Background: Availability and access to the detection of resistance to anti-tuberculosis drug srem... more Background: Availability and access to the detection of resistance to anti-tuberculosis drug sremains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi.Objectives: We aimed to determine mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis strains which were defined as resistant to rifampicin by the Xpert MTB/RIF assay.Methods: Rifampicin-resistant isolates from 43 adult patients (≥ 18 years) from various districts of Malawi were characterised for mutations in the RRDR (codons 507–533) of the rpoB gene by DNA sequencing.Results: Mutations were found in 37/43 (86%) of the resistant isolates in codons 511, 512, 513,516, 522, 526 and 531. The most common mutations were in codons 526 (38%), 531 (29.7%) and 516 (16.2%). Mutations were not f...
The genus Mycobacterium represents more than 120 species including important pathogens of human a... more The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species.
Please help us populate SUNScholar with the post print version of this article. It can be e-maile... more Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]êre Biologie & Mensgenetik
We studied 422 patients with urethral discharge recruited from 4 sentinel sites in Morocco to det... more We studied 422 patients with urethral discharge recruited from 4 sentinel sites in Morocco to determine sociodemographic characteristics, history of STI infection, infecting organism and antibiotic susceptibility of Neisseria gonorrhoeae. The mean age of the sample was 28 years [range 16-67 years], and most were single, had multiple sex partners without taking protective measures and came from all social backgrounds; 59.9% had a history of a previous STI. The majority [87%] of the infections were the acute form. By polymerase chain reaction of urine samples of 399 patients, 41.6% had N. gonorrhoeae infection, 6.3% Chlamidia trachomatis and 10.8% both organisms; in 41.4% no organism was identified. N. gonorrhoeae was strongly susceptible to ciprofloxacin.
Nous avons conduit en 2012 une étude transversale dans une sélection de 12 provinces/préfectures ... more Nous avons conduit en 2012 une étude transversale dans une sélection de 12 provinces/préfectures au Maroc pour déterminer les délais de consultation (délai patient), de diagnostic et de mise sous traitement (délai système de santé) chez les nouveaux cas de tuberculose pulmonaire à microscopie positive et les facteurs en relation avec ces délais. L'échantillon comprenait 250 patients, éligibles et consentants, qui ont été interviewés lors de leur enregistrement aux Centres de Diagnostic de la Tuberculose et des Maladies Respiratoires (CDTMR) ou aux Centres de Santé Intégrés (CSI), en utilisant un questionnaire structuré et prétesté. Le délai total médian est de 46 jours (intervalle interquartile [IIQ] : 29-84 jours). Le délai patient (médiane : 20 jours ; IIQ : 8-47) est supérieur au délai système de santé (médiane : 15 jours ; IIQ : 7-35). Être analphabète, croire à la disparition spontanée des symptômes, avoir des contraintes économiques ou peur du diagnostic et de l'isolement social sont associés au délai patient. Consulter en premier dans le secteur privé ou faire trois consultations au moins avant le diagnostic sont associés au délai système de santé.
The objective of this study was to describe the risks and human health outcomes associated with a... more The objective of this study was to describe the risks and human health outcomes associated with attendance at the Moulay Abdellah Amghar moussem (a pre-planned mass gathering attracting more than 360 000 participants) for the purposes of public health prevention, planning, preparedness and response. We performed an environmental health risk assessment and retrospectively reviewed local health centre records before, during and after the event. In addition, standardized interviews with key stakeholders were performed to qualitatively evaluate local public health preparedness and response capacities. During the event, average daily health centre visits increased 5-fold. The sex ratio of health-care visits changed significantly from an average of 1.8:1 female:male visits per day to 1.2:1. The proportion of injuries varied from an average of 3.7% pre-and postevent to 14.8% (P < 0.01) during the event. A significant increase in digestive diseases was also observed during the event. Recommendations include increasing accessibility to free sanitation and hygiene facilities and improving health communications concerning hand washing and food and water safety.
Zaër region of Morocco in 2007 among 267 barbers and 529 clients, all men with no history of hepa... more Zaër region of Morocco in 2007 among 267 barbers and 529 clients, all men with no history of hepatitis B (HBV) vaccination. The overall prevalence of HBV seropositivity was 28.1% in barbers and 25.1% in clients; 1.9% and 1.7% respectively had active HBV (HBsAg positive). Risk factors for HBV included older age, low educational level, urban living, being married, history of transfusion, lack of current heterosexual relationship and liver-associated symptoms. Observations showed that HBV seropositivity was lower in clean barbershops and those using alum as an antispetic. The rate of PCR-confirmed hepatitis C virus (HCV) was only 1.1% and 1.3% in barbers and clients respectively, and was associated with increased age, drug use, history of surgery and symptoms of liver disease. Less than 1% of barbers were aware of HBV or HCV as causative agents of liver disease or jaundice.
The xcp genes are required for protein secretion by Pseudomonas aeruginosa. They are involved in ... more The xcp genes are required for protein secretion by Pseudomonas aeruginosa. They are involved in the second step of the process, i.e. the translocation across the outer membrane, after the exoproteins have reached the periplasm in a signal peptide dependent fashion. The nucleotide sequence of a 2.5 kb DNA fragment containing xcp genes showed at least two complete open reading frames, potentially encoding proteins with molecular weights of 41 and 19 kd. Products with these apparent molecular weights were identified after expression of the DNA fragment in vitro and in vivo. Subcloning and complementation experiments showed that both proteins are required for secretion. The two products are located in the inner membrane and share highly significant homologies with the PulL and PulM proteins which are required for the specific secretion of pullulanase in Kebsiella pneumoniae. These homologies reveal the existence of a common mechanism for protein secretion in Pseudomonas aeruginosa and KlebsieUla pneumoniae.
patients still get transient side-effects especially at the beginning of taking this regimen due ... more patients still get transient side-effects especially at the beginning of taking this regimen due to efavirenz as such, regular monitoring and thorough counselling of all patients on the side effects of tenofovir-based regimen and transient nature of side effects is needed. A large scale study to be done to obtain data on longterm side-effects of tenofovir-based regimen most possibly renal impairment due to tenofovir or efavirenz-induced gynecomastia.
Introduction Le diabete est associe avec un risque plus important de developper une maladie infec... more Introduction Le diabete est associe avec un risque plus important de developper une maladie infectieuse notamment en Afrique. Ainsi l’association du diabete a la tuberculose est bien etablie. Ces observations sont d’une grande importance dans les pays tel que le Maroc qui vit une transition epidemiologique dite de la double charge c’est-a-dire le groupe tout entier des maladies non transmissibles dont les facteurs de risques sont communs vient s’ajouter aux maladies transmissibles qui continuent de sevir. Methodes L’etude porte sur le premier semestre de l’annee 2013. Il s’agit d’une etude epidemiologique descriptive retrospective basee sur l’exploitation des dossiers de tuberculeux du centre de reference my lhassan province de Kenitra Maroc. Elle portait sur 253 patients tuberculeux referes durant la periode consideree. Les variables etudiees portaient sur l’âge, le sexe, la forme de la tuberculose (pulmonaire et extrapulmonaire), le type de diabete, la survenue ou non de complications et l’evolution. La saisie et l’analyse des donnees ont ete faites par le logiciel SPSS.13.0. Resultats Au total, 253 patients tuberculeux ont ete recus au cours de cette periode. L’âge moyen des patients etait de 38 ± 18,5 ans. La proportion de femmes etait de 42,3 % (107) et celle des hommes etait de 57,7 % (146). Parmi les 146 cas (57,7 %) de tuberculose pulmonaire, 4 % (10) etaient des cas TPM−, 7,1 % (18) etaient des cas TPM, 46,6 % (118) etaient des cas TPM+. Par ailleurs, nous avons eu 107 cas (42,3 %) de tuberculose extrapulmonaire repartis en ganglionnaire 12,6 % (32), mal de Pott 3,6 % (9), miliaire tuberculose 2 % (5), peritoneale 9,1 % (23), et pleurales 15,4 %(39). Parmi l’ensemble des malades 20,6 % (52) avaient une association diabete–tuberculose dont 51,9 % (27) diabetiques insulino-dependants et 48,1 % (25) diabetiques non insulino-dependants et 6 % (15) ont fait une decompensation de leur diabete. Les patients tuberculeux diabetiques etaient plus âges (53,3 ± 14,7 ans versus 34,1 ± 17,2 ans) ( p p p p Conclusion La forme et l’evolution de la tuberculose sont differentes entre les patients diabetiques et non diabetiques. Il est donc tres interessent de prendre en consideration la presence de cette comorbidite lors du diagnostic, du traitement et de la surveillance de la tuberculose, mais egalement le depistage systematique du diabete chez les tuberculeux.
Cellular and molecular biology (Noisy-le-Grand, France), 2012
Tuberculosis (TB) is an infectious, devastating and contagious disease, which infects third of th... more Tuberculosis (TB) is an infectious, devastating and contagious disease, which infects third of the global population worldwide with high rates of incidence in the developing countries, where the health care providers face a serious problem and a real challenge during their clinical practice for controlling and preventing the transmission of this illness. Indeed the first step of control is the correct diagnosis and the initiation of the drug treatment regimen at the early stage of infection, which mandate the rapidity of screening and the accuracy of laboratory testing. In this paper we aim to highlight the different actual techniques, regarding the rapid screening and diagnosis of tuberculosis.
Background: Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circ... more Background: Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings: Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004-2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1-ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2-modern/TbD12/PGG1 group (Beijing, CAS), group 3-evolutionary recent/TbD12/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion: The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the ''evolutionary recent'' TbD12/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco.
In Pseudomonas aeruginosa, several exoproteins synthesized with a signal sequence (elastase, lipa... more In Pseudomonas aeruginosa, several exoproteins synthesized with a signal sequence (elastase, lipase, phospholipases, alkaline phosphatase and exotoxin A) are secreted by a two-step mechanism. They first cross the inner membrane in a signal sequence-dependent way, and are further translocated across the outer membrane in a second step requiring secretion functions encoded by several xcp genes. Ten xcp genes have already been characterized (Bally et al., 1992a). In this study, two additional xcp genes, xcpP and xcpQ, are described. They are located in the 40 min region of the chromosome where they probably define an operon, divergent from the xcpR-Z operon previously characterized in this region. These two genes encode two proteins, XcpP and XcpQ, similar to PulC and PulD of the pul system of Klebsiella oxytoca. Moreover, the two divergent operons share a common regulation which is growth-phase dependent.
The xcp genes are required for the secretion of most extracellular proteins by Pseudomonas aerugi... more The xcp genes are required for the secretion of most extracellular proteins by Pseudomonas aeruginosa. The products of these genes are essential for the transport of exoproteins across the outer membrane after they have reached the periptasm via a signal sequence-dependent pathway. To date, analysis of three xcp genes has suggested the conservation of this secretion pathway in many Gram-negative bacteria. Furthermore, the xcpA gene was shown to be identical to pilD, which encodes a peptidase involved in the processing of f imbrial (pili) subunits, suggesting a connection between pili biogenesis and protein secretion. Here the nucleotide sequences of seven other xcp genes, designated xcpR to-X, are presented. The W-termini of four of the encoded Xcp proteins display similarity to the N-termini of type IV pili, suggesting that XcpA is involved in the processing of these Xcp proteins. This could indeed be demonstrated in vivo. Furthermore, two other proteins, XcpR and XcpS, show similarity to the PilB and PilC proteins required for fimbriae assembly. Since XcpR and PilB display a canonical nucleotide-binding site, ATP hydrolysis may provide energy for both systems.
The virulence of the opportunistic pathogen Pseudomonas aeruginosa is largely dependent upon the ... more The virulence of the opportunistic pathogen Pseudomonas aeruginosa is largely dependent upon the extracellular production of a number of secreted proteins with toxic or degradative activities. The synthesis of several exoenzymes is controlled in a cell-densitydependent manner by two interlinked quorum-sensing systems. Their secretion across the outer membrane occurs through the Xcp translocation machinery. The xcp locus located at 40 min on the chromosome consists of two divergently transcribed operons, namely xcpPQ and xcpR to xcpZ. In this study, transcriptional fusions were constructed between the xcpP and xcpR genes and the lacZ reporter. Transcriptional activation of the xcpP and xcpR genes in P. aeruginosa is growth-phase dependent and the lasR-lasI autoinduction system is required for this control. In the heterologous host Escherichia coli, the lasR gene product, together with its cognate autoinducer N-(3oxododecanoyl)-L-homoserine lactone (OdDHL), activates both the xcpP-lacZ and the xcpR-lacZ gene fusion. The second P. aeruginosa quorum-sensing modulon rhlR-rhlI (vsmR-vsmI) is also involved in the control of the xcp genes. Expression of the lacZ fusions is strongly reduced in PANO67, a pleiotropic mutant defective in the production of N-acyl-homoserine lactones responsible for the activation of RhlR. Furthermore, introduction of the lasR mutation in PANO67 results in additional diminution of xcpR transcription, indicating that the two systems can regulate their target genes independently. These data demonstrate that expression of the xcp secretion system depends on a complex regulatory network involving cell-cell signalling which controls production and secretion of virulence-associated factors.
In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-po... more In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-positive TB patients in Morocco were studied by spoligotyping and 12-loci MIRU-VNTR typing methods to characterize prevalent genotypes (n = 219 isolates from 208 patients). Spoligotyping resulted in 39 unique patterns and 167 strains in 30 clusters (2-50 strains per cluster). Comparison with international database showed that 29 of 39 unique patterns matched existing shared spoligotype international types (SITs). Nine shared types containing 10 strains were newly created (SIT 2891 to SIT 2899); this led to the description of 69 SITs with 206 strains and two orphan patterns. The most prevalent spoligotype was SIT42 (LAM; n = 50 or 24% of isolates). The repartition of strains according to major MTBC clades was as follows LAM (46.1%)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Haarlem (26%) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;ill-defined T superfamily (22.6%) and S clade (0.96%). On the other hand, Beijing, CAS (Central Asian) and EAI (East-African Indian) strains were absent in this setting. Subsequent 12-Loci MIRU typing resulted in a total of 25 SIT/MIT clusters (n = 66 isolates, 2-6 isolates per cluster), with a resulting recent transmission rate of 22.3%. The MIRU-VNTR patterns corresponded to 69 MITs for 138 strains and 46 orphan patterns. The most frequent patterns were MIT43 (n = 8), MIT9 (n = 7) and MIT42 (n = 7). HGDI analysis of the 12 MIRU loci showed that loci 10, 23 and 40 were highly discriminative in our setting. The results also underlined the usefulness of spoligotyping and MIRU-VNTR to detect mixed infections among certain of our TB patients. Globally, the results obtained showed that TB is almost exclusively transmitted in Morocco through evolutionary-modern MTBC lineages belonging to principal genetic groups 2/3 strains (Haarlem, LAM, T), with a high level of biodiversity seen by MIRU typing. This study provides with a 1st global snapshot of MTBC population structure in Morocco, and validates the potential use of spoligotyping in conjunction with minisatellites for future investigations in Morocco that should in future ideally include optimized 15- or 24-loci MIRU-VNTRs.
BackgroundLittle is known about HIV-1 subtype distribution in Morocco. Some data suggest an emerg... more BackgroundLittle is known about HIV-1 subtype distribution in Morocco. Some data suggest an emergence of new HIV subtypes. We conducted phylogenetic analysis on a nationally representative sample of 60 HIV-1 viral specimens collected during 2004-2005 through the Morocco national HIV sentinel surveillance survey.ResultsWhile subtype B is still the most prevalent, 23.3% of samples represented non-B subtypes, the majority of which were classified as CRF02_AG (15%). Molecular clock analysis confirmed that the initial introduction of HIV-1B in Morocco probably came from Europe in the early 1980s. In contrast, the CRF02_AG strain appeared to be introduced from sub-Saharan Africa in two separate events in the 1990s.ConclusionsSubtype CRF02_AG has been emerging in Morocco since the 1990s. More information about the factors introducing HIV subtype-specific transmission will inform the prevention strategy in the region.
Background: Availability and access to the detection of resistance to anti-tuberculosis drug srem... more Background: Availability and access to the detection of resistance to anti-tuberculosis drug sremains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi.Objectives: We aimed to determine mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis strains which were defined as resistant to rifampicin by the Xpert MTB/RIF assay.Methods: Rifampicin-resistant isolates from 43 adult patients (≥ 18 years) from various districts of Malawi were characterised for mutations in the RRDR (codons 507–533) of the rpoB gene by DNA sequencing.Results: Mutations were found in 37/43 (86%) of the resistant isolates in codons 511, 512, 513,516, 522, 526 and 531. The most common mutations were in codons 526 (38%), 531 (29.7%) and 516 (16.2%). Mutations were not f...
The genus Mycobacterium represents more than 120 species including important pathogens of human a... more The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species.
Please help us populate SUNScholar with the post print version of this article. It can be e-maile... more Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]êre Biologie & Mensgenetik
We studied 422 patients with urethral discharge recruited from 4 sentinel sites in Morocco to det... more We studied 422 patients with urethral discharge recruited from 4 sentinel sites in Morocco to determine sociodemographic characteristics, history of STI infection, infecting organism and antibiotic susceptibility of Neisseria gonorrhoeae. The mean age of the sample was 28 years [range 16-67 years], and most were single, had multiple sex partners without taking protective measures and came from all social backgrounds; 59.9% had a history of a previous STI. The majority [87%] of the infections were the acute form. By polymerase chain reaction of urine samples of 399 patients, 41.6% had N. gonorrhoeae infection, 6.3% Chlamidia trachomatis and 10.8% both organisms; in 41.4% no organism was identified. N. gonorrhoeae was strongly susceptible to ciprofloxacin.
Nous avons conduit en 2012 une étude transversale dans une sélection de 12 provinces/préfectures ... more Nous avons conduit en 2012 une étude transversale dans une sélection de 12 provinces/préfectures au Maroc pour déterminer les délais de consultation (délai patient), de diagnostic et de mise sous traitement (délai système de santé) chez les nouveaux cas de tuberculose pulmonaire à microscopie positive et les facteurs en relation avec ces délais. L'échantillon comprenait 250 patients, éligibles et consentants, qui ont été interviewés lors de leur enregistrement aux Centres de Diagnostic de la Tuberculose et des Maladies Respiratoires (CDTMR) ou aux Centres de Santé Intégrés (CSI), en utilisant un questionnaire structuré et prétesté. Le délai total médian est de 46 jours (intervalle interquartile [IIQ] : 29-84 jours). Le délai patient (médiane : 20 jours ; IIQ : 8-47) est supérieur au délai système de santé (médiane : 15 jours ; IIQ : 7-35). Être analphabète, croire à la disparition spontanée des symptômes, avoir des contraintes économiques ou peur du diagnostic et de l'isolement social sont associés au délai patient. Consulter en premier dans le secteur privé ou faire trois consultations au moins avant le diagnostic sont associés au délai système de santé.
The objective of this study was to describe the risks and human health outcomes associated with a... more The objective of this study was to describe the risks and human health outcomes associated with attendance at the Moulay Abdellah Amghar moussem (a pre-planned mass gathering attracting more than 360 000 participants) for the purposes of public health prevention, planning, preparedness and response. We performed an environmental health risk assessment and retrospectively reviewed local health centre records before, during and after the event. In addition, standardized interviews with key stakeholders were performed to qualitatively evaluate local public health preparedness and response capacities. During the event, average daily health centre visits increased 5-fold. The sex ratio of health-care visits changed significantly from an average of 1.8:1 female:male visits per day to 1.2:1. The proportion of injuries varied from an average of 3.7% pre-and postevent to 14.8% (P < 0.01) during the event. A significant increase in digestive diseases was also observed during the event. Recommendations include increasing accessibility to free sanitation and hygiene facilities and improving health communications concerning hand washing and food and water safety.
Zaër region of Morocco in 2007 among 267 barbers and 529 clients, all men with no history of hepa... more Zaër region of Morocco in 2007 among 267 barbers and 529 clients, all men with no history of hepatitis B (HBV) vaccination. The overall prevalence of HBV seropositivity was 28.1% in barbers and 25.1% in clients; 1.9% and 1.7% respectively had active HBV (HBsAg positive). Risk factors for HBV included older age, low educational level, urban living, being married, history of transfusion, lack of current heterosexual relationship and liver-associated symptoms. Observations showed that HBV seropositivity was lower in clean barbershops and those using alum as an antispetic. The rate of PCR-confirmed hepatitis C virus (HCV) was only 1.1% and 1.3% in barbers and clients respectively, and was associated with increased age, drug use, history of surgery and symptoms of liver disease. Less than 1% of barbers were aware of HBV or HCV as causative agents of liver disease or jaundice.
The xcp genes are required for protein secretion by Pseudomonas aeruginosa. They are involved in ... more The xcp genes are required for protein secretion by Pseudomonas aeruginosa. They are involved in the second step of the process, i.e. the translocation across the outer membrane, after the exoproteins have reached the periplasm in a signal peptide dependent fashion. The nucleotide sequence of a 2.5 kb DNA fragment containing xcp genes showed at least two complete open reading frames, potentially encoding proteins with molecular weights of 41 and 19 kd. Products with these apparent molecular weights were identified after expression of the DNA fragment in vitro and in vivo. Subcloning and complementation experiments showed that both proteins are required for secretion. The two products are located in the inner membrane and share highly significant homologies with the PulL and PulM proteins which are required for the specific secretion of pullulanase in Kebsiella pneumoniae. These homologies reveal the existence of a common mechanism for protein secretion in Pseudomonas aeruginosa and KlebsieUla pneumoniae.
patients still get transient side-effects especially at the beginning of taking this regimen due ... more patients still get transient side-effects especially at the beginning of taking this regimen due to efavirenz as such, regular monitoring and thorough counselling of all patients on the side effects of tenofovir-based regimen and transient nature of side effects is needed. A large scale study to be done to obtain data on longterm side-effects of tenofovir-based regimen most possibly renal impairment due to tenofovir or efavirenz-induced gynecomastia.
Introduction Le diabete est associe avec un risque plus important de developper une maladie infec... more Introduction Le diabete est associe avec un risque plus important de developper une maladie infectieuse notamment en Afrique. Ainsi l’association du diabete a la tuberculose est bien etablie. Ces observations sont d’une grande importance dans les pays tel que le Maroc qui vit une transition epidemiologique dite de la double charge c’est-a-dire le groupe tout entier des maladies non transmissibles dont les facteurs de risques sont communs vient s’ajouter aux maladies transmissibles qui continuent de sevir. Methodes L’etude porte sur le premier semestre de l’annee 2013. Il s’agit d’une etude epidemiologique descriptive retrospective basee sur l’exploitation des dossiers de tuberculeux du centre de reference my lhassan province de Kenitra Maroc. Elle portait sur 253 patients tuberculeux referes durant la periode consideree. Les variables etudiees portaient sur l’âge, le sexe, la forme de la tuberculose (pulmonaire et extrapulmonaire), le type de diabete, la survenue ou non de complications et l’evolution. La saisie et l’analyse des donnees ont ete faites par le logiciel SPSS.13.0. Resultats Au total, 253 patients tuberculeux ont ete recus au cours de cette periode. L’âge moyen des patients etait de 38 ± 18,5 ans. La proportion de femmes etait de 42,3 % (107) et celle des hommes etait de 57,7 % (146). Parmi les 146 cas (57,7 %) de tuberculose pulmonaire, 4 % (10) etaient des cas TPM−, 7,1 % (18) etaient des cas TPM, 46,6 % (118) etaient des cas TPM+. Par ailleurs, nous avons eu 107 cas (42,3 %) de tuberculose extrapulmonaire repartis en ganglionnaire 12,6 % (32), mal de Pott 3,6 % (9), miliaire tuberculose 2 % (5), peritoneale 9,1 % (23), et pleurales 15,4 %(39). Parmi l’ensemble des malades 20,6 % (52) avaient une association diabete–tuberculose dont 51,9 % (27) diabetiques insulino-dependants et 48,1 % (25) diabetiques non insulino-dependants et 6 % (15) ont fait une decompensation de leur diabete. Les patients tuberculeux diabetiques etaient plus âges (53,3 ± 14,7 ans versus 34,1 ± 17,2 ans) ( p p p p Conclusion La forme et l’evolution de la tuberculose sont differentes entre les patients diabetiques et non diabetiques. Il est donc tres interessent de prendre en consideration la presence de cette comorbidite lors du diagnostic, du traitement et de la surveillance de la tuberculose, mais egalement le depistage systematique du diabete chez les tuberculeux.
Cellular and molecular biology (Noisy-le-Grand, France), 2012
Tuberculosis (TB) is an infectious, devastating and contagious disease, which infects third of th... more Tuberculosis (TB) is an infectious, devastating and contagious disease, which infects third of the global population worldwide with high rates of incidence in the developing countries, where the health care providers face a serious problem and a real challenge during their clinical practice for controlling and preventing the transmission of this illness. Indeed the first step of control is the correct diagnosis and the initiation of the drug treatment regimen at the early stage of infection, which mandate the rapidity of screening and the accuracy of laboratory testing. In this paper we aim to highlight the different actual techniques, regarding the rapid screening and diagnosis of tuberculosis.
Background: Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circ... more Background: Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings: Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004-2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1-ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2-modern/TbD12/PGG1 group (Beijing, CAS), group 3-evolutionary recent/TbD12/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion: The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the ''evolutionary recent'' TbD12/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco.
In Pseudomonas aeruginosa, several exoproteins synthesized with a signal sequence (elastase, lipa... more In Pseudomonas aeruginosa, several exoproteins synthesized with a signal sequence (elastase, lipase, phospholipases, alkaline phosphatase and exotoxin A) are secreted by a two-step mechanism. They first cross the inner membrane in a signal sequence-dependent way, and are further translocated across the outer membrane in a second step requiring secretion functions encoded by several xcp genes. Ten xcp genes have already been characterized (Bally et al., 1992a). In this study, two additional xcp genes, xcpP and xcpQ, are described. They are located in the 40 min region of the chromosome where they probably define an operon, divergent from the xcpR-Z operon previously characterized in this region. These two genes encode two proteins, XcpP and XcpQ, similar to PulC and PulD of the pul system of Klebsiella oxytoca. Moreover, the two divergent operons share a common regulation which is growth-phase dependent.
The xcp genes are required for the secretion of most extracellular proteins by Pseudomonas aerugi... more The xcp genes are required for the secretion of most extracellular proteins by Pseudomonas aeruginosa. The products of these genes are essential for the transport of exoproteins across the outer membrane after they have reached the periptasm via a signal sequence-dependent pathway. To date, analysis of three xcp genes has suggested the conservation of this secretion pathway in many Gram-negative bacteria. Furthermore, the xcpA gene was shown to be identical to pilD, which encodes a peptidase involved in the processing of f imbrial (pili) subunits, suggesting a connection between pili biogenesis and protein secretion. Here the nucleotide sequences of seven other xcp genes, designated xcpR to-X, are presented. The W-termini of four of the encoded Xcp proteins display similarity to the N-termini of type IV pili, suggesting that XcpA is involved in the processing of these Xcp proteins. This could indeed be demonstrated in vivo. Furthermore, two other proteins, XcpR and XcpS, show similarity to the PilB and PilC proteins required for fimbriae assembly. Since XcpR and PilB display a canonical nucleotide-binding site, ATP hydrolysis may provide energy for both systems.
The virulence of the opportunistic pathogen Pseudomonas aeruginosa is largely dependent upon the ... more The virulence of the opportunistic pathogen Pseudomonas aeruginosa is largely dependent upon the extracellular production of a number of secreted proteins with toxic or degradative activities. The synthesis of several exoenzymes is controlled in a cell-densitydependent manner by two interlinked quorum-sensing systems. Their secretion across the outer membrane occurs through the Xcp translocation machinery. The xcp locus located at 40 min on the chromosome consists of two divergently transcribed operons, namely xcpPQ and xcpR to xcpZ. In this study, transcriptional fusions were constructed between the xcpP and xcpR genes and the lacZ reporter. Transcriptional activation of the xcpP and xcpR genes in P. aeruginosa is growth-phase dependent and the lasR-lasI autoinduction system is required for this control. In the heterologous host Escherichia coli, the lasR gene product, together with its cognate autoinducer N-(3oxododecanoyl)-L-homoserine lactone (OdDHL), activates both the xcpP-lacZ and the xcpR-lacZ gene fusion. The second P. aeruginosa quorum-sensing modulon rhlR-rhlI (vsmR-vsmI) is also involved in the control of the xcp genes. Expression of the lacZ fusions is strongly reduced in PANO67, a pleiotropic mutant defective in the production of N-acyl-homoserine lactones responsible for the activation of RhlR. Furthermore, introduction of the lasR mutation in PANO67 results in additional diminution of xcpR transcription, indicating that the two systems can regulate their target genes independently. These data demonstrate that expression of the xcp secretion system depends on a complex regulatory network involving cell-cell signalling which controls production and secretion of virulence-associated factors.
In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-po... more In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-positive TB patients in Morocco were studied by spoligotyping and 12-loci MIRU-VNTR typing methods to characterize prevalent genotypes (n = 219 isolates from 208 patients). Spoligotyping resulted in 39 unique patterns and 167 strains in 30 clusters (2-50 strains per cluster). Comparison with international database showed that 29 of 39 unique patterns matched existing shared spoligotype international types (SITs). Nine shared types containing 10 strains were newly created (SIT 2891 to SIT 2899); this led to the description of 69 SITs with 206 strains and two orphan patterns. The most prevalent spoligotype was SIT42 (LAM; n = 50 or 24% of isolates). The repartition of strains according to major MTBC clades was as follows LAM (46.1%)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; Haarlem (26%) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;ill-defined T superfamily (22.6%) and S clade (0.96%). On the other hand, Beijing, CAS (Central Asian) and EAI (East-African Indian) strains were absent in this setting. Subsequent 12-Loci MIRU typing resulted in a total of 25 SIT/MIT clusters (n = 66 isolates, 2-6 isolates per cluster), with a resulting recent transmission rate of 22.3%. The MIRU-VNTR patterns corresponded to 69 MITs for 138 strains and 46 orphan patterns. The most frequent patterns were MIT43 (n = 8), MIT9 (n = 7) and MIT42 (n = 7). HGDI analysis of the 12 MIRU loci showed that loci 10, 23 and 40 were highly discriminative in our setting. The results also underlined the usefulness of spoligotyping and MIRU-VNTR to detect mixed infections among certain of our TB patients. Globally, the results obtained showed that TB is almost exclusively transmitted in Morocco through evolutionary-modern MTBC lineages belonging to principal genetic groups 2/3 strains (Haarlem, LAM, T), with a high level of biodiversity seen by MIRU typing. This study provides with a 1st global snapshot of MTBC population structure in Morocco, and validates the potential use of spoligotyping in conjunction with minisatellites for future investigations in Morocco that should in future ideally include optimized 15- or 24-loci MIRU-VNTRs.
BackgroundLittle is known about HIV-1 subtype distribution in Morocco. Some data suggest an emerg... more BackgroundLittle is known about HIV-1 subtype distribution in Morocco. Some data suggest an emergence of new HIV subtypes. We conducted phylogenetic analysis on a nationally representative sample of 60 HIV-1 viral specimens collected during 2004-2005 through the Morocco national HIV sentinel surveillance survey.ResultsWhile subtype B is still the most prevalent, 23.3% of samples represented non-B subtypes, the majority of which were classified as CRF02_AG (15%). Molecular clock analysis confirmed that the initial introduction of HIV-1B in Morocco probably came from Europe in the early 1980s. In contrast, the CRF02_AG strain appeared to be introduced from sub-Saharan Africa in two separate events in the 1990s.ConclusionsSubtype CRF02_AG has been emerging in Morocco since the 1990s. More information about the factors introducing HIV subtype-specific transmission will inform the prevention strategy in the region.
Uploads
Papers by M. Akrim