Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.

BACKGROUND: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. METHODS: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. FINDINGS: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). INTERPRETATION: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. FUNDING: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

[Identification of yeasts from commercial attiéké in Abidjan (Côte d'Ivoire): Preliminary study]. / Identification des espèces de levures isolées de l'attiéké commercialisé sur les marchés à Abidjan (Côte d'Ivoire) : étude préliminaire.

OBJECTIVE: This study aims to identify yeasts from commercial attiéké. PATIENTS AND METHODS: This descriptive cross-sectional survey involving 103 samples of attiéké sold on the market from August to September 2017. It was conducted from the mycology laboratory of the Institut Pasteur of Côte d'Ivoire. The samples were seeded on YGC medium. The colonies of positive culture were counted and seeded again on chromogen medium. Identification of yeasts species was carried out by MALDI-TOF mass spectrometry (Vitek MS bioMérieux). RESULTS: As a whole, 63 samples were contaminated with fungi i.e. an overall prevalence of 61.1 %. Fifty-nine of yeasts were identified i.e. 57.2 %. Candida rugosa was most frequently isolated (62.7 %), followed by Ccandida albicans (8.5 %), Candida krusei (8.5 %) et Candida tropicalis (8.5 %). Geotrichum candidum represented 6.8 % isolated yeasts. The yeast average load is 10,124×102 CFU/g with high contamination of commercial attiéké in the commune of Abobo. CONCLUSION: The contamination of attiéké by yeasts is a reality. C. rugosa was most frequently isolated. It would be necessary to investigate the food chain to determine the source of contamination.

[Intestinal parasites in children in Biankouma, Ivory Coast (mountaineous western region): efficacy and safety of praziquantel and albendazole]. / Parasitoses intestinales infantiles à Biankouma, région des 18 Montagnes (ouest de la Côte d'Ivoire): étude de l'efficacité et de la tolérance du praziquantel et de l'albendazole.

Schistosomiasis and soil-transmitted helminthiasis are a global public health problem, especially among schoolchildren. The purpose of this study was to determine the overall and specific prevalences of intestinal helminth infection and to assess the clinical efficacy, tolerance, and safety of praziquantel and albendazole for treating it. A descriptive cross-sectional study based on random sampling with one degree of freedom was conducted from November 2006 to March 2007 in the primary schools of Biankouma, Côte d'Ivoire. Stool samples were collected from 386 children aged from 4 to 15 years and analyzed by direct examination, with both the simplified Ritchie and Kato techniques. Children infected by schistosomiasis and soil-transmitted helminthiasis eggs were treated with praziquantel (40 mg/kg in a single dose), albendazole (400 mg/kg in a single dose) or both, as deemed necessary. The prevalence rate of intestinal parasite infection was 55.2%, including overall 15.4% with more than one parasite: two in 14.2% and three in 1.2%. Infection was correlated with male gender and older age. The most frequent helminths were Schistosoma mansoni (35.5%) and Necator americanus (25.9%). The efficacy rate for praziquantel, defined as parasite-free stools, was 57.7% on day 14 and 80.9% on day 90. The efficacy rate for albendazole on day 7 was 96.1% for Ascaris lumbricoides, 93% for Necator americanus and 81.3% for Trichuris trichiura. Adverse effects were common (40.8%) but minor (abdominal pain, headache, and itching) within 2 to 4 hours after intake of praziquantel.

[A new focus of human paragonimosis discovered in Côte d'Ivoire (West Africa): the case of the Lauzoua Island]. / Un nouveau foyer de paragonimose humaine découvert en Côte d'Ivoire (Afrique de l'ouest): le cas de l'île de Lauzoua.

Fifteen cases of human paragonimosis were detected in Ivory Coast from 1974 to 1999. Since no further cases have been reported, an epidemiological survey was carried out in local health centers. The purpose of this paper is to described a new focus of paragonimosis discovered on Lauzoua Island. Clinical and parasitological examinations were performed on 17 patients presenting chronic cough, haemoptysis and/or epilepsy. Stools belonging to cats, dogs and pigs as well as river crustaceans were also examined to identify parasite eggs and metacercariae respectively. Paragonimus eggs were found in stools and/or sputum of five patients. Measurements of these eggs after fixation in formalin allowed division into three groups. Stools from cats, dogs and pigs were negative. Small Paragonimus metacercariae (mean: 277 to 323 microm) were found in three Callinectes marginatus crabs (out of 15 caught near the island). No metacercariae were found in local prawns. The presence of these three Paragonimus egg groups as well as of infected crabs near the island will require further study to identify the species and determine the prevalence of each in human infection.

First findings on the seroepidemiology of human paragonimosis at the anti-tuberculosis centre of Divo, Repubuc of Ivory Coast (West Africa).

An epidemiological study was carried out in 2004-2005 at the anti-tuberculosis centre of Divo (Ivory Coast) to collect sera from patients who consulted for tuberculosis suspicion and to estimate the seroprevalence of human paragonimosis in the context of a systematic screening. No Paragonimus egg was found in the stools and/or sputa of the 167 persons investigated. In contrast, 41 sera were ascertained with antibodies against Paragonimus africanus using ELISA testing. As the optical density (OD) values related to seropositive findings were found under 0.6 (the minimal OD to detect an active paragonimosis), the above antibody titres might originate from patients in chronic or in convalescent stages, or might result of cross reactions with trematodes. Concomitantly, dissection of local crabs (Callinectes marginatus) demonstrated the presence of Paragonimus metacercariae in six out of 34 examined. The parasite burdens in crabs ranged from two to 35 cysts with a mean diameter of 302 microm. In Ivory Coast, the locality of Divo must be considered an at-risk zone in reason of the presence of anti-Paragonimus antibodies in several human sera and the presence of infected crabs at the local market.

[Persistence of a paragonimosis focus in the department of Lakota, Côte d'Ivoire (West Africa)]. / Persistance d'un foyer de paragonimose dans le département de Lakota, Côte d'Ivoire (Afrique de l'Ouest).

A field survey was carried out from March to August 2006 in three villages around the town of Lakota (Côte d'Ivoire) to verify the presence of paragonimosis in local people, wild vertebrates, and crabs. Out of the 92 patients who were recruited because of their chronic cough, haemoptysis and/or epilepsy, 3 had Paragonimus eggs in their stools and/or sputa. Examination of stools belonging to 24 wild mammals and a reptile revealed the presence of eggs in three civets (Viverra civetta) and a mongoose (Crossarchus obscurus). Six local crabs (out of the 30 Liberonautes latidactylus dissected) harboured Paragonimus metacercariae having low diameters (299 to 315 pm). The presence of several paragonimid species (at least 2) in the district of Lakota was hypothesized. However, the existence of quantitative variations in metacercarial diameters for the same species of Paragonimus cannot be excluded.

[Epidemiological observations on the first case of human paragonimiasis and potential intermediate hosts of Paragonimus sp. in Benin]. / Observations épidémiologiques sur le premier cas de paragonimose humaine et les hôtes intermédiaires potentiels de Paragonimus sp. au Bénin.

Parasitological investigations were carried out for four months in 1998 in two Beninese centres of pneumo-phtisiology (Akpakpa, at Cotonou, and Akron, at Porto-Novo) to detect the patients harbouring eggs of Paragonimus sp. amongst the persons consulting for tuberculosis and showing a broncho-pneumopathy without mycobacteria. Eggs of Paragonimus sp. were detected in the sputum of a single patient out of 369 persons examined (prevalence, 0.2%). This patient had eaten crabs in the months preceding the date of diagnosis. A treatment using praziquantel has improved clinical symptomatology and biological signs found in this patient. These studies have been completed by visiting markets located in the coastal plain of Benin to identify the crabs that were sold and to find metacercariae of Paragonimus sp. Negative results were obtained when 126 Cardisoma armatum ("hole crab") were dissected. In contrast, the dissection of 176 Callinectes marginatus ("swimming crab") was successful, with 5% of crabs harbouring metacercariae of probably Paragonimus sp. Further studies are necessary to confirm these first results and to determine the global prevalence of Paragonimus infection in these definitive and intermediary hosts.