Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Communities’ Perception, Knowledge, and Practices Related to Human African Trypanosomiasis in the Democratic Republic of Congo

Background: The number of human African trypanosomiasis (HAT) cases in the Democratic Republic of Congo (DRC) has significantly reduced, thanks to more effective drugs and screening tools and regular mass screening. However, this potentially jeopardizes HAT control activities, especially community engagement. Methods: We used an ecological model framework to understand how various factors shape communities’ knowledge, perceptions, and behavior in this low endemicity context. Community members, frontline health providers, and policymakers were consulted using an ethnographic approach. Results: Communities in endemic areas are knowledgeable about causes, symptoms, and treatment of HAT, but this was more limited among young people. Few are aware of new HAT treatment or screening techniques. Participation in mass screening has declined due to many factors including fear and a lack of urgency, given the low numbers of cases. Delays in seeking medical care are due to confusion of HAT symptoms with those of other diseases and belief that HAT is caused by witchcraft. Conclusions: Community members see their role more in terms of vector control than participation in screening, referral, or accepting treatment. We propose recommendations for achieving sustainable community engagement, including development of an information and communication strategy and empowerment of communities to take greater ownership of HAT control activities

Les avortements clandestins au Centre Hospitalier Universitaire de Libreville de 2014 à 2018 : à propos de 212 cas

Objectif : Cette étude avait pour but d’étudier les aspects épidémiologiques cliniques et thérapeutiques des avortements clandestins dans le service de gynécologie interne du Centre Hospitalier Universitaire de Libreville de 2014 en 2018. Patients et méthodes : Il s’est agi d’une étude rétrospective, descriptive qui s’est déroulée du 1er janvier au 31 décembre 2018. Elle a porté sur toutes les patientes ayant pratiquées un avortement clandestin avec un âge gestationnel inférieur ou supérieur à 12 semaines aménorrhée, mariées ou célibataires, admises et/ou prise en charge dans le service de gynécologique interne du CHUL, dans la période de l’étude quelle que soit leur provenance. L’approche de collecte était une enquête par dépouillement de dossiers médicaux assortie à une étude des registres de compte rendu d’hospitalisation. Résultats : La fréquence moyenne annuelle des avortements provoqués était de 50±3,1 avortements pour 1000 accouchements. Cette fréquence a été multipliée par 5 en 2014 et 2018. L’âge moyen était de 27,3± 6,6 ans avec des extrêmes de 14 et 50ans. La majorité, soit 62,3% était du niveau secondaire, 79,9% était célibataires. L’âge gestationnel était connu pour 60,4% et inférieur à 12 semaines d’aménorrhée dans 46,7% des cas. Deux ethnies étaient majoritairement représentées : les fangs 32,1% et les punus 25,5%. Le lieu de l’avortement était principalement le domicile familial pour 72,6% des patientes. La méthode abortive utilisée était principalement le comprimé de misoprostol à 58,0%. Le motif de l’avortement était à 52,8% une grossesse non désirée plus ou moins associée à 22,6% à un manque de moyens financiers. Sur le plan clinique, le diagnostic retenu était principalement l’avortement compliqué d’une hémorragie (55,6%). La prise en charge comprenait : le  remplissage vasculaire (59,0%), l’AMIU (50,9%), l’antibiothérapie (88,6%) dominé par le métronidazole à 53,3%, la transfusion (60,8%), le fer et les acides foliques (35,4%), utérotonique (34,0%). La complication majeure était l’anémie (71,7%). L’évolution était favorable pour 92,5% dont 75% (soit 16/212) sont décédés en cours d’hospitalisation. Conclusion : L’avortement clandestin demeure un problème de santé publique dans notre pays, de par sa fréquence croissante, et ses omplications à type d’hémorragie pouvant engager le pronostic vital. La technique d’Aspiration Manuelle Intra utérine (AMIU) a encore montré son efficacité dans la prise en charge des complications de cette pratique avant l’âge gestationnel de 12 semaines d’aménorrhée. Sensibiliser davantage les populations sur les méthodes contraceptives et élargir sur le plan juridique l’accès à l’avortement médicalisé au premier trimestre de grossesse, pourraient amoindrir l’incidence et les complications de ces avortements dans notre region. Mots clés : Epidémiologie, clinique, thérapeutique, avortement clandestin, Libreville English Abstarct: Clandestine abortions at the Libreville University Hospital Center from 2014 to 2018: About 212 cases Objective: The aim of this study was to investigate the clinical and therapeutic epidemiological aspects of clandestine abortions in the internal gynecology department of the University Hospital of Libreville from 2014 to 2018. Patients and methods: This was a retrospective, descriptive study that took place from January 1 to December 31, 2018. It focused on all patients who had performed a clandestine abortion with a gestational age of less than or greater than 12 weeks of amenorrhea, married or single, admitted and/or managed in the internal gynecological service of the CHUL, in the period of the study regardless of their origin. The collection approach was a medical record survey combined with a study of hospitalization records. Results: The average annual frequency of induced abortions was 50±3.1 abortions per 1000 deliveries. This frequency increased 5-fold in 2014 and 2018. The average age was 27.3± 6.6 years extreme 14 and 50 years. The majority, 62.3% were of secondary school level, 79.9% were single. Gestational age was known for 60.4% and less than 12 weeks of amenorrhea in 46.7% of cases. Two ethnic groups were predominantly represented: the Fangs (32.1%) and the Punus (25.5%). The place of abortion was mainly the family home for 72.6% of patients. The abortion method used was mainly misoprostol tablets (58.0%). The reason for the abortion was an unwanted pregnancy in 52.8% of cases, more or less associated with a lack of financial means in 22.6%. Clinically, the diagnosis was mainly abortion complicated by hemorrhage (55.6%). Management included: vascular filling (59.0%), MVA (50.9%), antibiotic therapy (88.6%) dominated by metronidazole (53.3%), transfusion (60.8%), iron and folic acids (35.4%), uterotonic (34.0%). The major complication was anemia (71.7%). The evolution was favorable for 92.5% of which 75% (16/212) died during hospitalization. Conclusion: Clandestine abortion remains a public health problem in our country, due to its increasing frequency, and its complications such as hemorrhage that can be life threatening. The IMIU technique has again shown its effectiveness in the management of complications of this practice before the gestational age of 12 weeks of amenorrhea. Increased awareness of contraceptive methods and legal access to medical abortion in the first trimester of pregnancy could reduce the incidence and complications of these abortions in our religion. Keywords: Epidemiology, clinical, therapeutic, clandestine abortion, Libreville

Efficacy and safety of pafuramidine versus pentamidine maleate for treatment of first stage sleeping sickness in a randomized, comparator-controlled, international phase 3 clinical trial

Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine.; This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.; The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity

Treatment-emergent adverse events experienced by ≥5% of patients in either treatment group (treatment period).

<p>Treatment-emergent adverse events experienced by ≥5% of patients in either treatment group (treatment period).</p

Combined rate of cure and probable cure at 12 months.

<p>Combined rate of cure and probable cure at 12 months.</p

Clinical response definitions.

<p>Clinical response definitions.</p

Pafuramidine (DB289) Phase 3 study CONSORT flowchart.

<p>Pafuramidine (DB289) Phase 3 study CONSORT flowchart.</p

Secondary efficacy variables at months 3, 6, 12, 18, and 24 (per-protocol dataset).

<p>Secondary efficacy variables at months 3, 6, 12, 18, and 24 (per-protocol dataset).</p

Combined rate of cure and probable cure at 24 months.

<p>Combined rate of cure and probable cure at 24 months.</p