Incidence of adverse reactions caused by first-line anti-tuberculosis drugs and treatment outcome of pulmonary tuberculosis patients in Morocco.

PURPOSE: The treatment of tuberculosis is associated with a high incidence of adverse reactions with different degrees of severity. The aim of this study was to determine the incidence of adverse reactions caused by first-line anti-tuberculosis drugs and to evaluate the treatment outcome of TB patients in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established for data collection from clinical charts of TB patients. The study was carried out in all the 18 centers located in the Rabat-Salé-Kénitra region of Morocco where tuberculosis is treated. Adverse reactions are evaluated from the start of TB treatment until its end by a specialist clinician. The treatment outcomes are evaluated, and the definitions and classifications of these outcomes are defined according to World Health Organization guidelines. RESULTS: Among a total number of 2532 patients treated for TB, the average age is 37.3 ± 16.4 years, 10.0% of patients produced adverse reactions. 7.4% of adverse reactions are gastrointestinal, 3.7% are cutaneous, 2.0% are hepatic, 1.14% are articular, 1.07% are immunoallergic, 0.7% are neuropsychiatric, and 0.1% are ocular. The treatment outcome of TB patients is 79.1% rate for successful treatment and 15.6% for unsuccessful treatment. CONCLUSION: Adverse reactions caused by anti-TB drugs are frequent among patients with TB. These ADRs must be followed up by a closer monitoring during anti-TB treatment period. Treatment success outcome in our study is slightly lower than the success rate target of WHO of at least 85%.

Treatment outcomes of drug resistant tuberculosis patients in Morocco: multi-centric prospective study.

BACKGROUND: Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco. RESULTS: In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients' age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327-14.292]). CONCLUSION: Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a prospective randomized study.

PURPOSE: Eradication rates following standard triple therapy for Helicobacter pylori infection are declining. Recent studies, conducted in a number of countries, have shown that sequential therapy for H. pylori infection yields high cure rates. AIM: To compare the efficacy and tolerability of a sequential regimen as a first-line treatment of H. pylori infection with a standard triple treatment regime in Morocco. METHODS: A total of 281 naive H. pylori-infected patients, confirmed by histological examination, were assigned randomly to one of two treatment groups: standard triple therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) + clarithromycin (500 mg bid) for 7 days] or sequential therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) for 5 days, followed by omeprazole (20 mg bid) + tinidazole (500 mg bid) + clarithromycin (500 mg bid) for an additional 5 days]. H. pylori eradication was checked 4-6 weeks after treatment initiation by using a ¹³C-urea breath test. Compliance and adverse events were assessed. RESULTS: The two groups did not differ significantly in gender, age, previous disease history, endoscopic and histological features and smoking. The intention-to-treat and per-protocol eradication rates were 65.9 and 71 % in the standard triple therapy group, and 82.8 and 89.9 % in the sequential therapy group, respectively. The eradication rate was significantly higher in the sequential therapy group than in the standard triple therapy group (p < 0.001), There was no statistically significant difference in compliance (97.5 vs. 96.3 %) and incidence of side-effects (27.5 vs. 27.9 %) between the two groups. CONCLUSIONS: Based on our results, we conclude that for eradication of H. pylori infection, the 10-day sequential therapy is more effective than the standard triple therapy and is equally tolerated. These results confirm those of other studies in other countries.

[Not Available]. / Les médicaments génériques et l'évolution de la consommation des antihypertenseurs au Maroc.

BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population.

[Generic drugs and the consumption trends of antihypertensives in Morocco]. / Les médicaments génériques et l'évolution de la consommation des antihypertenseurs au Maroc.

BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population.

The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population.

Major histocompatibility complex class II plays a key role in the immune response, by presenting processed antigens to CD4+ lymphocytes. Major histocompatibility complex class II expression is controlled at the transcriptional level by at least four trans-acting genes: CIITA, RFXANK, RFX5 and RFXAP. Defects in these regulatory genes cause MHC class II immunodeficiency, which is frequent in North Africa. The aim of this study was to describe the immunological and molecular characteristics of ten unrelated Moroccan patients with MHC class II deficiency. Immunological examinations revealed a lack of expression of MHC class II molecules at the surface of peripheral blood mononuclear cells, low CD4+ T lymphocyte counts and variable serum immunoglobulin (IgG, IgM and IgA) levels. In addition, no MHC class II (HLA DR) expression was observed on lymphoblasts. The molecular analysis identified the same homozygous 752delG26 mutation in the RFXANK genes of all patients. This finding confirms the association between the high frequency of the combined immunodeficiency and the defect in MHC class II expression and provides strong evidence for a founder effect of the 752delG26 mutation in the North African population. These findings should facilitate the establishment of molecular diagnosis and improve genetic counselling for affected Moroccan families.

Borrelia hispanica relapsing fever, Morocco.

We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species.

Spotted fever group rickettsiae in ticks, Morocco.

A total of 370 ticks, encompassing 7 species from 4 genera, were collected during 2002-2006 from domestic animals and vegetation in the Taza region of northeastern Morocco. Rickettsial DNA was identified in 101 ticks (27%) by sequencing PCR products of fragments of the citrate synthase and outer membrane protein genes of Rickettsia spp. Seven rickettsiae of the spotted fever group were identified, including 4 pathogens: R. aeschlimannii in Hyalomma marginatum marginatum, R. massiliae in Rhipicephalus sanguineus, R. slovaca in Dermacentor marginatus, and R. monacensis in Ixodes ricinus. Two suspected pathogens were also detected (R. raoultii in D. marginatus and R. helvetica in I. ricinus). An incompletely described Rickettsia sp. was detected in Haemaphysalis spp. ticks.

Genotype determination in Moroccan hepatitis B chronic carriers.

BACKGROUND: In Morocco, chronic liver disease related to hepatitis B virus (HBV) is a public health burden. Treatment of chronic hepatitis B is often complicated by the appearance of escape mutants after treatment with nucleoside analogs, especially with genotypes responsible for the more severe form of the disease. OBJECTIVES: In the present study we investigate the prevalence of the different HBV genotypes in Morocco since no previous careful study has been attempted. METHODS: Epidemiological data from 91 chronically infected patients (45 women and 46 men) were collected prospectively. Sera were tested for anti-HBc IgG, HBeAg, anti-HBe antibody and liver enzymes. Restriction Fragment Length Polymorphism (RFLP) analysis was confirmed by subsequent sequencing of the pre-S and S region of the viral genome in order to determine which HBV genotypes were prevalent among Moroccan patients. RESULTS: The mean age was 41+/-12.4 years. Ten patients (11%) were positive for hepatitis B e antigen (HBeAg) and 81 (89%) were positive for anti-HBe antibodies. By the RLFP method, genotype D, pattern D2, was found in the 77 cases where HBV was successfully amplified. Phylogenetic analysis based on pre-S/S sequences revealed that genotype D in Morocco differed from others D strains subgenotypes (D1, D2, D3 and D4). In addition, the pre-core mutant defined as HBeAg-negative/anti-HBe-positive and HBV DNA positive was detected in 86% of cases. CONCLUSIONS: Our results clearly show that genotype D and pre-core mutant are highly prevalent in Morocco.

New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom.

Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.

Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population.

BACKGROUND: Hereditary hemochromatosis and SERPINA1 mutation were reported to affect liver functions. Our objective was to estimate the prevalence of HFE and SERPINA1 (formerly known as alpha1-antitrypsin, AAT) mutations and assess their influence on hepatocellular carcinoma development. METHODS: This study included 222 controls and 96 cases with hepatocellular carcinoma. PCR-RFLP was used to characterize S and Z alleles in SERPINA1, as well as C282Y/H63D alleles of HFE. RESULTS: In healthy subjects and hepatocellular carcinoma patients as well, no homozygotes for the C282Y mutation were found. In controls, heterozygosity and homozygosity for the H63D mutation were 27 and 0.9%, respectively. Among patients, homozygosity for the H63D mutation was 3.1%, whereas heterozygosity for C282Y and H63D was 2.1 and 35.4%, respectively. Interestingly, albeit it does not reach significance (p=0.062), H63D was more prevalent in hepatocellular carcinoma patients than in controls (38.5 vs. 27.9%, respectively). The association was stronger when considering only male patients with hepatocellular carcinoma (47.1 vs. 23.6, p=0.001). Allele frequencies of S and Z in controls were 0.45% (95% CI=0.2-1.07) and 0.22% (95% CI=0.2-0.6), respectively, and 1 for S and 0% for Z in HCC. No significant difference was found between cases and controls. CONCLUSIONS: We provide a novel appraisal of HFE and SERPINA1 mutations prevalence in the Moroccan population. Results are consistent with the worldwide spread of the H63D and S mutation and the north European restriction of the C282Y and Z. Our results show that H63D carriage is increased among hepatocellular carcinoma patients, suggesting that it may confer an increased susceptibility to hepatocellular carcinoma even in a heterozygous state. On the contrary, HFE C282Y and SERPINA1 mutations do not contribute to hepatocellular carcinoma development.

NPHIs and public goods: a perspective from Morocco.

National Public Health Institutes (NPHIs) provide critical functions that protect and support public health. In Morocco, these functions are divided among three different agencies. Consolidation of these functions into a single agency would encourage a comprehensive approach to public health in Morocco, providing an environment that can support work in new areas of public health (such as chronic diseases), decreasing competition and overlap among agencies, and increasing efficiency. Working together, NPHIs need to develop data and support advocacy so that funding goes not only to the diseases that are in the news and getting attention, but also to those Core Functions that contribute daily to the health and safety of all people.

Genetic polymorphism in the manganese superoxide dismutase gene is associated with an increased risk for hepatocellular carcinoma in HCV-infected Moroccan patients.

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The main risk factors for its development are hepatitis B and C virus infections. Hepatitis B and C viruses induce chronic inflammation and oxidative stress that could predispose a cell to mutagenesis and proliferation. Manganese superoxide dismutase (MnSOD) catalyses the detoxification of free radicals, thus playing a crucial role in the protection against damage. A valine (Val) to alanine (Ala) substitution at amino acid 9, mapping within the mitochondrion-targeting sequence of the MnSOD gene, has been associated with an increased cancer risk. The aim of our study was to investigate a possible association of the Val/Ala-MnSOD polymorphism and HCC development in Moroccan patients. Genotypes were determined by means of PCR and RFLP analysis in 96 patients with HCC and 222 control subjects matched for age, sex, and ethnicity. Homozygous Ala/Ala carriers were 31% in the cases and 18% in the controls, which corresponds to an odds ratio (OR) of 2.89, with a 95% confidence interval (CI) of 1.47-5.68. Stratification into subgroups based on HCV infection status revealed an even more increased risk for homozygous Ala/Ala carriers with hepatitis C infection (38.2% in the cases versus 14.8% in the control subjects OR, 5.09; 95% CI, 1.76-14.66). Our findings provide further evidence of an association between the Ala-9Val MnSOD polymorphism and HCC occurrence in hepatitis C virus-infected Moroccan patients.

Carrier frequencies of mutations/polymorphisms in the connexin 26 gene (GJB2) in the Moroccan population.

Mutations in the Connexin 26 gene (GJB2/Cx26) are responsible for more than half of all cases of prelingual nonsyndromic recessive deafness in Caucasians. The carrier frequency of the 35delG-GJB2 mutation was found to be as high as 2-4% in the Mediterranean populations. Different GJB2 mutations were reported in the Moroccan patients with autosomal recessive nonsyndromic hearing loss; however, rare studies were carried out on the carrier frequencies of these mutations in the healthy populations. The aim of this study was to estimate the carrier frequencies of the GJB2 mutations in the Moroccan population. The molecular analysis of the 35delG mutation and other GJB2 sequence variations was performed in 386 healthy unrelated Moroccan individuals with no known hearing loss. Five GJB2 sequence variations at heterozygous state were found: two mutations, 35delG and 109G > A (V37I), and three polymorphisms, 79G > A (V27I), 341G > A (E114G), and 457G > A (V153I). The carrier frequency of the 35delG mutation was the highest with 2.07% [95% confidence interval (0.90-4.04%)], followed by that of the V37I mutation with 1.43% (0.06-5.39). The carrier frequency of V27I, E114G, and V153I changes was estimated to be 0.71% (0.01-4.34). This finding shows that the 35delG carrier frequency found here is similar to the one observed in Mediterranean populations. It provides new information about GJB2 carrier rates facilitating the diagnosis and the genetic counseling in the Moroccan population.

Absence of GJB3 and GJB6 mutations in Moroccan familial and sporadic patients with autosomal recessive non-syndromic deafness.

UNLABELLED: Deafness is an etiologically heterogeneous trait with a wide variety of genetic and environmental causes. It is generally considered that genetic factors account for at least half of all cases of profound congenital deafness, which can be classified in two categories - dominant or recessive - according to the mode of inheritance and in two types - syndromic or non-syndromic - according to the presence or absence of some other specific clinical features. Mutations in the gene GJB2, encoding the gap junction protein connexion 26, are considered to be responsible for up to 50% of familial cases of autosomal recessive non-syndromic hearing loss and for up to 15-30% of the sporadic cases. It has also been reported that mutations in the GJB6 and GJB3 genes contribute to autosomal recessive and autosomal dominant hearing defects in many populations. OBJECTIVE: The aim of this study was to screen mutations in GJB6 and GJB3 genes in Moroccan patients with autosomal non-syndromic hearing loss. METHODS: We carried out 95 patients with non-syndromic hearing loss. The patients, who were negative for homozygous mutations in GJB2 gene and GJB6-D13S1830 deletion, were tested for the coding regions of GJB6 and GJB3 genes by direct sequencing. RESULTS: No deleterious mutation in GJB6 and GJB3 genes was detected in all deaf patients tested. Only a C357T silent transition in heterozygous state was found in the GJB3 gene in one patient. CONCLUSION: The present data demonstrated that mutations in the GJB6 and GJB3 genes are an infrequent cause of non-syndromic deafness in Morocco.

[Consumption analyze of the antihypertensive drugs in Morocco: period 1991-2005]. / Analyse de la consommation des antihypertenseurs au Maroc: période 1991-2005.

INTRODUCTION: The medical assumption of responsibility of the chronic diseases in Morocco, in particular arterial hypertension, remains problematic. OBJECTIVES: To evaluate the consumption, segmentation and the share of the market of generic antihypertensive drugs during the period: 1991-2005. METHODS: The data were elaborate starting from the declarations of IMS health (Intercontinental Marketing Service) for Morocco. These data related to the sales with only the pharmacies and were expressed as daily defined dose (DDD)/1000 inhabitant-days. RESULTS: The consumption of the antihypertensive drugs increased from 2 to 10 DDD/1000 between 1991 and 2005. The family of diuretics drugs was the most consumed (3.5 DDD/1000) followed by nonassociated beta-blockers (2 DDD/1000) in 2005. The segmentation was primarily represented by the diuretics (34%) and the beta-blockers (20%). The market of generic antihypertensive drugs passed from 3.3% in 1991 to 21.7% in 2005. CONCLUSION: The consumption of the antihypertensive drugs in Morocco remains too low in spite of an increasing tendency to depend especially on the generic drugs.

Microbial quality control of raw ground beef and fresh sausage in Casablanca (Morocco).

In this study, samples of raw ground beef (n = 150) and fresh sausage (n = 100) were collected randomly from butcheries, supermarkets, and fast-food shops, in Casablanca, Morocco. Two types of meat product samples were considered, one with spices (n = 115) and other without spices (n = 135). All the samples were analyzed for the presence of the following bacteria: Escherichia coli, Staphylococcus, Clostridium perfringens, Salmonella, and Listeria monocytogenes. E. coli strains were further typed by pulsed-field gel electrophoresis (PFGE), Operon O, and characterized for virulence genes by polymerase chain reaction (PCR). Results indicated that counts of E. coli, coagulase-positive Staphylococcus, and C. perfringens were 17%, 9.6%, and 8.7% in samples without spices, respectively; and 23.5%, 23.7%, and 29.6% in samples with spices, respectively. Two pathogenic genes, LT and EAST, were identified separately in four strains of E. coli. Salmonella and L. monocytogenes were isolated in 2.8% and 3.2% of the total samples, respectively.

The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population.

AIM: Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population. METHODS: Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR-restriction fragment length polymorphism, confirmed by sequencing. RESULTS: Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3-fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014-5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57-fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4-fold increased risk of HCC (OR, 4.4; 95% CI, 1.18-16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)-positive cases to HCV-positive controls. However, HCV-negative subjects and Pro/Pro genotype had a 3.31-fold increased risk for HCC. CONCLUSION: These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV-negative subjects.

AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men.

AIM: To evaluate for the first time the frequency of Y chromosome microdeletions and the occurrence of the partial deletions of AZFc region in Moroccan men, and to discuss the clinical significance of AZF deletions. METHODS: We screened Y chromosome microdeletions and partial deletions of the AZFc region of a consecutive group of infertile men (n = 149) and controls (100 fertile men, 76 normospermic men). AZFa, AZFb, AZFc and partial deletions of the AZFc region were analyzed by polymerase chain reaction (PCR) according to established protocols. RESULTS: Among the 127 infertile men screened for microdeletion, four subjects were found to have microdeletions: two AZFc deletions and two AZFb+AZFc deletions. All the deletions were found only in azoospermic subjects (4/48, 8.33%). The overall AZFc deletion frequency was low (4/127, 3.15%). AZF microdeletions were not observed in either oligoasthenoteratozoospermia (OATS) or the control. Partial deletions of AZFc (gr/gr) were observed in a total of 7 of the 149 infertile men (4.70%) and 7 partial AZFc deletions (gr/gr) were found in the control group (7/176, 3.98%). In addition, two b2/b3 deletions were identified in two azoospermic subjects (2/149, 1.34%) but not in the control group. CONCLUSION: Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.