Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021.

Background: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Togo. This study assessed the efficacy of these combinations, the proportion of Day3-positive patients (D3 +), the proportion of molecular markers associated with P. falciparum resistance to anti-malarial drugs, and the variable performance of HRP2-based malaria rapid diagnostic tests (RDTs).

Genetic differentiation of Plasmodium vivax duffy binding protein in Ethiopia and comparison with other geographical isolates.

Background: Plasmodium vivax Duffy binding protein (PvDBP) is a merozoite surface protein located in the micronemes of P. vivax. The invasion of human reticulocytes by P.

Drug-induced stress mediates ring-stage growth arrest and reduces parasite susceptibility to artemisinin.

During blood-stage infection, parasites are constantly exposed to a range of extracellular stimuli, including host molecules and drugs such as artemisinin derivatives, the mainstay of artemisinin-based combination therapies currently used as first-line treatment worldwide. Partial resistance of to artemisinin has been associated with mutations in the propeller domain of the gene, resulting in a fraction of ring stages that are able to survive exposure to artemisinin through a temporary growth arrest. Here, we investigated whether the growth arrest in ring-stage parasites reflects a general response to stress.

Plasmodium falciparum ring-stage plasticity and drug resistance.

Malaria is a life-threatening tropical disease caused by parasites of the genus Plasmodium, of which Plasmodium falciparum is the most lethal. Malaria parasites have a complex life cycle, with stages occurring in both the Anopheles mosquito vector and human host. Ring stages are the youngest form of the parasite in the intraerythrocytic developmental cycle and are associated with evasion of spleen clearance, temporary growth arrest (TGA), and drug resistance.

Assessing the histidine-rich protein 2/3 gene deletion in Plasmodium falciparum isolates from Burkina Faso.

Background: Dual hrp2/hrp3 genes deletions in P. falciparum isolates are increasingly reported in malaria-endemic countries and can produce false negative RDT results leading to inadequate case management. Data on the frequency of hrp2/hrp3 deleted parasites are rarely available and it has become necessary to investigate the issue in Burkina Faso.

Prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine before and after community delivery of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa: a multi-country evaluation.

Background: The effectiveness of community delivery of intermittent preventive treatment (C-IPT) of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine has been evaluated in selected areas of the Democratic Republic of the Congo, Madagascar, Mozambique, and Nigeria. We aimed to assess the effect of C-IPTp on the potential development of Plasmodium falciparum resistance to sulfadoxine-pyrimethamine, since it could threaten the effectiveness of this strategy.

Methods: Health facility-based cross-sectional surveys were conducted at baseline and 3 years after C-IPTp implementation in two neighbouring areas per country, one with C-IPTp intervention, and one without, in the four project countries.

Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea.

Background: Although the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in on the continent is troubling, given the lack of alternative treatments.

Methods: In this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate-amodiaquine or artemether-lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance.

Background: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Chad. This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3 positive patients, proportions of molecular markers associated with P. falciparum resistance to anti-malarial drugs and variable performance of HRP2-based malaria rapid diagnostic tests (RDTs).

Plasmodium falciparum drug resistance-associated mutations in isolates from children living in endemic areas of Burkina Faso.

Background: Artemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used for the preventive treatment of pregnant women (IPTp), while SP plus amodiaquine (SP-AQ) is recommended for children under five in seasonal malaria chemoprevention (SMC). This study aimed to assess the proportions of mutations in the P.

Potential hidden Plasmodium vivax malaria reservoirs from low parasitemia Duffy-negative Ethiopians: Molecular evidence.

Background: The interaction between the Plasmodium vivax Duffy-binding protein and the corresponding Duffy Antigen Receptor for Chemokines (DARC) is primarily responsible for the invasion of reticulocytes by P. vivax. The Duffy-negative host phenotype, highly prevalent in sub-Saharan Africa, is caused by a single point mutation in the GATA-1 transcription factor binding site of the DARC gene promoter.

Polymorphism analysis of drug resistance markers in Plasmodium falciparum isolates from Benin.

Like most countries in sub-Saharan African countries, Benin continues to bear a heavy malaria burden. In 2014, the National Malaria Control Programme (NMCP) changed its treatment policy, and recommended the use of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated Plasmodium falciparum cases. The study presented here was conducted to investigate the impact of current antimalarial drug resistance on the country.

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

Background: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.

Methods: Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA).

Modified Plasmodium falciparum Ring-Stage Survival Assay with ML10 Kinase Inhibitor.

The ring-stage survival assay is the reference assay to measure Plasmodium falciparum artemisinin partial resistance. The main challenge of the standard protocol is to generate 0-to-3-h postinvasion ring stages (the stage least susceptible to artemisinin) from schizonts obtained by sorbitol treatment and Percoll gradient. We report here a modified protocol facilitating the production of synchronized schizonts when multiple strains are tested simultaneously, by using ML10, a protein kinase inhibitor, that reversibly blocks merozoite egress.

Differential transmissibility to Anopheles arabiensis of Plasmodium vivax gametocytes in patients with diverse Duffy blood group genotypes.

Background: Measuring risk of malaria transmission is complex, especially in case of Plasmodium vivax. This may be overcome using membrane feeding assays in the field where P. vivax is endemic.

Ring-stage growth arrest: Metabolic basis of artemisinin tolerance in .

The emergence and spread of artemisinin-tolerant malaria parasites threatens malaria control programmes worldwide. Mutations in the propeller domain of the Kelch13 protein confer artemisinin resistance (ART-R). ART-R is linked to the reduced susceptibility of temporary growth-arrested ring-stage parasites, but the metabolic mechanisms remain elusive.

Vivax malaria in Duffy-negative patients shows invariably low asexual parasitaemia: implication towards malaria control in Ethiopia.

Background: The increase in detections of Plasmodium vivax infection in Duffy-negative individuals in Africa has challenged the dogma establishing the unique P. vivax Duffy Binding Protein-Duffy antigen receptor for chemokines (PvDBP-DARC) pathway used by P. vivax merozoites to invade reticulocytes.

Protein undernutrition reduces the efficacy of praziquantel in a murine model of Schistosoma mansoni infection.

Background: Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel.

Mutations in Huambo, Angola.

Artemisinin (ART) is recommended as the first-line drug for infections combined with a long-acting partner drug. The emergence of resistance to ART (ARTR) is a concern for malaria. The most feared threat remains the spread of ARTR from Southeast Asia to Africa or the independent emergence of ARTR in Africa, where malaria accounts for 93% of all malaria cases and 94% of deaths.

Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018).

The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection.

Background: One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice.

Compensating P. falciparum artemisinin resistance.

Amino acid deprivation from reduced hemoglobin degradation in Pfkelch13 artemisinin-resistant parasites reduces fitness. In this issue of Cell Host & Microbe, Mesén-Ramírez et al. decipher the role of nutrient permeable channel activity within the parasitophorous vacuolar membrane to compensate for this fitness cost in asexual blood-stage Plasmodium falciparum parasites.

Long-term shedding of viable SARS-CoV-2 in kidney transplant recipients with COVID-19.

The exact duration of viable SARS-CoV-2 shedding in kidney transplant recipients (KTRs) remains unclear. Here, we retrospectively investigated this issue using cell cultures of SARS-CoV-2 RT-PCR-positive nasopharyngeal samples (n = 40) obtained from 16 KTRs with symptomatic COVID-19 up to 39 days from symptom onset. A length of viable SARS-CoV-2 shedding >3 weeks from the onset of symptoms was identified in four KTRs (25%).