Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness.

In 2000, we reported that a new short treatment schedule of melarsoprol was not worse than the longer and demanding standard treatment for late-stage human African trypanosomiasis. This alternative schedule was assessed in an open, randomised clinical equivalence trial of 500 patients in Angola. 24 h after treatment, all patients were parasite free. Of 442 patients, 12 (3%) had relapsed after 1 year, of whom seven (3%) had had standard treatment and five (2%) the alternative treatment. After 2 years, 23 (5%) relapsing patients were reported, 11 (5%) in the standard treatment group and 12 (6%) in the new group. The results at the 2-year follow-up support and strengthen our previous findings.

[Clinical management of patients and deceased during the Ebola outbreak from October to December 2003 in Republic of Congo]. / Prise en charge des malades et des défunts lors de l'epidémie de fièvre hémorragique due au virus Ebola d'octobre a décembre 2003 au Congo.

Outbreaks of Ebola virus hemorrhagic fever (EVHF) have been reported since 2001 in the Cuvette Ouest department, a forested area located in the Western North of Congo. At the end of October 2003 a new alarm came from this department which was quickly confirmed as being an epidemic of EVHF. The outbreak response was organized by the ministry of health with the assistance of an international team under the aegis of WHO. The case management of suspect cases was done in an isolation ward set up at the hospital; when patients refused to go to the ward for care they were isolated in their house according to a protocol "transmission risks reduction at home". Safe burials were performed by specialized teams which respected the major aspects of the funeral to allow the process of mourning of the families. An active surveillance system was set up in order to organize the detection of new cases and the follow-up of their contacts. A case definition was adopted. From October 11 to December 2, 2003, 35 cases including 29 deaths were reported, 16 cases were laboratory confirmed. The first four cases had been exposed to monkey meat (Cercopithecus nictitans). The epidemic spread was due to family transmission. The population interpretation of the disease, in particular questions around wizards and evil-minded persons, is a factor which must be taken into account by the medical teams during communication meetings for behavioral change of the populations. The case management of patient in isolation wards to prevent the transmission of the virus in the community remains the most effective means to dam up Ebola virus hemorrhagic fever outbreaks. The good perception by the community of the safe funerary procedures is an important aspect in the establishment of confidence relations with the local population.

Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis.

Encephalopathies are the most feared complications of sleeping sickness treatment with melarsoprol. To investigate the existence of risk factors, the incidence of encephalopathic syndromes and the relationship between the development of different types of encephalopathies and the clinical outcome was studied in a clinical trial with 588 patients under treatment with melarsoprol. The 38 encephalopathy cases were classified into three types according to the leading clinical picture: coma type, convulsion type and psychotic reactions. Nine patients were attributed to the convulsion type, defined as a transient event of short duration with convulsions followed by a post-ictal phase, without signs of a generalized disease. None of these patients died from the reaction. Febrile reactions in the 48 h preceding the reaction were generally not observed in this group. Twenty-five patients were attributed to the coma type, which is a progredient coma lasting several days. Those patients often had signs of a generalized disease such as fever (84%), headache (72%) or bullous skin (8%) reactions. The risk of mortality was high in this group (52%). About 14/16 patients with encephalopathic syndrome of the coma type were infected with malaria. Patients with psychotic reactions or abnormal psychiatric behaviour (3/38) and one patient who died after alcohol intake were excluded from the analysis. The overall rate of encephalopathic syndromes in the cases analysed (n=34) was 5.8%, of which 38.2% died. We did not find any parameters of predictive value for the risk of developing an encephalopathic syndrome based on the symptoms and signs before treatment initiation. The appearance during treatment of febrile reactions (RR 11.5), headache (RR 2.5), bullous eruptions (RR 4.5) and systolic hypotension (RR 2.6) were associated with an increased risk for the occurrence of encephalopathic syndromes especially of the coma type.

Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial.

BACKGROUND: African trypanosomiasis is a fatal disease caused by protozoan parasites of the species Trypanosoma brucei. The disease has reached epidemic dimensions in various countries of central Africa. Treatment of the second stage is long and complicated, and is hampered by severe adverse reactions to the first-line drug, melarsoprol. Despite these problems, melarsoprol is likely to remain the drug of choice for the next decade. We therefore did a randomised trial comparing the standard treatment schedule with a new, concise regimen. METHODS: The safety and efficacy of the new schedule were assessed in patients presenting to a hospital in Kwanza Norte, Angola with sleeping sickness. The control group followed the 26-day standard Angolan schedule of three series of four daily injections of melarsoprol at doses increasing from 1.2 to 3.6 mg/kg within each series, with a 7-day interval between series. The new treatment schedule comprised 10 daily injections of 2.2 mg/kg. Primary outcomes assessed were elimination of parasites, deaths attributed to treatment, and rate of encephalopathy. Analysis was by intention to treat. FINDINGS: Of 767 patients with second-stage disease, 500 were enrolled: 250 were assigned the standard schedule, and 250 the new schedule. 40 patients on the standard schedule and 47 on the new schedule had adverse events which resulted in treatment disruption or withdrawal. 50 patients on the standard regimen deviated or withdrew from treatment, compared with two on the new regimen. Parasitological cure 24 h after treatment was 100% in both groups; there were six deaths (all due to encephalopathy) 30 days after treatment in each group. The number of patients with encephalopathic syndromes was also the same in each group (14). Skin reactions were more common with the new treatment, but all could be resolved by additional medication or withdrawal of treatment. INTERPRETATION: Considering the economic and practical advantages of the new 10-day schedule over the standard 26-day treatment schedule, and the similarity of treatment outcome, the new schedule is a useful alternative to the present standard, especially in epidemic situations and in locations with limited resources.