Serological Screen and Treat Trial for Plasmodium Vivax
- Conditions
- Malaria, Vivax
- Interventions
- Diagnostic Test: Serological screen and treat
- Registration Number
- NCT04223674
- Lead Sponsor
- Indonesia University
- Brief Summary
This is a clinical trial to evaluate an experimental serological diagnostic technique intended to identify people at high risk of having dormant malaria parasites in their liver. The study is designed to evaluate the efficacy of serological screening vs. routine care for the prevention of recurrent P. vivax infections. A total of 960 schoolchildren will be randomized into the interventional or control arm.
- Detailed Description
This is a randomized controlled trial to evaluate an experimental serological diagnostic technique intended to identify people at high risk of having dormant malaria parasites in their liver. The study is designed to show a superiority of SSAT vs. routine care for the prevention of recurrent P. vivax infections. With the estimated prevalence of 20%, the investigators will have a power of \>90% to detect a significant difference with the sample size of 350 children per group. The investigators will recruit 480 children per group to anticipate subject loss due to exclusion and drop out.
After obtaining informed consent from their parents/legal guardians, 800 schoolchildren living in Batubara regency, North Sumatra, Indonesia, will be individually randomized to intervention (SSAT) or control (routine care) group. During enrollment, all participants will be tested with Pv serological test by standard Luminex, and standard finger stick microscopic. Their hemoglobin (Hb) and Glucose-6-Phosphate Dehydrogenase (G6PD) level will be measured. Children with Hb level\<9 g/dL and/or G6PD \<4 U/g Hb (male) or \<6 U/g Hb (female) will be excluded. In the intervention arm (SSAT), children who are seropositive by standard Luminex and/or symptomatic LMF positive will be treated with dihydroartemisinin-piperaquine (DHA-PP) for 3 days according to national guideline and primaquine/PQ high dose (1 mg/kg BW/day for 7 days for Pv/Po, 0.25 mg/kg BW for Pf). In the control arm, children will be treated only when they show symptoms (body temperature\>=36.5oC or history of fever within last 3 days) and proven positive by LMF. All treatment will be provided under direct supervision by the research team during which any adverse event/severe adverse event will be recorded. Hemoglobin level and urine will be monitored daily for 7 days of PQ administration. Post-hoc qPCR detection will be performed to determine their initial malaria status. Several additional tests will also be performed to all participants during this initial screening: microscopic examination of shallow vasculature of the ankle (light microscopy-skin/LMS), magneto-optical detection of hemozoin, and post-hoc point-of-care/POC serological test.
After enrollment, all children will be actively followed for 9 months every 4 weeks for post-hoc assessment by qPCR. Anytime during this follow up period, children becoming acutely ill will be tested for malaria by LMF, and referred to Primary Health Center to receive treatment when positive. Furthermore, household members of these infected children will also be screened for malaria infection by LMF and post-hoc LMS and qPCR. This family screening will be performed by 2x house visit (7-10 AM and 7-10 PM). Treatment will be given for those found positive by LMF regardless of their symptoms. Antimalarial treatment provided during this follow up period will be according to national standard guideline: 3 days of DHA-PP plus PQ (single 0.25 mg/kg BW dose for Pf, daily 0.25 mg/kg BW dose for 14 days for Pv/Po).
At the end of study, Pv serological test and LMF will be performed to all schoolchildren. Those found positive by LMF will be referred to Primary Health Center to receive treatment according to national standard guideline.
Sponsor: WEHI, Funding: NHMRC, Grant number: GNT1102297
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1133
- resident of study area and attending selected elementary school in Grade 1-5 or middle school Grade 1-3
- no evidence of health condition that would interfere with study participation
- assent of child and documented parental informed consent
- G6PD deficiency as determined by SD Biosensor quantitative determination of <70% G6PD activity (<6 U/g Hb).
- Haemoglobin < 9 g/dL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Serological screen and treat Serological screen and treat Children who screened with sero test and microscopy. A 7-day high dose PQ will be provided for those with Pv seropositive regardless of their symptoms and symptomatic children with microscopic Pv/Po positive.
- Primary Outcome Measures
Name Time Method Incidence reduction 9 month of follow up Difference of P. vivax incidence by PCR between children serologically screened and those receiving routine care.
- Secondary Outcome Measures
Name Time Method Seroconversion rate 9 month Seroconversion rate before and after intervention in SSAT and control arms.
Time-to recur 9 month Difference in the time-to recur of P. vivax by PCR in SSAT and control arms.
Adverse event and severe adverse event 9 month Adverse event (AE) and Severe Adverse Event (SAE) of high dose PQ in schoolchildren.
Sahli Hb One month Hb level in Sahli's method, Standard G6PD (SD Biosensor Inc., ROK) in comparison with (HemoCue AB, Angelholm, Sweden).
Gametocyte duration 9 month Mean duration time of gametocyte in LMS and LMF
Recurrent symptomatic P. vivax 9 month Difference in the incidence of recurrent symptomatic P. vivax by microscopy in SSAT vs control arms
Recurrence number 9 month Difference in the number of recurrent P. vivax by PCR in SSAT vs. control arms
point-of-care assay performance one month Sensitivity and specificity of point-of-care antibody detection test vs. gold standard Luminex assay
Hemozoin detection One month Sensitivity and specificity of magneto-optical hemozoin detection (MOD) compared to standard malaria detection and PCR.
Skin gametocyte 9 month Sensitivity and specificity of microscopic examination to detect parasitemia from the shallow skin vasculature of the ankle (light microscopy-skin/LMS) compared to standard microscopic (light microscopy-finger/LMF) and PCR.
Trial Locations
- Locations (1)
Tanjung Tiram Primary Health Center
🇮🇩Tanjung Tiram, Batubara, Indonesia