The proportion of malaria that is the Plasmodium vivax species is increasing in Indonesia. Reducing vivax malaria will require innovative solutions to cure both the blood and liver stages of the disease. This study will evaluate of the feasibility of implementing point-of-care glucose-6-phosphate dehydrogenase deficiency (G6PD) testing. This will be followed by high dose, short course primaquine treatment regimens for patients with vivax malaria, and combined with patient education, surveillance, and pharmacovigilance. We plan to implement the study at 6 health facilities across Indonesia using a staged before-and-after study, with a mixed method evaluation.
Significant gains have been made in reducing the overall burden of malaria worldwide, however these have been far greater for Plasmodium falciparum than P. vivax. P. vivax remains a major obstacle to malaria control and elimination efforts, largely due to its ability to form dormant liver stages (hypnozoites) that allow it to escape detection and treatment. Importantly, they are susceptible only to 8 aminoquinolines such as primaquine however, primaquine is associated with risk of haemolysis in individuals with a genetic condition, called glucose-6-phosphate dehydrogenase (G6PD) deficiency. Additionally, the recommended 14-day prolonged treatment regimen is associated with poor treatment adherence hence ineffective primaquine treatment. Innovative solutions to the radical cure of both the blood and liver stages of P. vivax are urgently required. The Indonesian Ministry of Health has requested a pragmatic study of the feasibility and cost-effectiveness of implementing point-of-care G6PD testing followed by high-dose, short-course primaquine treatment regimens for patients with vivax malaria. These interventions are to be combined with practicable enhancements to patient education, supervision, malariometric surveillance and pharmacovigilance. This will be a before-after longitudinal health facility-based study implemented at six sites in Indonesia; four in Papua, one in North Sumatra and one in Lampung. We will use a staged approach for the implementation of the revised case management strategy, including patient education and counselling,community-based clinical review, with mixed methods evaluation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
2,999
1. Point-of-care quantitative G6PD testing using G6PDSTANDARD (SD Biosensor) prior to use of primaquine (Day 0) 2. Prescription of short course primaquine (7 mg/kg total)(Day 0): * PQ7 (1 mg/kg/day for 7 days) if G6PD activity greater than 70 percent * PQ14 (0.5 mg/kg/day for 14 days) if G6PDactivity is 30-70 percent * PQ8w (0.75 mg/kg/week for 8 weeks) if G6DPactivity less than 30 percent 3. Participant counselling at the health facility (Day 0): * Supervision of first dose of primaquine * Education regarding the importance and risks of primaquine therapy and necessity to take primaquine with food 4. Community based clinical review on Day 3 (and Day 7 for the first 300 participants) to detect and manage gastrointestinal or haemolytic adverse effects of treatment and encourage adherence to full treatment regime 5. Improved malariometric surveillance and pharmacovigilance to support wider scale use of the revised case management
Puskesmas Hanura
Hanura, Lampung, Indonesia
Puskesmas Tanjung Leidong
Labuhanbatu, North Sumatra, Indonesia
Puskesmas Bhintuka
Mimika, Special Region of Papua, Indonesia
Puskesmas Pasar Sentral
Mimika, Special Region of Papua, Indonesia
Puskesmas Timika
Mimika, Special Region of Papua, Indonesia
Puskesmas Wania
Mimika, Special Region of Papua, Indonesia
Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment
SAEs are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks) ]
Proportion of patients experiencing at least one Adverse Event of Special Interest(AESI) during treatment
AESIs (haemolysis, methaemoglobinaemia and gastrointestinal discomfort) are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks)
Proportion of patients with P. vivax malaria who correctly receive all components of the revised case management package
Measured by completion of G6PD testing and the correct prescription of primaquine based on G6PD activity, completion of patients counselling and community based follow up on Day 3
Time frame: 3 days
The proportion of patients with any AESI during treatment
AESIs are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks)
The proportion of patients with a gastrointestinal (GI) AESI during treatment
AESIs are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks)
The proportion of patients with an AESI related to haemolysis during treatment
AESIs are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks) ]
The proportion of patients an AESI related to methaemoglobinaemia
AESIs are collected during clinical review using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks)
Proportion of patients permanently stopping PQ before end of treatment
Discontinuation of PQ will be assessed using a study-specific questionnaire
Time frame: During treatment (up to 8 weeks)
The proportion of patients receiving correct treatment based on G6PD activity
This will be assessed by linking patients G6PD activity results measured during study enrolment with primaquine dose prescribed on the same day
Time frame: 1 day
Proportion of patients who were reviewed on Day 3 and Day 7
This will be assessed by linking patients enrolment data with Day 3 and Day 7clinical review data
Time frame: 1 week
Perception of and experience with new radical cure tools among health care providers and community members
This will be assessed using stakeholder interviews
Time frame: 6 months
Proportion of health care practitioners who comply with the revised radical cure treatment algorithm
The outcome will be assessed from patients' enrolment data
Time frame: 1 day
Proportion of patients receiving a SD Biosensor G6PD test
The outcome will be assessed from patients' enrolment data
Time frame: 1 day
Proportion of eligible P. vivax malaria patients receiving the correct dose of primaquine based on the result of the G6PD test
The outcome will be assessed from patients' enrolment data
Time frame: 1 day
Proportion of P. vivax malaria patients who are ineligible for daily primaquine and are incorrectly given primaquine (including infants, pregnant females and G6PD deficient patients
The outcome will be assessed from patients' enrolment data
Time frame: 1 day
Proportion of P. vivax malaria patients that are reviewed on Day 3
This will be assessed by linking patients' enrolment data with clinical review data
Time frame: 3 days
Proportion of P. vivax malaria patients that adhere to their prescribed primaquine regimen
This will be assessed by linking patients' enrolment data with clinical review data
Time frame: 3 days
Factors influencing acceptability and feasibility of the new radical cure tools among health care providers are identified
This will be assessed using stakeholder interviews, observations and focus groups
Time frame: 3 days
Barriers and enablers of uptake and implementation at the sub-national levels are identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Factors influencing compliance with G6PD testing and perceptions of new drug regimens and serious adverse events among health care providers are identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Required knowledge, skills, and training to administer the revised case management and patient-counselling identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Factors influencing the barriers and facilitators to patient adherence to primaquine after the rollout of the revised case management identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Perceptions of the new radical cure tools and serious adverse events at the community level identified
This will be assessed using stakeholder interviews and focus groups
Time frame: 18 months
Local acceptability of the revised case management algorithms among patients, their families, and healthcare workers established
This will be assessed using stakeholder interviews and focus groups
Time frame: Day 3
The monthly incidence of confirmed symptomatic P. vivax malaria episodes (mono-infection or mixed) before implementation versus after implementation
This will be assessed by comparing facility surveillance data before implementation with facility surveillance data after implementation
Time frame: 18 months
The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation
This will be assessed by comparing cross-sectional data on n=200 patients (per facility) collected before implementation to the prevalence collected in n=200patients (per facility) after implementation
Time frame: 18 months
Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months
This will be assessed by linking patients' enrolment data
Time frame: 18 months
Costs of implementing policy from a healthcare provider perspective, including health systems strengthening processes
This will be assessed from health system data collected throughout the study
Time frame: 18 months
Household costs per P. vivax episode
This will be assessed from a household cost survey on a subset of patients
Time frame: 3 days
Overall cost-effectiveness of changing policy if revised case management is effective
This will be assessed from health system data collected throughout the study
Time frame: 18 months
Cost per episode of P. vivax malaria from the healthcare provider and societal perspectives
This will be assessed from health system data collected throughout the study
Time frame: 18 months
Cost per component of the revised case management package
This will be assessed from health system data collected throughout the study
Time frame: 18 months
If revised case management package is effective (significantly reduces the incidence of malaria), then the cost-effectiveness of implementing the revised case management as compared with usual care
This will be assessed from health system data collected throughout the study
Time frame: 18 months
Proportion of CHWs who correctly act on early signs of haemolytic anaemia and GI events (i.e. refer patients for further medical review, instruct patient to discontinue treatment)
This will be assessed from clinical review data and study-specific questionnaire
Time frame: 3 days
Number of patients with an SAE who are identified by community or clinic staff follow-up and referred to hospital for further management
This will be assessed by linking clinical review data, study specific questionnaire and SAE form
Time frame: During treatment (up to 8 weeks)
The proportion of patients eligible to receive PQ who had a SAE during treatment
This will be assessed by linking enrolment data, clinical review, study specific questionnaire and SAE form
Time frame: During treatment (up to 8 weeks)
Prevalence of severe anaemia in patients presenting with fever before and after implementation
This will be assessed by comparing the facility surveillance data before implementation with facility surveillance data after implementation
Time frame: 18 months
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