Uncomplicated P. falciparum malaria Infections and Infestations Uncomplicated Plasmodium falciparum malaria
Conditions
Interventions
The choice of study drugs has been made deliberately in response to the needs of each country in malarial treatment particularly with the need to provide treatment beyond the formal public sector and
Sponsors
Rwanda Biomedical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 1 to 14 years 2. A slide-confirmed mono-infection of P. falciparum, asexual parasitemia between 1000 and 100000 p/ul 3. Able to attend follow-up visits 4. Written informed consent provided by parent or guardian. If the parent/caretaker is illiterate, a witness’ signature and the thumbprint of the participant’s parent/caretaker will be required.
Exclusion criteria
Exclusion criteria: 1. Severe malnutrition 2. Co-morbidity including but not limited to: infection, severe anaemia, epilepsy, abnormal cardiac rhythm, hypoglycemia, jaundice, respiratory distress, and recent history of allergy, 3. Presence of danger signs including: an inability to drink, vomiting in the past 24 h, an axillary temperature of > 37.5°C or rectal/tympanic temp > 38.0°C, a history of fever within past 24 hours, and/or a recent history of multiple convulsions, unconsciousness, inability to stand or sit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PCR-unadjusted and PCR-adjusted adequate clinical and parasitological response (ACPR) at 28 and 42 days follow-up. ACPR, Early treatment failure (ETF), late parasitological failure (LPF), and late clinical failure (LCF) will be classified in accordance with the WHO protocol. A participant will be considered as experiencing ACPR if they are not classified as experiencing ETF, LPR or LCF. Parasite clearance will be determined from Giemsa-stained blood films on day 2 and day 3. Blood smears will be taken at baseline, 1, 2, 3, 7, 14, 21, 28, 42 and 68 days. Trained microscopy technicians will quantify asexual parasites on thick smears (per 8000 white blood cells) and thin smears will be used for species identification. A minimum of 100 fields will be read before slides were deemed parasite negative. Each slide will be assessed independently by two microscopy technicians at each health centre and a geometric mean parasite density will be calculated. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Adverse events on CoArtem® and Duo-cotexin® assessed through serious adverse event forms completed by the investigators by 68 days follow-up 2. Proportion of parasites associated with molecular markers related to reduced susceptibility to Duo-cotexin® and CoArtem® assessed through dried filter paper blood spots from patients at baseline and from patients with parasite recurrence on day 7 and onwards if necessary (at 14, 21, 28, 42, and 68 days). These will be placed in a 96-well plate, lysed overnight in a saponin solution and DNA will be extracted with the InstaGene Matrix resin (Bio-Rad, Hercules, CA, USA) as described previously by Canier et al. DNA samples from day 0 and from the day of parasite recurrence will be analysed for genotyping of msp1, msp2 (merozoite surface proteins 1 and 2) and glurp. Mutations in the propeller domain of PfKelch13 (PF3D7_1343700, codons 440–680, 720 bp), associated with resistance to artemisinin, will be identified by capillary sequencing of PCR products, as described by Menard et al, NEJM 2016. 3. Post-treatment gametocytaemia & malaria transmission will be assessed by quantitative nucleic acid sequence-based amplification (QT-NASBA) and real-time molecular beacon detection. The multiplex assay will consist of both 18s rRNA QT-NASBA to quantify P. falciparum and pfs25 mRNA QT-NASBA to specifically quantify mature gametocytes at baseline, 1, 2, 3, 7, 14, 21, 28, 42 and 68 days | — |
Countries
Rwanda
Outcome results
None listed