective of Public Health authorities. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Ezzikouri S.,Pasteur Institute of Morocco | Alaoui R.,Service de Medecine B | Tazi S.,Pasteur Institute of Morocco | Nadir S.,Service de Medecine B | And 3 more authors.
Infection, Genetics and Evolution | Year: 2014

Recent reports revealed an association between variation in the PNPLA3 gene and alcohol-induced hepatocellular carcinoma among Europeans. We have assessed whether the PNPLA3 rs738409 (I148M) polymorphism may also affect the resolution and/or the progression of hepatitis C in a Moroccan cohort.Genotype and allele frequencies at rs738409 were determined using a TaqMan 5' allelic discrimination assay in 437 individuals. Among them, 230 patients had a persistent infection with hepatitis C virus (HCV) with 129 patients affected by a chronic hepatitis and 101 patients by a hepatocellular carcinoma (HCC). In addition, we analyzed 75 individuals who naturally cleared HCV and 132 healthy subjects.Variation at rs738409 was not associated with significant changes in resolution rate of hepatitis C. By contrast, M/M genotype, present at higher frequencies (22.8%) in HCC patients than in patients with chronic hepatitis C (8.5%, P= 0.004) or control individuals (9.1%, P= 0.005) was associated with a 3-fold increase of liver cancer risk.In North African subjects, the PNPLA3 I148M variant apparently stimulates liver cancer development without interfering on the HCV clearance process. This polymorphism may, therefore, represent a valuable genetic marker to monitor liver cancer risk in populations from the Southern bank of the Mediterranean. © 2013 Elsevier B.V.


Ezzikouri S.,Pasteur Institute of Morocco | Alaoui R.,Service de Medecine B | Rebbani K.,Pasteur Institute of Morocco | Brahim I.,Pasteur Institute of Morocco | And 6 more authors.
PLoS ONE | Year: 2013

Background: Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population. Methods: We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay. Results: The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99-11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19-66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99-3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08-8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40-3.93; p = 0.0100). Conclusions: In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection. © 2013 Ezzikouri et al.


Oukkache N.,Pasteur Institute of Morocco | Lalaoui M.,Pasteur Institute of Morocco | Ghalim N.,Pasteur Institute of Morocco
Journal of Venomous Animals and Toxins Including Tropical Diseases | Year: 2012

Ophidian envenomation accidents constitute a serious public health problem in many countries around the globe. Over 5 million such accident cases occur each year causing more than 100,000 deaths. In Africa, more than 20,000 deaths per year are registered while 400,000 envenomation victims retain severe and permanent functional sequelae. In Morocco, snakebites are frequent and of greater severity in children. They occur mostly in rural areas. The incidence of these bites remains poorly understood and vastly underestimated. The epidemiological data are not well known due to the absence of a national registry, whereas a significant proportion of envenomations receive only traditional treatment methods in non-medical intensive care. This prompted us to investigate the enzymatic and biological properties of venom biochemical constituents from two of the most dangerous snake venoms in Morocco: Cerastes cerastes (Cc) and Macrovipera mauritanica (Mm). Also, we studied the immune cross-reactivity of Cc and Mm venoms in comparison to that of another important dangerous Moroccan viper, Bitis arietans (Ba), to identify the best candidates (venom or a mixture of venoms) for producing the most efficient and protective antivenom. In the present study, we report a preliminary venom characterization of Cc and Mm and the cross-reactivity that may exist between their venoms and Ba. These venoms are known to be highly toxic and contain several proteins that differ by molecular weights. Interestingly, both Cc and Mm venoms are characterized by intense hemorrhagic and phospholipase A2 activities and their ability to degrade the α and γ chains of fibrinogen. They display very low proteolysis through the casein test. After injection into mice, Cc and Mm induce myonecrosis in skeletal muscles, which most likely reflects direct action of myotoxins and indirect action of hemorrhagic molecules present in these venoms. In mice, this myonecrosis diminishes serum creatine phosphokinase (CPK) levels. As expected, Cc venom is immunogenic and induces highly protective antivenom against Mm and Ba venom antigens. This protective capacity is similar to that of the antivenom produced against the Mm venom. © CEVAP 2012.

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