Biomedical subjects

F Doua

Publications and source records attributed to F Doua.

At least 19 recordsLinked to original sources

PubMed2004

The pharmacokinetics of eflornithine (alpha-difluoromethylornithine) in patients with late-stage T.b. gambiense sleeping sickness.

OBJECTIVE: To investigate the plasma, cerebrospinal fluid (CSF) levels and pharmacokinetics of eflornithine (DFMO) in patients with late-stage T.b. gambiense sleeping sickness who were treated with an oral DFMO at 100 mg/kg or 125 mg/kg body weight every 6 h for 14 days. METHODS: Plasma and CSF concentrations of DFMO were measured during day 10 and day 15 in patients following oral DFMO at 100 mg/kg (group I: n=12) and 125 mg/kg (group II: n=13) body weight every 6 h for 14 days. Clinical and parasitological assessments were performed at 24 h after the last dose of DFMO and at 12 months. RESULTS: Patients in each group had a good initial response, but relapse was observed in six patients (three patients for each group) during 12 months follow-up. Plasma DFMO concentrations did not increase proportionally to doses when the dose increased from 100 mg/kg to 125 mg/kg body weight given every 6 h (60-70% of the expected increase). In most cases, concentration-time profiles of DFMO in each group were best fit using a two-compartment open model with first-order input, with absorption lag-time and first-order elimination. Average trough (C(ss-min)) and average (C(ss-ave)) plasma DFMO concentrations during steady state varied between 189-448 nmol/ml and 234-528 nmol/ml, following 100 mg/kg and 125 mg/kg dose group, respectively. C(max), t(max) and AUC(0- infinity ) values following the last dose were 296-691 nmol/l, 2-3 h, and 2911-6286 nmol h/ml, respectively. V(z)/F, CL/F and t(1/2z) values were 0.47-2.66 l/kg, 0.064-0.156 l/h/kg, and 3.0-16.3 h, respectively. CSF concentrations at steady state varied between 22.3 nmol/ml and 64.7 nmol/ml. Patients who had treatment failure tended to have lower plasma and CSF DFMO concentrations than those who had successful treatment. CONCLUSION: Oral DFMO at the dose of 125 mg/kg body weight given every 6 h for 14 days may not produce adequate therapeutic plasma and CSF levels for patients with late-stage T.b. gambiense sleeping sickness.

Adolescent↗

PubMed2003

Human African trypanosomiasis: quantitative and qualitative assessment of intrathecal immune response.

Quantitative and qualitative techniques for assessment of the intrathecal humoral immune response in human African trypanosomiasis were compared, and their diagnostic potential for detection of the meningo-encephalitic stage of the disease was evaluated. Total and trypanosome specific immunoglobulin G (IgG) and IgM intrathecal synthesis were studied in paired cerebrospinal fluid (CSF) and blood samples of 38 trypanosomiasis patients and in three controls using Reiber's formulae. The presence of CSF-specific oligoclonal IgG and of trypanosome-specific antibodies was determined using iso-electric focusing followed by immunoblotting and antigen-driven immunoblots. The intrathecal IgG fraction (16% positive) and oligoclonal IgG detection (24% positive) were insensitive for detection of an intrathecal humoral immune response. Trypanosome-specific IgG synthesis, reflected by the IgG antibody index (AI) (26% positive), was confirmed by the presence of oligoclonal specific IgG (47% positive), but the latter was more sensitive. Although the detection technique failed for oligoclonal IgM, the intrathecal IgM fraction (42% positive) and the IgM AI (32% positive) indicated that the meningo-encephalitic stage of the disease is characterized by a dominant intrathecal IgM response, which was higher than the IgG response. The highest combination of diagnostic sensitivity and specificity for the meningo-encephalitic stage of trypanosomiasis was observed for quantitative IgM determinations.

Albumins↗

PubMed2002

IgM quantification in the cerebrospinal fluid of sleeping sickness patients by a latex card agglutination test.

An increased IgM concentration in cerebrospinal fluid (CSF), occurring as a consequence of massive intrathecal IgM synthesis, is a marker of interest for diagnosis of the meningo-encephalitic stage in human African trypanosomiasis. However, in current practice, IgM in CSF is not determined because of the lack of a simple and robust test that is applicable in African rural regions where the disease prevails. We describe the development of a sensitive semiquantitative card agglutination test, LATEX/IgM, for IgM quantification in CSF. The test is simple and fast and the lyophilized reagent remains stable even at 45 degrees C. CSF end-titres obtained with LATEX/IgM parallel the IgM concentrations determined by nephelometry and enzyme-linked immunosorbent assay. Detection of intrathecal IgM synthesis is the most sensitive marker for CNS involvement in sleeping sickness. At a cut-off value of >or= 8, the sensitivity and specificity of LATEX/IgM for intrathecal IgM synthesis are 89.4 and 92.7%. As a consequence, patients with LATEX/IgM end-titres >or= 8 are likely to have intrathecal IgM synthesis, thus central nervous system involvement and therefore should be treated accordingly. Further studies should concentrate on the relationship between the LATEX/IgM end-titres, presence of intrathecal IgM synthesis and occurrence of treatment failures in patients treated with pentamidine.

Animals↗

PubMed2002

[Geographic distribution of trypanosomiasis treated in Ivory Coast from 1993 to 2000].

Human African Trypanosomosis (HAT, or sleeping sickness) caused by Trypanosoma brucei gambiense develops chronically in Côte d'Ivoire. From 1993 to 2000, a total of 1616 patients were taken in charge in the three treatment centres of the country, which means an average of 202 patients a year. The patients came from two main areas in the Centre West of the country in the Marahoué region: the districts of Sinfra, South of Bouaflé, and Bonon, West of Bouaflé. In the Centre West and in the South East of the country (Aboisso-Ayamé), patients are still struck by the disease, although these foci are less active. The remaining foci seem to be controlled, although no active survey has been carried out. The areas where the greatest number of patients were recorded are the ones where rental crops are located (cocoa and coffee mainly) and where rural activities tend to bring humans and tsetse flies in contact. In this study, are figured the number of treated patients, the endemic and risk areas. It will help to design control strategies and decision makers to know where priority control programs should be implemented.

Agriculture↗

PubMed2002

[Human African trypanosomiasis in Ivory Coast: biological characteristics after treatment. 812 cases treated in the Daloa focus (Ivory Coast)].

The treatment and post therapeutic follow up of patients diagnosed with HAT are important for HAT control. A longitudinal survey was implemented in the focus of Daloa (Côte d'Ivoire). A total of 812 patients infected with Trypanosoma brucei gambiense in meningoencephalitic stage and treated with melarsoprol were included, this study pointed out the biological characteristics of patients after treatment. The relapse occurs between 1 and 24 months after treatment. It is essentially neurological, and characterised by the presence in the CSF of antibodies, by the increase of cell count compared with value immediately after treatment, or by the presence of trypanosomes. The cure can be confirmed from 18 months after treatment, and is characterised by the absence of antibodies and trypanosomes in the CSF, by a normal cell count and a normal proteinorachy. Biological scares were recorded on some of the patients after 18 months of follow up, but no relapse occurred among them.

Animals↗

PubMed2000

Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial.

OBJECTIVE: A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective as the standard 14-day regimen in the treatment of late-stage Trypanosoma brucei gambiense trypanosomiasis. METHODS: A total of 321 patients (274 new cases, 47 relapsing cases) were randomized at four participating centres in Congo, Côte d'Ivoire, the Democratic Republic of the Congo, and Uganda to one of these treatment regimens and followed up for 2 years. RESULTS: Six patients died during treatment, one of whom was on the 7-day regimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countries. Among new cases in Uganda, the 2-year probability of cure was 73% on the 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Côte d'Ivoire, Congo, and the Democratic Republic of the Congo combined, the 2-year probability of cure was 97% on the 14-day course compared with 86.5% on the 7-day regimen (HR for treatment failure, 7-day vs 14-day: 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0.003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors associated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1; 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count > or = 100/mm3 (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI: 0.9-4.1). Being stuporous on admission was associated with a lower risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing age (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). DISCUSSION: The 7-day course of eflornithine is an effective treatment of relapsing cases of Gambian trypanosomiasis. For new cases, a 7-day course is inferior to the standard 14-day regimen and cannot be recommended.

Adolescent↗

PubMed1998

Assessment of central nervous system involvement in gambiense trypanosomiasis: value of the cerebro-spinal white cell count.

OBJECTIVE: To assess, in a clinical setting, the comparative values of conventional criteria used in the diagnosis of central nervous system (CNS) involvement in Trypanosoma brucei gambiense sleeping sickness: white cell count (WCC) in cerebrospinal fluid (CSF) > 5 x 10(6) cells/l; total protein concentration in CSF > 40 mg/100 ml); evidence of trypanosomes in CSF following double centrifugation (DC). METHOD: In vitro culture of CSF was used as the gold standard. RESULTS: The study showed that WCC is, by itself, as sensitive for the diagnosis of the CNS involvement as the usually recommended combination of three conventional criteria. The specificity of WCC is improved while the sensitivity is reduced when the cut-off point is set at a higher value (WCC > 10 X 10(6)/l). CONCLUSION: In poorly equipped laboratories, the diagnosis of CNS involvement in patients with confirmed systemic infection should be based only on the WCC. However, a pilot study is needed to assess the feasibility and reliability of the WCC handled by 'front line' personnel, for different cut-off values.

Animals↗

PubMed1998

Discrepancy in plasma melarsoprol concentrations between HPLC and bioassay methods in patients with T. gambiense sleeping sickness indicates that melarsoprol is metabolized.

OBJECTIVE: With the use of a specific high-performance liquid chromatography (HPLC) method and a bioassay which determines trypanocidal activity, concentrations of melarsoprol were assessed in plasma, urine and cerebrospinal fluid (CSF) from 8 patients with late-stage Trypanosoma gambiense sleeping sickness. The aim was to unravel to what extent the bioassay codetermines biologically active metabolites of melarsoprol. METHODS: Subjects were given one dose of melarsoprol i.v. per day for 4 days (1.2, 2.4, 3.0-3.6, 3.0-3.6 mg per kg b.w., respectively). Plasma samples were obtained before the first melarsoprol injection, immediately after and at 1 h, 24 h and 5 days after the 4th injection. Urine was collected before melarsoprol therapy and at 24 h after the 4th injection. CSF samples were taken once before treatment and at 24 h after the 4th injection. RESULTS: HPLC analyses showed that plasma concentrations immediately after the 4th injection varied from 2200 to 15,900 nmol/l; dropping to 0-1800 nmol/l at 1 h; and to undetectable levels at 24 h. In urine small amounts of melarsoprol were recovered. Melarsoprol could not be detected in CSF by HPLC. Immediately after injection, bioassay analyses showed plasma concentrations of the same magnitude as HPLC assays but at 1 h they were 4-65-fold higher than the levels assessed by HPLC. Even 24 h and 5 days after the 4th injection there was significant but decreasing activity. Urine levels were 40-260-fold higher than the measured HPLC concentrations, whereas there was low but detectable activity in CSF. CONCLUSION: Results indicate that melarsoprol is rapidly eliminated from plasma. The significant trypanocidal activity determined by bioassay and simultaneous low or undetectable levels of melarsoprol assayed by HPLC indicate that the compound is transformed into metabolites with parasiticidal activity.

Adolescent↗

PubMed1998

A multi-centre evaluation of the card indirect agglutination test for trypanosomiasis (TrypTect CIATT).

A version of the card indirect agglutination test for trypanosomiasis, the TrypTect CIATT, was evaluated for the diagnosis of Trypanosoma brucei gambiense and T. b. rhodesiense sleeping sickness. The results of this antigen-detection test indicated high relative sensitivity (99.3%) and specificity (99.4%), and also much higher prevalences of infection in the general population of endemic foci (27.9% for T. b. gambiense and 21.8% for T. b. rhodesiense) than detected by parasitological diagnosis (1.6% and 1.1%, respectively). TrypTect CIATT detected (and could therefore be used for the diagnosis of) non-patent infections. Among the suspected cases (i.e. those initially found to be parasite-negative but to be antigen-positive), trypanosomes were detected in 29 (4.2%) of those checked at a 3-month follow-up, and 17 more such suspects when they were followed up at 6-18 months. Moreover, a high proportion of blood samples from a random sample of the rest of the suspects tested positive for trypanosome-specific DNA by PCR (79.9% for T. b. gambiense and 13.9% for T. b. rhodesiense). ELISA also demonstrated the presence of anti-trypanosome antibodies in many of the suspects tested (63%, 38%, 24% and 66.9% of those in Cameroon, Côte d'Ivoire, Tanzania, and Malawi, respectively). A follow-up of 164 patients treated with melarsoprol revealed that, by 9 months post-treatment, 113 (69.0%) had no detectable trypanosome antigens in their peripheral blood. The test could therefore be used for evaluating chemotherapeutic cure, as well as for diagnosis.

Adult↗

PubMed1998

[Detecting sleeping sickness: comparative efficacy of mobile teams and community health workers].

The solution to the problem of human African trypanosomiasis (HAT) first of all requires improved case detection. Effective tests have been available for a number of years but the results of medical surveys are still mediocre, mainly because the populations are poorly mobilized. Those few mobile teams still visiting villages obtain very low presentation rates. In spite of major information campaigns among villagers, in Côte d'Ivoire the Institut Pierre Richet (IPR) and Trypanosomiasis Clinical Research Project (PRCT) teams examined only 42% (9311) of the 22,300 inhabitants of a disease focus during a conventional ten-day survey. In the same focus, community health workers specially trained in sleeping sickness and in the collection of blood samples on filter-paper examined 73% of the population (15,000 individuals) in less than two months. Implementation of a sleeping sickness control strategy is restricted to two types of intervention: either conventional mobile teams which are on hand, competent and rapidly operational but which fail to carry out exhaustive case detection, or integration of case detection into primary health care by entrusting surveillance to the community health workers. This approach requires a minimum of training but ensures that sentinels are permanently present in the village communities. By using the community health workers rather than mobile teams it should be possible to achieve comprehensive monitoring. In operational terms, the cost of surveillance per person is US$ 0.55 for the mobile teams as against US$ 0.10 for the community health workers. Integration of HAT case detection into primary health care is therefore an effective and economical solution, provided the community health workers are properly supervised and above all motivated.

Community Health Workers↗

PubMed1997

Endotoxin antibodies in African sleeping sickness.

Antibodies to the core region of endotoxin (endotoxin core antibodies, EndoCAb), which cross-react with endotoxin from a range of Gram-negative bacteria, are maintained in relative homeostasis in health, but undergo marked changes in a number of different diseases associated directly or indirectly with endotoxaemic or septicaemic states. The levels of EndoCAb IgG in the blood and cerebrospinal fluid (CSF) of 35 late-stage sleeping sickness patients and 9 control individuals were measured by ELISA. EndoCAb levels were significantly elevated in the patient blood (mean EndoCAb value 290 MU/ml cf. control 182 MU/ml, P < 0.001), and CSF (mean EndoCAb value 254 MU/ml cf. control 150 MU/ml, P < 0.001). EndoCAb IgG levels correlated with endotoxin levels in patient blood (r = 0.78, P < 0.001), but not in the CSF and were not reduced 6 weeks following chemotherapy, unlike the endotoxin levels. It is concluded that late-stage sleeping sickness is associated with chronic exposure to endotoxins from Gram-negative bacteria.

Antibodies, Bacterial↗

PubMed1997

Detection and characterization of autoantibodies directed against neurofilament proteins in human African trypanosomiasis.

In serum and in cerebrospinal fluid (CSF) from patients with human African trypanosomiasis (HAT) with central nervous system involvement, we detected autoantibodies directed to some proteins from these tissues. The characterization of antigenic proteins by Western blotting showed that the antibodies recognized the 200-kD and 160-kD proteins of neurofilament (NF). Serum anti-NF antibodies were more frequent in HAT patients than in control subjects (86% versus 24%; P < 10[-9]) and they belonged predominantly to the IgM class (anti-NF IgM = 86% versus anti-NF IgG = 4%; P < 10[-9]) in the patients with stage II (central nervous system involvement) HAT. The CSF antibodies to NF were IgM in 88% (22 of 25) of the cases and IgG in 32% (8 of 25) of the cases. Epitopes shared by NF and trypanosomes were detected by indirect immunofluorescence and this was confirmed by the disappearance of anti-NF reactivity after adsorption with trypanosome antigens (Trypanosoma brucei brucei or T. b. gambiense). Anti-NF antibodies were undetectable in the CSF from stage I HAT patients.

Animals↗

PubMed1997

[Blood levels of protein markers of inflammation and nutrition in the meningo-encephalitis phase of human African trypanosomiasis].

Two acute phase proteins; C-reactive protein and acid alpha 1-glycoprotein and three nutritional markers; prealbumin, retinol binding protein and transferrin have been evaluated in 8 patients suffering from trypanosomiasis in meningoencephalitic state and compared to those obtained from 15 normal control subjects. Findings show a markly decrease of nutritional markers without change of sera acute phase proteins. We concluded that in meningo-encephalitic state of human african trypanosomiasis, denutrition was a major biological or clinical feature in association with lymphoid cells stimulation as revealed by beta 2-M levels.

Acute-Phase Proteins↗

PubMed1997

In vivo evaluation of sixteen plant extracts on mice inoculated with Trypanosoma brucei gambiense.

After examination of the drugs used by traditional practitioners in Côte d'lvoire, nine formulas prescribed in the treatment of African human trypanosomiasis (AHT) were selected for investigation. These formulas made use of 40 plants, 16 of which were studied because of their properties, as described in the literature, and their frequent use by practitioners. The plant extracts were administered, after maceration or decoction, either orally or intraperitoneally to Swiss mice that had previously been inoculated with Trypanosoma brucei gambiense (Tbg), strain MHOM/Cl/81/Dal 083. The parasitaemia in each mouse was followed for three consecutive days and compared with that in control mice, which had been given either a saline solution (SS: negative control) or well-known drugs (melarsoprol, difluoromethylornithine, and pentamidine: positive control). Our investigations led to the following conclusions. (a) None of the plant extracts revealed trypanocidal or trypanostatic activity relative to SS controls (P > 0.05). In fact, the mice that received the extracts died on the third day after inoculation, with 0% survival and an average parasitaemia of 10.8 +/- 2 x 10(7) trypanosomes/ml. (b) The treated positive controls, relative to SS, showed 100% survival and no parasitaemia (P < 0.05). Melarsoprol appeared to be active when given orally at a dose of 3.6 mg/kg body weight twice a day for 3 days. This method of testing the sensitivity of trypanosomes to plant extracts is easy and inexpensive, and could be applied to other areas of research on tropical diseases.

Administration, Oral↗

PubMed1996

Endotoxins in the blood and cerebrospinal fluid of patients with African sleeping sickness.

Endotoxin levels were measured in the blood and cerebrospinal fluid (CSF) of control individuals and 2 groups of patients with African sleeping sickness. Endotoxin levels were markedly elevated in the blood (infected groups mean endotoxin values 40.2 pg/ml and 53.8 pg/ml, compared to control 11.6 pg/ml, P < 0.0001 for both increases) and CSF (infected groups mean endotoxin values 45.8 pg/ml and 50.1 pg/ml compared to control 6.3 pg/ml, P < 0.0001 for both increases) of the patients. The levels were reduced 6 weeks following different drug treatments in the 2 groups (blood levels to mean 33.8 pg/ml and 28.5 pg/ml; CSF levels to 37.4 pg/ml and 27.0 pg/ml). The blood endotoxin values correlated with the CSF values before treatment (r = 0.74 and 0.57 for the 2 groups; P < 0.0001 for both) and after treatment (r = 0.57 and 0.56 for the 2 groups; P < 0.0001 for both). It is concluded that raised endotoxin equilibrates in the blood and CSF compartments, and may contribute significantly to the pathology of sleeping sickness.

Adolescent↗

PubMed1996

Electroencephalographic and polygraphic features of 24-hour recordings in sleeping sickness and healthy African subjects.

Electroencephalographic (EEG) and polygraphic features were analysed in six healthy control subjects and eight patients suffering from sleeping sickness meningoencephalitis in order to determine possible functional relationships. One patient was disqualified because of intermittent metabolic disease. Twenty-four h polygraphic recordings-EEG, electrooculography (EOG), electromyography (EMG), nasal and buccal air flow, chest respiratory movements-were performed continuously both on paper and on cassette tapes. Tapes were played back on paper (paper speed: 15 mm/s). Traces were analyzed for normal and pathologic features, and transient activation phases and paroxysmal hypnopompic hypersynchrony events were counted. During wakefulness, slow theta and delta waves occurred in four patients, but alpha reactivity was present. During sleep, normal features were seen. However, transient activation phases were decreased in the patients. During slow-wave sleep, four patients presented predominantly monophasic frontal delta bursts along with paroxysmal hypnopompic hypersynchrony events. In conclusion, in sleeping sickness patients, although dampened, the waking process remains responsive and slows down only during the late stage of meningoencephalitis.

Adolescent↗

PubMed1996

Detection of Trypanosoma brucei spp. in human blood by a nonradioactive branched DNA-based technique.

We have developed a nonradioactive branched DNA (bDNA)-based assay for the diagnosis of the African trypanosomiases in simple buffy coat preparations of human blood. Two repetitive DNA sequences specific to the Trypanosoma brucei complex were chosen as targets of the bDNA assay, a technique which amplifies the signal from a target molecule rather than the target itself. Comparable sensitivities were observed with cloned target sequences, purified T. brucei DNA, procyclic trypanosomes, and bloodstream trypomastigotes. The results of bDNA analysis of human blood samples from Côte d'Ivoire (n = 50) showed excellent agreement with those of buffy coat microscopy. The bDNA technology offers certain advantages over alternative molecular biological techniques, including the simplicity of sample preparation and of the procedure itself, the stability of the reagents, the ability to process large numbers of samples simultaneously, and freedom from crosscontamination artifacts. We have successfully applied the bDNA technique to the detection of T. brucei in clinical samples from regions where T. brucei infection is endemic; to our knowledge, this is the first report of the molecular detection of T. brucei in human blood.

Animals↗

PubMed1996

Relationship of plasma growth hormone to slow-wave sleep in African sleeping sickness.

Human African trypanosomiasis (sleeping sickness) is a unique disease model of disrupted circadian rhythms in the sleep-wake cycle and cortisol and prolactin secretion. This study examined the temporal relationship between growth hormone (GH) secretion and the sleep-wake cycle in 8 infected African patients and 6 healthy indigenous African subjects. Twenty-four-hour sleep patterns were recorded by polysomnography and hourly blood samples analyzed for plasma GH. No relationships between the mean normalized plasma GH levels (Z scores) and the sleep stages (wakefulness, sleep stages 1 and 2 ('light' sleep), slow-wave sleep (stages 3 and 4, SWS), and rapid eye movement (REM) sleep) were found in the patients or healthy subjects. However, when the time of sampling of the plasma GH concentrations was lagged by 16 min with respect to the occurrence of the various sleep stages, significant correlations were found between plasma GH concentrations and SWS in both healthy subjects and patients. Thus, the association between SWS and GH secretion persisted even in the presence of disrupted circadian rhythms, further supporting the concept that sleep and the stimulation of GH secretion are outputs of a common mechanism.

Adolescent↗