Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis.

OBJECTIVE: High concentrations of antituberculosis (anti-TB) drugs can be associated with many adverse drug reactions (ADRs). The objective of this study was to examine the plasma concentrations of rifampicin (RMP) and isoniazid (INH) in patients with and without ADRs. METHODS: Concentration monitoring data of patients treated with anti-TB drugs were retrospectively analyzed from 2009 to 2011. RMP and INH plasma concentrations were measured 2 and 3 h after drug administration respectively using high-performance liquid chromatography. RESULTS: A total of 54 out of 120 patients have experienced ADRs to anti-TB drugs. The median concentrations [interquartile range (IQR)] obtained in patients with and without ADRs were 6.7 mg/l (3.7-9.9) and 5.6 mg/l (2.9-8.6) (p = 0.56) for RMP and 4.3 mg/l (2.3-5.3) and 3.1 mg/l (1.7-4.8) (p = 0.04) for INH, respectively. Related median doses (IQR) were 8.7 mg/kg (8.0-10.0) and 8.6 mg/kg (6.5-9.9) (p = 0.42) for RMP and 4.8 mg/kg (4.3-5.0) and 4.0 mg/kg (2.8-5) (p < 0.01) for INH, respectively. Concentrations above the expected range in patients with and without ADRs were not reached for RMP, but were 76% and 65% for INH, respectively. Correlation between concentrations and doses has not been established for RMP or INH. In addition, high INH concentrations showed no association with sex, age, liver injury or renal or diabetes. CONCLUSIONS: High INH concentrations were common in patients with and without ADRs whereas RMP concentrations were low or within the normal range in most patients. Further studies are required to assess the association between high INH concentrations and the occurrence of ADRs.

[Fatal poisoning in Mali]. / Les intoxications mortelles au Mali.

AIMS: The aim of this study was to determine the epidemiological characteristics of the cases of fatal poisoning in Mali. METHODS: This retrospective study examined the cases of fatal poisoning recorded between 2000 and 2010 in six Health Reference centers, six regional hospitals and three university hospitals in the district of Bamako. RESULTS: During the study period, 146 cases of fatal poisoning were recorded, accounting for 4.6% of all poisoning cases during this period. The average age of patients who died was 24 ± 17.7 years with a female-male ratio of 1.05. Nearly half (43%) were younger than 20 years. The ingestion was intentional in 66.4% of cases, mainly suicide attempts (47%) and therapeutic errors (19%). The median time until arrival at hospital was 8 hours after poisoning with multiple and varied clinical signs. CONCLUSIONS: Decreasing the mortality rate from poison ingestion requires increasing public awareness about poisons and improving emergency service equipment and health personnel training.

Cardiac involvement and its complications about three cases of severe scorpion envenomation.

For several decades, Morocco is confronted to medico-social problem of scorpion stings and envenomations. In 2009, epidemiological data established by the Poison Control Center recorded 29,816 stung patients, with an incidence of 1.1‰ and a fatality rate of 0.18%. The neurotoxins from scorpion venom are potent activators of the autonomic nervous system resulting a physiopathological disorder of vital systems. The most serious clinical manifestations are neurotoxic effects, pulmonary edema and cardiovascular distress. This present work reports the cases of three children (4 years and 6 months, 8 months and 15 days, 4 years), hospitalized in intensive care for an envenomation by Androctonus mauritanicus (the most fatal scorpion specie). The children presented cardiac dysfunction where pulmonary edema and state of shock were complications resultants. Two cases survived after supportive and symptomatic treatment based on dobutamine as primordial treatment in cardiovascular and pulmonary correction and other drugs. The third case died. The objective of this work was to detect the limit of the effectiveness of symptomatic treatment during a severe scorpion envenomation.

Prognostic factors of Atractylis gummifera L. poisoning, Morocco.

In Morocco, acute Atractylis gummifera L. poisoning represents the leading cause of death by plant poisoning especially for children. All cases received in the Moroccan poison control centre from January 1981 to December 2009 (n = 467) were included in a retrospective study of the characteristics and risk factors of A. gummifera L. poisoning. The most vulnerable age group was children (63.4% of cases). Most cases were due to accidental exposure (75.5%), but some were from therapeutic use (18.1%) or attempted abortion (7.4%). Patients presented with moderate poison severity signs (grade 2) in 22.3% of cases or severe signs (grade 3) in 21.0%. The mortality rate was 39.2%. The majority of deaths (81.1%) occurred in children aged < 15 years following accidental exposure. Multivariate logistic regression analysis revealed that risk factors for mortality were coma (OR = 20.5); hepatitis (OR = 52.7) and rural residence (OR = 7.26), while gastric decontamination was a protector factor (OR = 0.26).

[Ophidian envenomation in the region Souss-Massa-Drâa in Morocco]. / Les envenimations ophidiennes dans la région de Souss-Massa-Drâa au Maroc.

The present study aims to determine the main characteristics of ophidian envenomation in the Souss-Massa-Drâa region in Morocco. It consisted of a descriptive retrospective analysis of all snakebite cases recorded by the Moroccan Poison Control and Pharmacovigilance Center, from 1980 to 2008. According to reported data, this region is the most affected in Morocco with 479 cases, that is 27.6% (17 cases/year). The average age of victims was 26.07 ± 18.28 years. The patients developed clinical signs (55%) dominated by disorders of the digestive system (35.5%), cardiovascular diseases (21.4%), and heart rhythm disorders (16.8%). The lethality and sequelae rates were 12% and 1.9%, respectively.

[Epidemiology of snakebites in Morocco]. / Epidémiologie des envenimations ophidiennes au Maroc.

This study was based on a retrospective descriptive analysis of all cases of snakebite recorded at the Poison Control and Pharmacovigilance Center of Morocco from 1980 to 2008. A total of 1,761 snakebites, i.e., 61 cases per year, were observed during the study period. Males accounted for 54.5% of victims (sex ratio (M/F) = 1.2) and 70% of cases occurred in rural areas. The average age of snakebite victims was 26.7 +/- 17.5 years. A seasonal snakebite peak was observed between May and August coinciding with the warmest period of the year, harvest time and snake migration. Sixty-two percent of patients presented clinical symptoms including respiratory, cardiovascular, gastrointestinal, neurological and mucocutaneous signs. The average fatality rate was 7.2% per year and the sequel rate was up to 1.04%. This study demonstrates that management of snakebite is problematic in Morocco. Morbidity was probably underestimated. Restricted access to antivenom is a major problem in rural areas where the population cannot afford the cost.

[Poisoning by Atractylis gummifera L. Morocco poison control center data]. / Intoxication par Atractylis gummifera L. Données du centre antipoison et de pharmacovigilance du Maroc.

To assess the extent and severity of poisoning by Atractylis gummifera L. in Morocco, a descriptive retrospective study was conducted on all the poisoning cases listed between 1981 and 2004 to the Morocco Poison Control Center. During this period, 240 people were hospitalized for glue thistle poisoning, 72% of which are children under 16 years. The severity of the poisoning has been affirmed by significant intrahospital lethality. Indeed, among the 182 patients for whom the outcomes were known, 98 died (54%).

[Scorpion envenomation treated at Beni Mellal Provincial Hospital in Morocco]. / Les envenimations scorpioniques a l'hôpital provincial de Beni Mellal (Maroc).

The Beni Mellal province has one of the highest incidences of scorpion envenomation in Morocco. The purpose of this retrospective study was to report and analyze data recorded in scorpion envenomation victims admitted to the intensive care department of the Beni Mellal Provincial Hospital. A total of 63 patients were admitted in 2005. Most stings occurred during summer mainly in June and July. Most (60.3%) occurred at night between 6 p.m. and 6 a.m. Most patients were children younger than 16 years (mean, 10.2 +/- 12.9 years). At the time of admission, general manifestations of envenomation were present in 72.6% of patients and life-threatening symptoms were observed in 27.4%. Therapy consisted of symptomatic treatment and in-hospital mortality was 28.6%. There was not a significant difference in mortality in function of age or severity of manifestations at the time of admission.

Prevalence and preventability of adverse drug events in a teaching hospital: a cross-sectional study.

We determined the prevalence of adverse drug events (ADEs) in a general teaching hospital in Rabat, Morocco. We performed a 5-day cross-sectional study of hospital departments recruiting inpatients and outpatients. Among the 1390 patients surveyed, 59 (4.2%) experienced at least 1 ADE and for 20 patients (1.4%) the ADE was responsible for hospitalization or prolongation of hospitalization. The ADE was classified as serious in 28 patients. Of the total of 76 ADEs, 10 (13.2%) were categorized as preventable; 6 of these occurred during the treatment monitoring phase. Patients who experienced an ADE were more likely to be women, to be younger (< 30 years) and to be hospitalized in medical departments.

Prevalence and preventability of adverse drug events in a teaching hospital: a cross-sectional study

We determined the prevalence of adverse drug events [ADEs] in a general teaching hospital in Rabat, Morocco. We performed a 5-day cross-sectional study of hospital departments recruiting inpatients and outpatients. Among the 1390 patients surveyed, 59 [4.2%] experienced at least 1 ADE and for 20 patients [1.4%] the ADE was responsible for hospitalization or prolongation of hospitalization. The ADE was classified as serious in 28 patients. Of the total of 76 ADEs, 10 [13.2%] were categorized as preventable; 6 of these occurred during the treatment monitoring phase. Patients who experienced an ADE were more likely to be women, to be younger [< 30 years] and to be hospitalized in medical departments

Risk factors for scorpion stings in the beni mellal province of morocco

Scorpion stings comprise a serious problem throughout the globe, especially in regions where they are more frequent. In Morocco, Beni Mellal is one of the provinces most affected by this burden. This study aimed to trace the epidemiological profile of scorpion stings in Beni Mellal in order to improve patient care and prevent both morbidity and mortality. Our work is a retrospective study of scorpion stings based on medical charts of Beni Mellal. From 2002 to 2007, 8,340 cases were registered in this province with an average incidence of 1.36‰. The stings were more frequent in summer months, particularly July and August, and between 6 p.m. and 6 a.m. (59.8 percent). The average age of victims was 26.54 ± 18.42 years. Children were affected in 30.3 percent of the cases. Of all registered cases, 67.3 percent of the patients received medical aid in less than an hour after the sting. The envenomation rate (Class II and Class III) was 12.4 percent and the overall case-fatality rate was 0.42 percent with a mortality rate of 0.005‰. Statistical analysis of the various studied factors revealed a significant connection among the envenomation class, patient age and evolution.(AU)

Determination of the acetylator phenotype in Moroccan tuberculosis patients using isoniazid as metabolic probe.

A large interindividual variability in drug acetylation is associated with genetic polymorphism of the polymorphic Type 2 N-acetyltransferase (NAT2), and an important interethnic difference has been frequently observed. However, few data on this polymorphism in the Moroccan population are available. In the present study the acetylator phenotype in 89 Moroccan patients with tuberculosis has been determined using isoniazid (INH) as metabolic probe. The subjects (69 women and 20 men between 18 and 77) were each given a 5 mg/kg oral dose of INH. Plasma concentration of INH and its metabolite, acetylisoniazid (ac.INH), were measured by high-performance liquid chromatography at 3 hours post dose. The plasma level ratio of acetylisoniazid to isoniazid (Rm), and the plasma level of acetylisoniazid as a percentage (%ac.INH) were used to express the activity of the polymorphic NAT2. The distribution of these 2 parameters in the studied population was clearly bimodal resulting in 2 distinct groups: slow acetylators (Rm < or = 0.84, %ac.INH < or = 45.64%), and fast acetylators (Rm > or = 1.29, %ac.INH > or = 56.26%) who accounted respectively for 61.8% and 38.2% of the population. The 2 approaches used showed a complete concordance.

Ochratoxin A in human plasma in Morocco: a preliminary survey.

Available epidemiological information seems to indicate that Balkan endemic nephropathy is associated with consumption patterns involving foodstuffs contaminated with ochratoxin A (OTA) and with a higher frequency of OTA-positive blood samples. The aim of this preliminary study was to assess OTA concentrations in human plasma in Morocco. Therefore, samples from 309 healthy volunteers (213 males, 96 females) were analysed. The analyses revealed that 60% of the human plasma sampled was positive for OTA (61.5% in the male and 56% in the female population), and an average concentration of 0.29 ng/mL (0.31 ng/mL in males, 0.26 ng/mL in females). The highest concentration found was 6.59 ng/mL. The results suggest that the Moroccan population is exposed to OTA, even though the OTA plasma levels are lower than that reported in some North African countries.

Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection.

Simultaneous measurement of isoniazid and its main acetylated metabolite acetylisoniazid in human plasma is realized by high-performance liquid chromatography. The technique used is evaluated by a factorial design of validation that proved to be convenient for routine drug monitoring. Plasma samples are deproteinized by trichloroacetic acid and then the analytes are separated on a microBondapak C18 column (Waters). Nicotinamide is used as an internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)-acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm. The validation, using the factorial design allows one to: (a) test the systematic factors of bias (linearity and matrix effect); (b) estimate the relative standard deviations (RSDs) related to extraction, measure and sessions assay. The linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00% and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD Ac.INH=15.86%). The method is also selective in cases of polytherapy as many drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The matrix effect (plasma vs. water) is negligible for INH (3%), but statistically significant for Ac.INH (11%). The application of this validation design gave us the possibility to set up an easy and suitable method for INH therapeutic monitoring.

[Atractylis gummifera L. poisoning: a case report]. / L'intoxication par le chardon à glu (Atractylis gummifera L.); à propos d'un cas clinique.

Intoxication by Atractylis gummifera L. frequently happens in Morocco. It's often accidental and mortal if no precocious and effective treatment. In order to take stock of this intoxication of which diagnosis is clinical and treatment symptomatic, we suggest to analyze one clinical case of the intoxication by Atractylis gummifera L. on a 12 year old child who accidentally ingested this plant.

Ochratoxin A in beverages from Morocco: a preliminary survey.

In a preliminary study, samples of Moroccan wines (n = 30), beers (n = 5) and fruit juices (n = 14) were assayed for ochratoxin A (OTA) by HPLC with fluorimetric detection, followed by confirmation by cleavage of the OTA molecule using carboxypeptidase with HPLC-fluorimetric determination of ochratoxin alpha (OT alpha). All the wine samples were contaminated, and the overall median OTA concentration was 0.65 microg/l (range 0.028-3.24 microg/l). One of the 14 samples of fruit juices was contaminated with a concentration of 1.16 microg/l, whereas none of the five beer samples was contaminated. This is the first report on the occurrence of OTA in various beverages from Morocco.

Blood cadmium concentration in the population of the Rabat area, Morocco.

Blood cadmium concentrations were determined in 377 adults, 297 men and 80 women, randomly selected from the Rabat Transfusion Center, Morocco. The mean blood cadmium level was 1.1+/-0.7 microg/l, which was higher than in French subjects, with an average of 0.7+/-0.6 microg/l. In Moroccan people, the mean blood cadmium concentration of men, 1.1+/-0.8 microg/l, was significantly higher than that of women, 0.8+/-0.4 microg/l, whereas in the French people tested, there was no statistically significant difference between men and women. In Morocco, employment of men and the smoking habits of men and women were linked to an increase of blood cadmium levels. The significantly higher level observed in men could be due to a higher percentage of men who were smokers and to professional activity leading to increased exposure to cadmium.

A comparison study of two therapeutic protocols for neurosyphilis.

In Morocco, neurosyphilis is a serious public health problem. In the neurology service at the specialist hospital in Rabat, two drug treatments were used. Treatment A consisted of infusion over a period of 4 h of 20 MUI of penicillin G per day for 3 weeks. Treatment B consisted of infusion over a period of 6 h of 30 MUI of penicillin G per day for 10 days. Each treatment was tested on a group of eight neurosyphilitic patients as first-line treatment. On the first day of treatment, both blood and CSF pharmacokinetics were sampled for each patient. Blood and CSF were taken within 24 h. Penicillin G concentrations were determined by a microbiological method. The results obtained showed that perfusions of either 20 MUI or 30 MUI of penicillin allowed the achievement of high serum concentrations. These increased progressively until reaching their maximum at T4 h for treatment A (from 92.33 to 106.38 micrograms/ml). For treatment B, maximal concentration is obtained at T6 h (from 108 to 141.52 micrograms/ml). Penicillin concentrations decreased immediately after stopping the perfusion. At CSF levels, penicillin G concentrations were identical to serum concentrations. However, one difference was observed: a one-hour difference between the serum and CSF peaks. The CSF peak was achieved at T5 h for treatment A (0.063 to 2.25 micrograms/ml) and at T7 h for treatment B (0.92 to 2.94 micrograms/ml). The concentrations obtained were largely superior to the CMI of Treponema pallidum for both treatment A and treatment B, at 47 times and 82 times higher respectively. The recovery time of the patients was 14 h for treatment A and 24 h for B treatment. These results have shown that therapeutic method B was more efficient than A. Moreover, the evolution of penicillin G's diffusion in the CSF during treatment, of cell counts of protein level, of the VDRL test and of the gamma-globulin rate was studied.