Malaria
Conditions
Brief summary
This is an in vivo evaluation of drug efficacy performed in Cruzeiro do Sul, in the state of Acre, Brazil. A total of 81 participants ≥5 years old with parasitological confirmation of P. falciparum monoinfection will be treated under supervision with artemether-lumefantrine for three days, with doses according to the Brazilian guidelines for malaria control. The clinical and parasitological parameters will be monitored for a 28-day follow-up period to evaluate the efficacy of the combination therapy. A blood sample will be collected on filter paper on the first day and on the day of suspected failure to try to differentiate the parasite genotypes using techniques based on polymerase chain reactions. The results of this efficacy evaluation on the drug combination will help the Brazilian Ministry of Health to evaluate the national policy for treatment of malaria caused by P. falciparum.
Detailed description
This protocol uses the recommended World Health Organization (WHO) protocol for monitoring antimalarial efficacy. Patients with malaria will receive supervised therapy and will be monitored for 28 days to check for treatment response, both clinically and parasitologically. A total of 81 participants ≥5 years old with parasitological confirmation of P. falciparum monoinfection will be treated under supervision with artemether-lumefantrine for three days, with doses according to the Brazilian guidelines for malaria control. The clinical and parasitological parameters will be monitored for a 28-day follow-up period to evaluate the efficacy of the combination therapy. Patients will be asked to come back on Days 2, 3, 7, 14, 21 and 28 for clinical evaluation and blood tests using microscopy. A blood sample will be collected on filter paper on the first day and on the day of suspected failure to try to differentiate the parasite genotypes using techniques based on polymerase chain reactions, this will allow us to determine if the recurrent infection was reinfection or failure or recrudescence. Results of this evaluation will guide treatment policies in Brazil.
Interventions
This is the sole arm in this study and it is the use of the standard combination therapy for treatment of P. falciparum malaria.
Sponsors
Secretaria Estadual de Saúde do Acre
Ministry of Health, Brazil
Evandro Chagas National Institute of Infectious Disease
Centers for Disease Control and Prevention
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Evaluation of the efficacy of artemether and lumefantrine for uncomplicated P. falciparum malaria.
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* \>= 5 years * body weight \< 120kg * documented fever (axillary temperature ≥37.5o C) or history of fever in the previous 48 hours in the absence of other obvious causes of fever, such as pneumonia, middle ear infection, etc. * monoinfection by P. falciparum with parasitemia between 250 and 200,000 asexual parasites/µl, as determined by swab and thick peripheral blood smear microscopic exam * patient or parent/caregiver able to comprehend and sign informed consent or permission form * patients aged 7-17 years able to provide assent, patients aged 5-6 years do not require assent * willingness to return to the clinic and/or accept home visits for regular check-ups during the 28-day follow-up period * hemoglobin level ≥8 g/dl
Exclusion criteria
* presence of malaria danger signs (inability to drink, vomiting (more than twice in the previous 24 hours), recent history of seizures (one or more in the previous 24 hours), altered level of consciousness, inability to sit or stand up); presence of signs of severe malaria (altered level of consciousness, psychomotor alteration, seizure, torpor and irreversible coma), severe anemia (hematocrit \< 15% or clinical signs, hemoglobin \<5 g/dl), renal failure (serum creatinine \> 3 mg/dl or clinical signs), pulmonary edema, hypoglycemia (blood glucose \< 40 mg/dl or clinical signs), shock (systolic blood pressure \< 70 mmHg for adults; \< 50 mmHg for children), spontaneous hemorrhage/disseminated intravascular coagulation, repeated generalized seizures, acidemia/acidosis (clinical signs), macroscopic hemoglobinuria, and jaundice. * history of chronic or severe underlying diseases (e.g. heart, renal or liver diseases, HIV/AIDS, tuberculosis, malnourishment) * history of hypersensitivity to AL * current pregnancy (history of current pregnancy or positive pregnancy test) * use of any antimalarial drug in the previous 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absence of Malaria Parasites in Blood. | 28 days | Investigators will evaluate the percentage of patients who remain free of malaria parasites in the blood during the 28-day follow-up period. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Artemether-Lumefantrine Three days of standard treatment. This is a standard combination therapy for the treatment of P. falciparum malaria.
Artemether-lumefantrine combination: This is the sole arm in this study and it is the use of the standard combination therapy for treatment of P. falciparum malaria. | 79 |
| Total | 79 |
Baseline characteristics
| Characteristic | Artemether-Lumefantrine |
|---|---|
| Age, Continuous | 30 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 79 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment Brazil | 79 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 79 |
| serious Total, serious adverse events | 0 / 79 |
Outcome results
Primary
Absence of Malaria Parasites in Blood.
Investigators will evaluate the percentage of patients who remain free of malaria parasites in the blood during the 28-day follow-up period.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Artemether-Lumefantrine | Absence of Malaria Parasites in Blood. | 73 Participants |