[Animal reservoir hosts of Trypanosoma brucei gambiense in Zaire: trypanosome infections in two foci in Bas-Zaire]. / Le réservoir animal de Trypanosoma brucei gambiense au Zaire: infections trypanosomiennes dans deux foyers du Bas-Zaire.

The prevalence of Trypanosoma spp. infections in domestic animals was estimated in a forest (Boma) and a savanna (Kimpese) sleeping focus in Bas-Zaire. The miniature anion-exchange centrifugation technique was used to determine the infection rates with T. congolense, T. vivax and T. brucei spp. in 505 animals. T. congolense predominated in both foci with the highest prevalence in pigs (76.2%), followed by sheep (31.3%), dogs (30.6%) and goats (7.4%). T. vivax was seen only on two occasions. In the forest zone, T. brucei spp. infections were frequent (pigs 16.5%, sheep 6.2%, dogs 3.4%, goats 1.1%) in contrast to the savanna area where only one T. brucei spp. infection was diagnosed. Twenty five primary isolations of T. brucei were done using different isolation and stabilization approaches. Isolates and stocks await behavioural, biochemical and molecular biological identification to discriminate T. b. brucei and T. b. gambiense of domestic animal origin.

[Clinical neurological signs of human African trypanosomiasis at the meningoencephalitis stage (apropos of 23 cases)]. / Signes cliniques neurologiques de la trypanosomiase humaine africaine au stade méningo encéphalitique (à propos de 23 cas).

Twenty-three patients with trypanosomiasis in the meningo-encephalitic period have been examined neurologically. Main neurological symptoms are evocative of the affection and consist in frontal syndrome, often shown by a cheiro-chin reflex, the most frequent objective neurological sign, extrapyramidal injury, neuro-endocrine dysfunction, vestibular, cerebellar, pyramidal and meningitis syndromes. Cerebro-spinal alterations are not steadfast.

[Trypanosomiasis at the Neuropsychopathologic Center of Kinshasa University]. / La trypanosomiase au centre neuropsychopathologique de l'Université de Kinshasa.

The recent building of a Neuropsychopathologic Center at the Kinshasa University now allows to carry out clinical, electroencephalographic studies on human african trypanosomiasis and soon neuropsychopathologic ones. These studies are reported here.

[Treatment of human trypanosomiasis caused by Trypanosoma brucei gambiense using alpha-difluoromethylornithine. Results in 7 patients]. / Traitement de la trypanosomiase humaine à Trypanosoma brucei gambiense par l'alpha-difluorométhylornithine. Résultats chez 7 patients.

Alpha-difluoromethylornithine (DFMO, eflornithine) is a specific irreversible inhibitor of ornithine decarboxylase, shown to be curative in various Trypanosoma species infections of animals. In the present open study, the efficiency of DFMO was assessed in 7 patients (4 Africans, 3 Europeans) with Trypanosoma brucei gambiense (Tbg) infection, 4 in the advanced stage and 3 in the early phase of the disease. Treatment with DFMO at initial dosages ranging 300-500 mg/kg/day administered IV (except 1 case) for 10-15 days, followed by 200-300 mg/kg/day per os for 28-69 days was associated with clearing of trypanosomes from blood within 1-4 days, a trend towards normalisation or full normalisation of all altered biological values characterizing the disease and disappearance of clinical symptoms. Side effects of DFMO, including loose stools (5 cases), anemia (3 cases) and decreased hearing (1 case), were mild and transient requiring no treatment or interruption of the drug, except in one case. Pharmacokinetic studies carried out in 4 patients, demonstrate penetration of the drug into CNS. In 6 cases, no evidence of relapse was found at 24 months posttreatment follow-up indicating that DFMO can be curative in early and late-stage of Tbg sleeping sickness. In 1 case, no relapse could be detected after a follow-up of 6 months. Further studies are needed to confirm our encouraging results and to determine the optimal regimens of DFMO for the cure of the early and late-stage of sleeping sickness.

[Arsenical resistance and difluoromethylornithine in the treatment of human African trypanosomiasis]. / Arsénorésistance et difluorométhylornithine dans le traitement de la trypanosomiase humaine africaine.

Human African trypanosomiasis (HAT) in Zaïre is a medical problem of first importance, particularly in endemic areas where sleeping sickness threatens about 10 millions of human beings almost the third of the whole population. Used since about forty years as the main trypanocidal drug, melarsoprol is accompanied with a more and more important rate of failures (10%) during the last ten years. 86 patients from whom 51 were refractory with melarsoprol have been treated with difluoromethylornithine (DFMO) since May 1984. Results which have been obtained seem to be encouraging because desperate cases are considered cured after 2 years of set-back. Side effects (disorders of intestinal function, anaemia, drug administration over a long period of time) may be considered as minor.

Difluoromethylornithine, an effective new treatment of Gambian trypanosomiasis. Results in five patients.

Recent studies have shown DL-alpha-difluoromethylornithine (eflornithine), an inhibitor of polyamine biosynthesis, to be curative in various Trypanosoma species infections of laboratory animals. Five patients are described with Gambian trypanosomiasis treated in Belgium with difluoromethylornithine, using various intravenous and oral dosage schedules. Three patients had late-stage and two had early-stage disease. Difluoromethylornithine treatment was associated with clearing of parasites from blood within one to four days, a trend towards normalization of all altered biologic values associated with the disease, and marked amelioration of clinical symptoms. Side effects of difluoromethylornithine, including loose stools in three patients and both anemia, and a decrease in auditory acuity in one patient, were mild, transient, and never required interruption of drug treatment. The presence of difluoromethylornithine in cerebrospinal fluid, determined in three patients, demonstrated that difluoromethylornithine penetrates into the central nervous system. In three patients, follow-up of at least 24 months after treatment demonstrated a continued healthy state without evidence of relapse. These promising, albeit preliminary, results of difluoromethylornithine therapy, even in patients with central nervous system involvement, indicate that extended clinical trials are warranted to determine the optimal dosage regimen in patients with early- and late-stage disease.

Expression of the B cell repertoire and autoantibodies in human African trypanosomiasis.

The relative importance of polyclonal B cell activation has been studied in relation to the development of autoantibodies in human African trypanosomiasis. In 34 patients investigated before specific treatment a broad expression of the B cell repertoire was observed including the production of anti-hapten (FITC, Penicillin, Phosphorylcholin) antibodies, of high levels of antibodies against some heterologous protein antigens (ovalbumin and tetanus toxoid) and of autoantibodies. Anti-ssDNA antibodies were detected in 84% of the patients and anti-IgG rheumatoid factors in 88%. Anti-striated muscle and anti-smooth muscle antibodies were also observed in 57 and 63% of the patients. Correlation analysis indicated that the formation of anti-DNA antibodies is associated with polyclonal B cell activation but probably depends on an additional B cell stimulation by released DNA or cross-reacting antigens. Anti-immunoglobulin antibodies are closely correlated with polyclonal B cell activation and their production is likely to reflect the high frequency of anti-IgG B cell precursors in the normal human B cell repertoire. The significance of these observations in relation to the pathological expression of trypanosomiasis should be particularly considered in the generation of immune complexes either in circulating blood or locally at the sites of parasite destruction.

Immune complexes in serum and in cerebrospinal fluid in African trypanosomiasis. Correlation with polyclonal B cell activation and with intracerebral immunoglobulin synthesis.

The possible occurrence of immune complexes (IC) in serum and in cerebrospinal fluid (CSF) has been studied in 36 patients with African trypanosomiasis (Trypanosoma brucei gambiense). In serum, very high levels of IC were detectable by the (125)I-C1q-binding and by the conglutinin-binding assays with positive results in 94 and 87%, respectively, of untreated patients. Circulating IC were found in both early and late stages of the disease, without significant quantitative differences; their size was 15-25S. There was a significant negative correlation between C3 values and C1qBA. Our studies suggest that circulating IC occurring during trypanosomiasis may be the expression of a polyclonal B cell activation. Indeed, there was a significant correlation (P < 0.001) between the levels of circulating IC and either the levels of IgM (mean value 12.5+/-7.2 mg/ml) or with the levels of rheumatoid factor-like antiimmunoglobulin antibodies that were detected by solid phase radioimmunoassay in 74% of the patients.IC were detected in 31 of 35 CSF samples, with a marked elevation in patients with definite involvement of the central nervous system as compared with earlier stages of sleeping sickness. The occurrence of IC in CSF was not related to an impairment of the blood-brain barrier as shown by analysis of CSF/serum albumin ratios. The level of IC in CSF did not correlate with the serum level and, therefore, circulating IC do not appear to cross efficiently an unimpaired blood-brain barrier. The analysis of IgG, IgM, and albumin concentrations in serum and CSF demonstrates a marked intracerebral immunoglobulin synthesis in patients with manifestations of meningoencephalitis. There was a correlation between CSF-C1q binding assay and this local IgG synthesis. These data are consistent with a local formation of IC in CSF in patients with active meningoencephalitis. The results obtained in eight patients followed during therapy suggest that the presence of IC in CSF may be an indicator of a continuing central nervous system disease and that the quantitation of CSF-IC may be useful for monitoring patient care.