Clinical Features and Mortality Associated with Severe Malaria in Adults in Southern Mauritania

Abstract

Severe malaria in adults is not well studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (P < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, i.e. parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

Physiologically based pharmacokinetic modeling for dose optimization of quinine–phenobarbital coadministration in patients with cerebral malaria

“…The limitations of the study include the exclusion of the contribution of P‐glycoprotein transporter on quinine disposition (due to lack of information on in vitro studies) as well as the inhibitory effect of 3‐hydroxyquinine metabolite on CYP3A4 activity. Nevertheless, the significant impacts of these two factors on quinine disposition are unlikely 16 . Because of the limited information on phenobarbital i.v.…”

“…Nevertheless, the significant impacts of these two factors on quinine disposition are unlikely. 16 Because of the limited information on phenobarbital i.v. infusion in patients, one publication in healthy volunteers was used for phenobarbital model validation.…”

“…This is of concern as approximately 17.3% of adult patients with malaria had severe malaria, where 70.7% of the patients developed convulsions and the overall mortality rate was up to 14% of severe malaria cases. 16 Physiologically based pharmacokinetic (PBPK) modeling and simulation are accepted by various regulatory authorities as a promising tool to support dose optimization in the clinical phase of drug development, particularly for the investigation of drug-drug interactions (DDIs) and non-DDIs. 17 The present study aimed to apply PBPK modeling and simulation for the optimization of quinine and phenobarbital coadministration in adult patients with cerebral malaria with concurrent seizures.…”

“…Also, the optimal dose(s) of quinine when coadministered with phenobarbital has never been reported in this group of patients. This is of concern as approximately 17.3% of adult patients with malaria had severe malaria, where 70.7% of the patients developed convulsions and the overall mortality rate was up to 14% of severe malaria cases 16 …”

Investigating the epidemiological factors responsible for malaria transmission dynamics

“…In line with this, several malaria control efforts have focused on dissecting the characteristics of patients presenting with mild and severe malaria cases [15,16]. The specific characteristics of interest were often age, gender and travel history of the patients [16,17].…”