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Biomedical subjects

F Doua

Publications and source records attributed to F Doua.

At least 37 records · Page 2Linked to original sources
PubMed1996

The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis.

Fifty-eight patients in the early-late stage (early central nervous system involvement) of Trypanosoma brucei gambiense trypanosomiasis were treated with pentamidine and divided into four groups (G1, G2, G3, and G4) according to cerebrospinal fluid (CSF) indicators: white blood cell (WBC) count, protein level (CSF protein), and the presence or absence of trypanosomes. Group G1 consisted of eight patients with normal CSF WBC counts and CSF protein levels and trypanosomes in the CSF. Group G2 consisted of nine patients with elevated CSF WBC counts, normal level of CSF protein, and trypanosomes in the CSF. Group G3 consisted of 31 patients with high CSF WBC counts, normal CSF protein levels, but no trypanosomes in the CSF. Group G4 consisted of 10 patients with normal CSF WBC counts and CSF protein levels and trypanosomes demonstrated by CSF culture. Post-treatment follow-up of all patients for at least one year revealed three relapses. There were two deaths from diseases unrelated to trypanosomiasis or to the treatment protocol. Of these patients, 52 were followed for more than two years, the time necessary to confirm a complete cure, indicating a cure rate of 94%. Pentamidine is therefore effective in treating the early-late stage of T. b. gambiense trypanosomiasis, and is comparable with melarsoprol or eflornithine in terms of its tolerance and availability.

Adolescent↗
PubMed1995

Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness.

1. Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg-1 pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2. Maximum plasma drug concentrations varied between 713 and 2461 nmol 1-1. After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3. The 'terminal' elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) ml min-1 and 265 (107-446) h, respectively). The median apparent volume of distribution (Vss) was 11,850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4. Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5. The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day.

Adult↗
PubMed1995

Twenty-four-hour plasma cortisol and prolactin in human African trypanosomiasis patients and healthy African controls.

We have previously demonstrated that human African trypanosomiasis (sleeping sickness) at the stage of meningoencephalitis results in a major disruption of the circadian rhythmicity of sleep and wakefulness that is proportional to the severity of the disease. This paper examines the corresponding 24-hourly secretion in cortisol and prolactin and compares it with the hourly distribution of sleep composition in infected patients and healthy African subjects. The secretion of cortisol in humans follows a circadian rhythm relatively independent of the sleep-wake cycle, whereas that of prolactin exhibits fluctuations over the 24-hr day that are strongly related to the sleep-wake cycle. After the clinical classification of the patients according to the severity of the disease, hourly blood samples were taken over 24 hr via an indwelling catheter. Plasma cortisol and prolactin were analyzed by radioimmunoassay, and the variations in the hourly concentrations were analyzed for the presence of a potential 24-hr rhythm (circadian). All of the healthy African subjects showed significant circadian rhythms in both cortisol and prolactin secretion, similar to data on humans from temperate regions, and a sleep-related anamnestic afternoon peak of prolactin. Major disruptions in the circadian rhythms of plasma cortisol and prolactin were found in the three patients with the most severe illness, in contrast to the four who were less severely ill and the healthy controls. Thus, it appears that as the disease progresses in severity, major disruptions begin to occur in body circadian rhythms, not only in the sleep-wake cycle as reported elsewhere, but also in cortisol and prolactin secretion, suggesting that sleeping sickness affects the circadian timing system.

Adolescent↗
PubMed1994

[The detection of anti-galactocerebroside autoantibodies in human African trypanosomiasis].

The pathogenesis of the central nervous system (CNS) damage in human african trypanosomiasis (HAT) is unknown. In view of an immunological mechanism, as in another trypanosomiasis, Chagas' disease, the causative agent of which is Trypanosoma cruzi, we have searched autoantibodies directed against glycosphingolipids of CNS. Detection and characterization of autoantibodies were performed by ELISA and detection after thin-layer chromatography of glycolipids with sera of an experimental model of HAT in sheep and sera of patients suffering of HAT from Côte d'Ivoire and Congo. The predominant reactivity of these sera, was characterized with galactocerebrosides, the major glycolipids of the myelin. Autoantibodies were detected in 42.8% and 25% of patients' sera, respectively from Côte d'Ivoire and Congo. The proportion of these antibodies increased dramatically to 72% in sera of patients with neurological symptoms. Anti-galactocerebroside antibodies were also found in CSF of 24.4% of Congolense patients. The pathogenic significance of these anti-galactocerebroside antibodies remains to be determined. They may constitute a predicative marker for the neurological improvement in HAT.

Animals↗
PubMed1994

[Current therapy of trypanosomiasis].

The authors review the available products used for human african trypanosomiasis (HAT) chemotherapy: pentamidine, suramin, melarsoprol and the new compound DFMO. The administration of pentamidine at the beginning of the nervous stage, when the number of cells in the cerebrospinal fluid do not exceed 20/mn3 is a new approach for HAT treatment. At this time of the disease, patients generally are healthy and the pentamidine therapy avoids the use of the toxic melarsoprol (Arsobal). An alternative protocol for Arsobal therapy (2, 16 mg/kg/d for 10 consecutive days) has been described from pharmacokinetics data to decrease the rate of relapses and the duration of hospital care. Efficacy and tolerance of this new protocol must be evaluated by randomised clinical trials. Preliminary data of clinical trials using short-term DFMO therapy are encouraging. DFMO therapy be less expensive. From its efficacy and tolerance, DFMO is a choice chemotherapy for HAT treatment, especially in the case of resistance to usual trypanocides. Both MLD 73811 and IMOL 881 are new trypanocidal compounds, effective on Trypanosoma brucei rhodesiense and T. b. gambiense. In addition, IMOL 881 is effective on the animal trypanosomes, T. evansi and T. equiperdum. Waiting for the availability of these new products, classical trypanocides remain the basis of HAT treatment.

Adenosylmethionine Decarboxylase↗
PubMed1994

[The distribution of sleep and wakefulness in human African trypanosomiasis].

Last century, patients with human African trypanosomiasis were described as sleepy by day and restless by night, and physicians referred to this condition as sleeping sickness. Such a description could have evoked a disturbance of circadian rhythms. However, it is only in 1989 that the first 24-hour recording was performed by our team in Niamey (Niger) in a patient with sleeping sickness. The patient was a Niger-born farm worker who had contracted the disease near Gagnoa (Côte d'Ivoire). Polysomnographic recordings (electroencephalogram, EEG, electrooculogram, electromyogram, electrocardiogram, buccal and nasal airflow, and chest respiratory movements) showed a disappearance of the circadian distribution of sleep and wakefulness, which tended to occur evenly throughout day and night, with a sleep-wake alternation of approximately 80 minutes. Two investigations were conducted thereafter. The first one was done at Daloa (Côte d'Ivoire) in 8 patients who were recorded during two 24-hour periods, with and without hourly blood samples; the second at Brazzaville (Congo) in 10 patients recorded for 24 hours before and after treatment with melarsoprol. All patients were at the stage of early meningoencephalitis. At Daloa, polysomnographic recordings were taken on two 8-channel EEG machines (Alvar Minihuit, and T3-ECEM), as well as on a portable Oxford Medilog 9000 system from the same electrodes. Sleep and wake structure was altered in the most severely sick patient, the EEG trace being loaded with slow waves. Stages 1 and 2, and stages 3 and 4 could not be distinguished from one another. In the other patients, all sleep stages were easily scored. No difference was seen between recordings, regarding blood collection.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗
PubMed1994

Disruptions in the secretion of cortisol, prolactin, and certain cytokines in human African trypanosomiasis patients.

It has been shown previously that sleeping sickness at the stage of meningoencephalitis manifests itself as a significant disturbance in the circadian rhythm of sleep-wakefulness. The objective of the current study was to examine the extent of circadian disruption in infected patients by measuring 24 hours patterns of plasma cortisol, an example of a classical circadian rhythm relatively independent of sleep, and prolactin, a primarily sleep-related rhythm. Plasma levels of certain cytokines were also measured to examine the immunopathogenesis of human African trypanosomiasis. An attempt was made to relate any circadian disruptions to the severity of the disease. The three most advanced patients demonstrated circadian disruptions in cortisol, prolactin and sleep-wake rhythms. The prime cytokine factor that correlated with the progression of the disease in humans was interferon-gamma, levels being 7- to 12-fold higher in the patients without any circadian rhythms. Our findings support the hypothesis that human African trypanosomiasis induces selective changes in the suprachiasmatic nucleus, important as a pacemaker for biological rhythms, resulting in disruptions of circadian rhythmicity in advanced stages of the disease.

Adolescent↗
PubMed1994

[Evaluation of the parasitologic technics used in the diagnosis of human Trypanosoma gambiense trypanosomiasis in the Ivory Coast].

The investigators carried out a comparative evaluation of twelve or parasitological techniques used nowadays in the diagnosis of human trypanosomiasis and parasite isolation in the lymph fluid, blood and cerebro-spinal fluid (CSF). The tests were performed on 64 seropositive suspects selected with TESTRYP-CATT among 661 attendants examined at the Projet de Recherches Cliniques sur la Trypanosomiase (PRCT), Daloa, Côte-d'Ivoire. The study showed that the sensitivity of the different techniques varies between 17.2% (for CSF inoculation to Mastomys) and 84.5% (for the anion exchange centrifugation technique-mAECT). The classical techniques, says lymph fluid examination, direct blood examination and thick blood have a sensitivity of 58.6, 22.4 and 34.5% respectively. The most sensitive methods are lymph fluid examination, mAECT and double centrifugation of CSF (69%). The sensitivity increases up to 98.3% with the combination of two or three techniques. The combination of lymph fluid examination/mAECT/double centrifugation of CSF is either the most sensitive and the most suitable one for use in the field. The combination of lymph fluid examination and mAECT which detects 91.4% of the infected subjects is the most efficient. The authors discussed the results and recommended that similar study be done in field conditions to assess methods which either demonstrated better sensitivity and are more suitable for field use.

Animals↗
PubMed1993

Human trypanosomiasis in the Ivory Coast: therapy and problems.

Human African trypanosomiasis (sleeping sickness) caused by Trypanosoma gambiense is recrudescing alarmingly in the Ivory Coast. Between 1987 and 1992, 980 new cases were registered. In the Bouafle District alone, 214 new cases were diagnosed in 1992, with a prevalence reaching 7% in some villages. This situation is a consequence of the neglect of control activities over the last five years. The problems linked with treatment of sleeping sickness in 626 patients, using three drugs, are described. The side-effects vary in severity according to the drug used. Out of 350 patients treated with melarsoprol (ARSOBAL), 4% developed encephalopathy, 5.7% died during treatment, 2% of encephalopathy. Relapses were noted in 3.7% of patients between 3 and 20 months after treatment. Among 150 patients treated with pentamidine, one case of diabetes mellitus was observed. The patient died of this complication 24 months after treatment. 2% relapses or reinfections were registered after pentamidine treatment. The most frequently encountered side-effects during intravenous plus oral treatment with DFMO were diarrhoea (64.4%) and anemia (35.5%). This drug was just as effective and better tolerated when treatment was limited to 14 days and administered intravenously only.

Animals↗
PubMed1993

Sleep-wake cycle in human African trypanosomiasis.

Sleeping sickness patients are classically described as sleepy by day and restless by night. Prior to this study, we had objectively confirmed this description by recording 24-h sleep patterns in a patient with human African trypanosomiasis. We report 24-h polysomnographic recordings (EEG, electrooculogram, electromyogram, electrocardiogram, and nasal, buccal, and thoracic respiratory traces) performed on two eight-channel electroencephalographs in eight patients with untreated sleeping sickness at an early stage of meningoencephalitis. As in our previously reported patient, there was no hypersomnia. The patients presented mainly a disorganization of the circadian alternation of sleeping and waking, with no or little alteration in the states of vigilance at this early stage of the disease. The disorganization was proportional to the degree of severity of the clinical symptoms. It may be due to an alteration in biological clock mechanisms.

Adolescent↗
PubMed1992

Survival of Trypanosoma brucei brucei in cerebrospinal fluid.

Different compositions of artificial cerebrospinal fluid (CSF) and the CSF from sleeping sickness patients both with and without late-stage [i.e. central nervous system (CNS)] involvement were evaluated for their abilities to support survival of Trypanosoma brucei brucei. Artificial CSF, containing the major electrolytes, amino acids and carbohydrate components of healthy fluid, was equivalent to the CSF from patients without CNS involvement (survival time 20 hours). Normal CSF does not therefore contain substances which deter the parasite. The CSF from the late-stage patients did not support survival for longer than 10 hours, probably because it contained increased numbers of lymphocytes and antibodies.

Animals↗
PubMed1992

Human African trypanosomiasis: presence of antibodies to galactocerebrosides.

Improvements were made in the immunodetection of anti-galactocerebroside (anti-GalC) antibody in sera of patients with human African trypanosomiasis by thin-layer chromatography, enzyme-linked immunosorbent assay, and immunoadsorption. Rabbit anti-GalC antibodies were used to standardize these techniques and demonstrate their specificity. Anti-GalC antibodies were found in the sera of 42.8% of 63 patients with human African trypanosomiasis. Thirty-four control subjects living in the same endemic area were also tested. Anti-GalC levels were higher in human African trypanosomiasis patients with neurologic disturbances compared with patients without such disturbances. These antibodies were distributed mainly between the IgG and IgM classes, but 28% of the patients with human African trypanosomiasis had increased IgA levels without anti-GalC antibody activity.

Agglutination Tests↗
PubMed1992

Study of evoked potentials in human African trypanosomiasis.

Human African trypanosomiasis or sleeping sickness has a stage of neurological involvement characterized by the onset of diffuse meningoencephalitis with sleep disturbances and decreased wakefulness. The pathogenesis of this disease is not well understood. We studied auditory, visual, sensory, and motor evoked potentials in 16 patients with trypanosomiasis in the early stage of meningoencephalitis. In all patients, the brain-stem auditory evoked response (BAER) and the pattern-reversal visual evoked response (PVER) were normal. On the other hand, abnormalities of the somatosensory evoked response (SSER) or the motor evoked response (MER) were found in only five cases; however, their relationship to the illness could not be definitely confirmed. The study results indicate that the evaluated pathways were essentially intact, in particular at the level of the brain-stem in the early stage of the disease. Sleep disturbances and decreased wakefulness noted at this stage were thus linked more closely to functional involvement at the level of the sleep centres than to any detectable specific anatomic lesion.

Adolescent↗
PubMed1991

[Evaluation of Testryp CATT applied to blood samples on filter paper and on diluted blood in a focus of trypanosomiasis due to Trypanosoma brucei gambiense in the Ivory Coast].

The Testryp CATT was performed on dried blood samples on filter-paper and on diluted blood using a microtechnique. This method was applied to both sample collection techniques and was evaluated in parallel with the classical Testryp CATT on whole blood, as described in the instructions provided with the reagents by the manufacturer. A total of 2087 people were tested; 453 samples were tested in the laboratory and 1634 during a field survey in 5 villages of a trypanosomiasis focus in Daloa, Côte d'Ivoire. This study has demonstrated that the Testryp CATT micromethod on either type of sample collection gives results comparable to the Testryp CATT on whole blood. The collection of dried blood samples on filter-paper can be performed by non-specialized staff in trypanosomiasis control programmes of the national health services. In addition, a flask of CATT reagent will allow testing of 6 times more people by the micromethod than by the classical whole-blood method. The micromethod is suitable in the implementation of programmes for the serological surveillance of populations at risk.

Agglutination Tests↗
PubMed1990

Effects of Mel B arsobal and alpha-difluoromethylornithine on the awakening electroencephalogram of humans with gambiense trypanosomiasis disease: preliminary report.

Five males and three females, at the encephalic stage of sleeping sickness, were submitted to trypanocide therapies. Three of the patients were treated with the Mel B Arsobal drug, the five others with difluoromethylornithine, using different protocols. Awakening electroencephalographic data were obtained prior to treatment and, at regular intervals, during and after treatment. Prior to treatment the awakening tracings showed important abnormalities (slow delta waves were superimposed on theta background rhythms). During treatment (except in one patient treated with Arsobal) recordings returned gradually to fast rhythms and several days after therapy, tracings returned to the normal awakening patterns. The use of the awakening electroencephalogram as a tool to test effects of curative drugs in the sleeping sickness syndrome is discussed.

Adolescent↗
PubMed1990

[Circadian analysis of sleep, rectal temperature and immunological and endocrinological variables in sleeping sickness: preliminary study].

A multidisciplinary study was conducted in 8 patients with neurological Human African Trypanosomiasis. The sleep-wake cycle followed an ultradian pattern which was more pronounced in patients with more severe symptoms. The EEG trace was consistently interrupted by numerous cyclic activation patterns with K complexes, rapid low amplitude elements and slow high voltage elements. Circadian rhythmicity was also disturbed in other physiological (rectal temperature), immunological (interleukins) or hormonal (cortisol, prolactin) variables, the disturbance being greater in severely hit patients.

Adolescent↗