In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes.

BACKGROUND: Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure. METHODS: Isolates were collected from patients attending health centres in Abidjan with uncomplicated P. falciparum malaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay. RESULTS: 134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism. CONCLUSION: This study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.

Accuracy of a rapid diagnosis test, microscopy and loop-mediated isothermal amplification in the detection of asymptomatic Plasmodium infections in Korhogo, Northern Côte d'Ivoire.

BACKGROUND: Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d'Ivoire, using nested polymerase chain reaction (nPCR) as reference. METHODS: A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference. RESULTS: The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8-5.3), 5.2% (95% CI 3.9-6.6) and 18.8% (95% CI 16.4-21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1-29.4) and 100% for RDT, 20.0% (95% CI 7.8-32) and 100% for microscopy, and 93.3% (95% CI 85.7-100) and 95.4% (95% CI 92.2-100) for LAMP. CONCLUSION: In Northern Côte d'Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections.

Prevalence and Risk Factors for Schistosomiasis among Schoolchildren in two Settings of Côte d'Ivoire.

Schistosomiasis is a parasitic disease affecting more than 250 million people, primarily in sub-Saharan Africa. In Côte d'Ivoire both Schistosoma haematobium (causing urogenital schistosomiasis) and Schistosoma mansoni (causing intestinal schistosomiasis) co-exist. This study aimed to determine the prevalence of S. haematobium and S. mansoni and to identify risk factors among schoolchildren in the western and southern parts of Côte d'Ivoire. From January to April 2018, a cross-sectional study was carried out including 1187 schoolchildren aged 5-14 years. Urine samples were examined by a filtration method to identify and count S. haematobium eggs, while stool samples were subjected to duplicate Kato-Katz thick smears to quantify eggs of S. mansoni and soil-transmitted helminths. Data on sociodemographic, socioeconomic, and environmental factors were obtained using a pretested questionnaire. Multivariate logistic regression was employed to test for associations between variables. We found a prevalence of S. haematobium of 14.0% (166 of 1187 schoolchildren infected) and a prevalence of S. mansoni of 6.1% (66 of 1089 schoolchildren infected). In the southern part of Côte d'Ivoire, the prevalence of S. haematobium was 16.1% with a particularly high prevalence observed in Sikensi (35.6%), while S. mansoni was most prevalent in Agboville (11.2%). Swimming in open freshwater bodies was the main risk factor for S. haematobium infection (adjusted odds ratio (AOR) = 127.0, 95% confidence interval (CI): 25.0-634.0, p < 0.001). Fishing and washing clothes in open freshwater bodies were positively associated with S. haematobium and S. mansoni infection, respectively. Preventive chemotherapy using praziquantel should be combined with setting-specific information, education, and communication strategies in order to change children's behavior, thus avoiding contact with unprotected open freshwater.

Antiplasmodial activity of two medicinal plants against clinical isolates of Plasmodium falciparum and Plasmodium berghei infected mice.

Malaria is an infectious and deadly parasitic disease, associated with fever, anaemia and other ailments. Unfortunately the upsurge of plasmodium multidrug resistant constrained researchers to look for new effective drugs. Medicinal plants seem to be an unquenchable source of bioactive principles in the treatment of various diseases. The aim of this study was to assess the antiplasmodial activity of two Ivorian medicinal plants. The in vitro activity was evaluated against clinical isolates and Plasmodium falciparum K1 multidrug resistant strain using the fluorescence based SYBR green I assay. The in vivo bioassay was carried out using the classical 4 day suppressive and curative tests on Plasmodium berghei infected mice. Results showed that the in vitro bioassay of both plant extracts were found to exhibit a promising and moderate antiparasitic effects on clinical isolates (5 µg/mL < IC50 < 15 µg/mL) and Plasmodium falciparum multidrug resistant K1 strain (15 µg/mL < IC50 < 50 µg/mL). Furthermore, the in vivo antiplasmodial screening of both extracts showed a significant decrease in parasitemia, which was dose-dependent. Body temperature in mice treated with both extracts at experimental doses increased, compared to the negative control group and was dose-dependent. As for mice body weight a significant decrease (p < 0.001) was noticed in the negative control group compared to tested groups of animals. The hydroethanolic stem bark extract of Anthocleista djalonensis A Chev and leaves extract of Ziziphus mauritiana Lam exhibited anti-malarial activities. Therefore, the bioactive compounds of both plant extracts need to be investigated.