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F Doua

Publications and source records attributed to F Doua.

50 records · Page 3Linked to original sources

[The different present-day clinical picture of human African trypanosomiasis caused by T. b. gambiense. Analysis of 300 cases from a focus in Daloa, Ivory Coast].

300 patients with sleeping sickness have been admitted, at the AHT clinic of Daloa, over a time period of 22 months. The sex ratio of the patients is 1.5 males for 1 female; the mean age is 25.5 years. The most frequent signs and symptoms observed by clinical examination are: fever (30%), nodes (86.3%), prurigo (43.3%), splenomegaly (15.3%), hepatomegaly (1%), headache (72.6%), vigilance and sleeping disturbances (68.7%), perioral reflexes (67.6%), cheiro-oral reflexes (64.3%), movement disorders consisting of tremor, choreo-athetosis movements, buccal dyskinesia or seizures (35%), motor palsy and gait disorders (15%), tonus disturbances (12.3%), sensitivity abnormalities (17%), endocrine disorders (16.3%), psychiatric symptoms (6.3%). According to CSF status, 261 patients have been classified in second period (P2). This group, although biologically well defined, is in fact a miscellaneous group of clinical signs and symptoms ranging from apparently normal patients to sleeping comatose and cachectic patients. 93% of the patients in this group have peripheral signs associated with neurological symptoms. They are as frequent in the first period as in the second period, with a statistical significance. This is an argument to think that the CNS is early affected in the course of the disease. The classification of the patients in groups of increasing neurological impairments, is in accordance with this hypothesis. 89% of the patients in the second period have only slight neurological signs. This explain how difficult it is for a physician to use melarsoprol in the treatment of all patients classified in second period.

Adolescent↗

ELISA assay for melarsoprol.

A sensitive ELISA method has been developed for measuring the trypanocidal drug melarsoprol. The test allows for the detection of the drug in human sera and in cerebrospinal fluid at the ng/ml level. Preliminary analyses on patient sera and CSF confirm the feasibility of the method. Further application of the test will enable to conduct the necessary pharmacokinetic and metabolic studies; the drug monitoring should hopefully result in improved treatment schedules minimizing the undesired side effects, e.g. lethal encephalopathies.

Arsenicals↗

Treatment of human late stage gambiense trypanosomiasis with alpha-difluoromethylornithine (eflornithine): efficacy and tolerance in 14 cases in Côte d'Ivoire.

alpha-Difluoromethylornithine (DFMO; eflornithine), an inhibitor of polyamine biosynthesis, was used to treat 14 patients with late stage gambiense sleeping sickness, 12 cases having been previously treated with and considered refractory to melarsoprol. alpha-Difluoromethylornithine was administered intravenously at a dose of 400 mg/kg/day for 14 days followed by oral treatment, 300 mg/kg/day, for 21-28 days. In all patients treatment was associated with rapid disappearance of trypanosomes from body fluids (in several cases within 24 hr) and decreased cerebrospinal fluid white blood cell counts. In all but one patient, who died of a pulmonary infection during treatment, alpha-difluoromethylornithine produced a dramatic reversal of clinical signs and symptoms of the disease. Determination of drug concentrations in serum and cerebrospinal fluid of 5 patients demonstrated that alpha-difluoromethylornithine diffuses into the central nervous system with cerebrospinal fluid levels representing up to 51% of corresponding serum concentrations. Diarrhea, abdominal pain, and anemia were the most frequent side effects associated with therapy, but were reversible and did not necessitate discontinuation of treatment. Four patients have been followed for more than 2 years post-treatment without evidence of relapse.

Administration, Oral↗

The somnogenic T lymphocyte suppressor prostaglandin D2 is selectively elevated in cerebrospinal fluid of advanced sleeping sickness patients.

To help to elucidate the changes induced by Trypanosoma brucei gambiense in the central nervous system (CNS) in advanced sleeping sickness patients, levels of interleukin-1 (IL-1) and prostaglandins D2 (PGD2) and E2 (PGE2) were measured by radioimmunoassay in the cerebrospinal fluid (CSF) from 24 patients diagnosed on the criteria of CSF protein, leucocyte count and parasite presence as having CNS (i.e. late stage) involvement, and from 12 patients without CNS involvement. PGD2 concentrations were selectively and markedly elevated in the late stage patients. The increased PGD2 may in part account for the increased somnolence and the immunosuppression within the CNS. Measurement of PGD2 levels in CSF may be a useful criterion for CNS involvement.

Adolescent↗

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid during treatment of Trypanosoma gambiense infection in Côte d'Ivoire.

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid (CSF) were determined in 11 patients with Trypanosoma gambiense infection without involvement of the central nervous system in Côte d'Ivoire. Blood samples were drawn during a 48 h period after the first and last dose of pentamidine dimesylate given as 10 intramuscular injections on alternate days. Maximum plasma concentrations were generally attained within one hour after injection but varied extensively (420-13420 nmol/litre). The median plasma concentration 48 h after the last dose was approximately 5 times higher than that after the first dose. The ratio between whole blood and plasma concentration was approximately 2. Small amounts of the drug were found in the CSF after the last dose. The findings showed inter-individual differences in the pharmacokinetics of pentamidine. The currently recommended daily dose regimen could be questioned, as drug accumulation was pronounced. All patients were cured and the concentrations attained should be considered as parasiticidal. Further studies on the kinetics and distribution after single and multiple doses of pentamidine as well as studies on the possible relationship between adverse effects and plasma concentrations are, however, needed.

Adolescent↗

Diagnosis of Trypanosoma brucei gambiense sleeping sickness using an antigen detection enzyme-linked immunosorbent assay.

A monoclonal antibody-based enzyme-linked immunosorbent assay (antigen ELISA) developed for detection of trypanosome antigens in the serum and cerebrospinal fluid (CSF) of patients as a means for diagnosis of Trypanosoma brucei gambiense sleeping sickness was evaluated at the Bureau Central de la Trypanosomiase, Kinshasa, Zaire. Sixty-nine (89.6%) of 77 parasitologically confirmed cases examined at the Daloa clinic had antigens in serum; 35 (45.5%) had antigens in CSF and, in 4 of these, the antigens were detected in CSF only. Taking the serum and CSF results together, 73 (94.8%) of the 77 patients were positive in the assay. In the Kinshasa series, 168 (89.4%) of 188 parasitologically confirmed cases were positive by antigen ELISA. The controls, who included 165 blood donors and 40 patients with malaria, 2 with hydatidosis and 12 with leishmaniasis, were negative by antigen ELISA. Analysis of CSF results for 35 patients who had antigens in CSF revealed that 34 (97.1%) had elevated CSF white cell counts, 29 (82.9%) had elevated protein levels, and 23 (65.7%) had trypanosomes in their CSF. Moreover, analysis of results for 34 patients whose CSF had been shown to harbour trypanosomes by the double centrifugation technique showed that 24 (70.6%) had antigens in CSF, 28 (82.6%) had elevated protein levels, and 33 (97.1%) had elevated CSF white cell counts. Antigens were rapidly cleared from peripheral circulation following institution of treatment. Antigen clearance was accompanied by a rapid fall in CSF protein levels and white cell counts. These results demonstrate the potential of antigen ELISA, not only as a tool for diagnosis, but also for clinical staging and treatment follow-up of patients with T. b. gambiense sleeping sickness.

Animals↗

Long-term exposure of Trypanosoma brucei gambiense to pentamidine in vitro.

In order to study the sensitivity in vitro of Trypanosoma brucei gambiense to pentamidine, 5 x 10(4) parasites were exposed to 0, 0.1, 1.0, 2.0, 10, 100, 1000 and 10,000 micrograms/L of pentamidine isethionate for up to 10 d. The viability of parasites was determined each day by microscopy. Multiplication was retarded during continuous exposure to 2 micrograms/L. After 4 d no further multiplication took place, although the trypanosomes remained alive for another 3 d. The parasiticidal effect was more pronounced when higher concentrations were used; when exposed to 10 and 100 micrograms/L, all parasites were dead after 4 and 3 d, respectively. Despite exposure to 1000 micrograms/L, 74% of the parasites were still alive the next day. 10,000 micrograms/L killed all parasites within 24 h of exposure. Our results show that the time period of exposure to pentamidine plays a major role in determining the sensitivity in vitro of T. b. gambiense, and we suggest that prolonged exposure in vivo may be more important than attaining high but brief peak concentrations.

Animals↗

A comparison of parasitological methods for the diagnosis of gambian trypanosomiasis in an area of low endemicity in Côte d'Ivoire.

The card agglutination test for trypanosomiasis (CATT) was used to examine 8974 inhabitants in 14 village areas south-west of Daloa, Côte d'Ivoire; 114 (1.3%) were CATTT or +/-, and were further examined by one or more of 6 methods for the direct detection of trypanosomes: lymphatic gland puncture, stained thick blood film (TBF), haematocrit centrifugation technique (HCT), mini-anion exchange column (MAEC), quantitative buffy coat method (QBC), and kit for in vitro isolation of trypanosomes (KIVI). Trypanosomes were seen by at least one method in 16 (14.0%) of the CATT+ group. Blood from 356 of the 8860 CATT- group was inoculated into KIVI; trypanosomes grew from the blood of 1 person. Eleven of the 17 patients with detectable trypanosomes were screened by all 6 methods: 6 were HCT+; 7 were gland+; 10 were MAEC+; 10 were KIVI+; 11 were both TBF+ and QBC+. One CATT+ patient was KIVI+ but otherwise negative, although TBF was not done. The overall prevalence of trypanosomes was 0.2% rising to 0.8% in one village area. The results support previous evidence that a reappraisal of procedures is required in the customary system of surveillance for gambian sleeping sickness.

Agglutination Tests↗

Human immunodeficiency virus infection and human African trypanosomiasis: a case-control study in Côte d'Ivoire.

To assess the association between human immunodeficiency virus (HIV) infection and human African trypanosomiasis (HAT) in Côte d'Ivoire, West Africa, a cross-sectional case-control study was conducted on 301 HAT patients recruited in the main foci of the country. For each HAT patient, 3 controls, matched for sex, age and residence, were selected. Data relating to socio-demographic factors and potential risk factors for Trypanosoma brucei gambiense and HIV infections were obtained, and serum samples were collected for HIV-1 and HIV-2 tests. A positive test consisted of enzyme immunoassay reactive to HIV-1, HIV-2 or both and confirmed by a synthetic peptide test or Western blot. Data were analyzed using conditional logistic regression with EGRET software. No statistically significant difference was found between the prevalence of HIV infection in HAT patients and controls (4.3% and 3.5% respectively; crude odds ratio (OR) 1.28, 95% confidence interval (CI) 0.65-2.50). In multivariate analysis, allowance for 5 covariates did not change the association between the 2 infections (adjusted OR 1.27, 95% CI 0.64-2.52). Although this study had limited statistical power, no significant association was found between HIV infection and T.b. gambiense infection in rural Côte d'Ivoire. Studies are needed to determine whether HIV infection influences the clinical course of HAT, a question not addressed in the present study.

Adolescent↗

Human African trypanosomiasis (T.b. gambiense): a study of 16 fatal cases of sleeping sickness with some observations on acute reactive arsenical encephalopathy.

The principal clinical and pathological findings in 16 fatal cases of human African trypanosomiasis caused by T.b. Gambiense are described. The changes in the brain took the form of a non-specific lymphoplasmacytic meningo-encephalitis of varying intensity. Other features included morular cells, diffuse microglial hyperplasia, and large reactive astrocytes in the white matter. Carditis was identified in 10 cases. Acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 patients. Convulsions figured prominently in this type of encephalopathy in seven patients and were sufficiently severe to produce hypoxic brain damage. In three cases of acute reactive arsenical encephalopathy the structural changes in the brain were those of acute haemorrhagic leucoencephalopathy.

Acute Disease↗

Pharmacokinetic properties of the trypanocidal drug melarsoprol.

With a biological assay and atomic absorption spectrometry we determined the level of melarsoprol in the serum and cerebrospinal fluid of 19 patients treated with melarsoprol in Daloa, Ivory Coast. Most serum levels were between 2 and 4 micrograms/ml 24 h after administration, and were still > or = 0.1 microgram/ml after 120 h. Levels in the cerebrospinal fluid were between 0 and 0.1 microgram/ml. Elimination was biphasic, with a pronounced beta 1 phase. Mean terminal elimination half-life of melarsoprol was about 35 h, volume of distribution was about 100 l and total clearance was about 50 ml/min. The results of these first pharmacokinetic studies on melarsoprol were used to simulate possible alternative therapy schemes which might avoid some of the problems that arise with melarsoprol use.

Adult↗

[Risk factors for human African trypanosomiasis in the endemic foci of Ivory Coast].

A case-control study on risk factors of Trypanosoma brucei gambiense human african trypanosomiasis was carried out in 111 patients diagnosed in the three main foci of Ivory coast. Each case was age and sex matched with one seronegative control living in the same locality. Based upon previous epidemiological surveys conducted in similar areas, the potential risk factors were identified and assessed using a standard questionnaire. The study demonstrates that in the forest area of Ivory coast human trypanosomiasis in a behavioral disease affecting mainly coffee and cocoa farmers. The allogenous populations coming from sudano-sahelian savannah are more exposed to the disease than other ethnic groups. People sleeping at the farm (encampments) are more likely to become infected than those living at the village (ODDS-Ratio = 4.5). People fetching water in natural holes and pools have an increased risk (ODDS-Ratio = 3.6). Cases reported more often than controls that they are foodstuffs dealers from the farms to the villages (ODDS-Ratio = 13.0). These results are consistent with data from previous studies. We identified preventable risk factors, upon which interventions should be carried out to reduce the incidence of the disease. The possibility of using these findings to improve sleeping sickness control programme in the forest areas of Ivory Coast is discussed.

Case-Control Studies↗