Outbreak of facio-troncular dystonia in central Africa due to diazepam replaced by haloperidol in oral medications

Abstract

During week 52, 2014, in the north-east of the Democratic Republic of Congo, an African area included in the “Meningitis belt of Africa” and in which malaria is endemic, patients with suspected but atypical meningitis were reported. In January 2015, Médecins sans Frontières (MSF) Geneva, was approached by the Ministry of Health to support the outbreak. At the scene, data were collected on individual chart file records. Thereafter, at MoH and MSF case-management sites, information for each patient were recorded in a standardized Excel line-list. Patients’ demographic characteristics, clinical features, and discharge were recorded. At per request of the attending physician, cerebrospinal fluid was analysed for evidence of meningitis and blood for malaria. Toxicological analysis included liquid chromatography–Mass spectrometry and high performance liquid chromatography–UV spectrometry on urine specimens. Initial examination suggested that an illness other than bacterial meningitis was the cause of patients’complaints. Thereafter non-tonico-clonic seizures were considered. The MSF referent toxicologist was consulted. The definitive diagnosis made on pictures and videos. From January to August 2015, 1021 hospitalisations were recorded in 925 patients. Looking for the source of haloperidol showed that tablets sold as ‘diazepam’ and consumed by symptomatic patients contained haloperidol as the sole active pharmaceutical ingredient, suggesting that this large outbreak was due to haloperidol toxicity from falsified diazepam. However, the cause of the error is presently under investigation. This outbreak emphasizes the need to consider toxicity resulting from error in medicines when facing collective atypical signs and symptoms. To address such outbreaks, an international multidisciplinary collaboration, including clinical toxicologists, working in collaboration with medicine regulatory authorities is mandatory to address the major challenge of poor-quality drugs in developing countries. The mechanism and the cause of error in dosing are presently under investigation.