Mass Screening and Treatment for Reduction of Falciparum Malaria

NCT ID: NCT04093765

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5542 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2020-12-31

Brief Summary

In this project, the investigators aim at an operational research deployment of Ultrasensitive Rapid Diagnostic Test (URDT) -based Mass Screening and Treatment (MSAT) in the Malaria Elimination Task Force (METF) elimination program. This intervention will be tested in two types of setting. In group 1, MSAT will be used in a programmatic setting in order to decrease the reservoir of asymptomatic carriers in high incidence villages (following the same principles and objective as previously deployed MDA interventions). In group 2, the investigators take advantage of the lighter framework of MSAT to use it as a reactive intervention in order to respond to malaria outbreaks in low to intermediate incidence villages. The MSAT intervention will be preceded with community-level consent and community engagement (CE) activities. MSAT will be conducted over a period of approximately 1 week in each hamlet, village or group of villages, and will consist in administering a P. falciparum URDT to all individuals agreeing to participate. A limited subgroup (expected 5-25%) will be found positive and receive supervised treatment over 3 days for the standard regimen (DP to cure asexual stage infection + single low-dose primaquine to destroy gametocytes). After this intervention, the incidence of clinical falciparum episodes will be monitored by the village MP. In group 1, a comparison of the prevalence at baseline and 12 months after MSAT intervention will be performed through a second URDT survey, in addition to which both baseline and 12-month surveys will include the collection of a 200µL capillary blood sample for reference detection in the laboratory.

The intervention will be evaluated primarily on its ability to reduce yearly cumulative incidence of clinical falciparum malaria compared to year before intervention. Additional evaluations of the impact of MSAT will include: in group 1, comparison of asymptomatic infection prevalence; and in group 2, modifications of the shape of the incidence curve following intervention.

Funder: Wellcome Trust grant reference 106698/B/14/Z

Detailed Description

STUDY DESIGN

Stepped-wedge open-label, non-randomized, cluster intervention.

This study will be performed in clusters (hamlet (isolated group of household, village, or group of village). The intervention will be conducted in two types of clusters, both corresponding to locations where an excess of case was detected.

Group 1: Sustained high incidence clusters, characterized by a yearly cumulative incidence >84 cases/1000/year

Villages in group 1 will be attributed an intervention a given year based on the cumulative incidence over the previous 12 months (METF stratification January, including the last 2 transmission seasons). The order of intervention will be decided based on logistic constraints and highest incidence.

Group 2: Focal transmission clusters, corresponding to locations where an epidemic alert has been signalled and confirmed (see definition of thresholds).

Villages in group 2 will be attributed an intervention based on P. falciparum incidence in the previous 4 weeks. In near-0 transmission area, an intervention will be conducted in each likely source location of transmission of a locally acquired case. In the other areas (METF1+METF2), the intervention will be triggered when the incidence is above the pre-defined epidemic threshold.

In each cluster, all inhabitants will be invited to undergo an URDT test to identify their infection status, and will receive the appropriate treatment according to their characteristics. Information on village inhabitants absent during the MSAT activities will be obtained from village population lists provided by the village headman and from household member declarations. During the URDT screening, all individuals will receive a unique identifying number that will be used to record demographic data in the MSAT paper logbook and to label URDT and reference sample.

Before and after MSAT intervention, incidence of clinical malaria episodes will be recorded at the MP (1 or several) serving the cluster receiving the intervention. No individual data will be collected to link clinical case participation, infection status and incidence of clinical episodes.

Participants from group 1 clusters will be invited to participate in a prevalence survey during MSAT and 12 months after, in order to evaluate the impact of the MSAT campaign on the asymptomatic carriage prevalence. This will require collection of a 200µL sample during the MSAT campaign and a second round of URDT screening with the collection of a 200µL sample, 12 months after MSAT.

STUDY PARTICIPANTS

Populations of villages with high P. falciparum incidence located in Eastern Kayin State, Myanmar.

SUMMARY RESULTS

In 2018, two rounds of mass screening and treatment (MSAT) using ultrasensitive RDT (hsRDT) were conducted in 17 villages. The first round was carried out in 10 villages. Despite relatively high screening numbers with an average village screening coverage of 80.5% (min= 74.2%, max= 86%), equivalent to 1,364 people in total, only 1.1% of those screened were P. falciparum positive by hsRDT (ultrasensitive malaria RDT). In the second round of MSAT, 6 villages in underwent hsRDT screening. Screening numbers in this round were lower than in round 1 with an average of 70% (min= 47.1%, max= 90.8%) of villagers screened, or 1,104 people in total, however a higher positivity rate by hsRDT was detected with 5.38% of all tests returning a positive P. falciparum result.

In 2019, MSAT was conducted in 12 villages. This round had a high hsRDT screening coverage with an average coverage of 95% (min = 92%, max= 98%) in 12 villages, equivalent to 3,074 people. However, only 2.67% of hsRDTs returned a positive result for P. falciparum.

The primary intervention and outcome were completed in 31th Dec 2019. During the observation period post MSAT period in 2020. We have found the limited evidence for sustained impact of MSAT at low levels of P. falciparum detection in following post MSAT months by using hsRDT.

Conditions

Plasmodium Falciparum Malaria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Sustained high incidence villages

Villages classified as high incidence, low probability of elimination (P. falciparum cumulative incidence \>84 cases/1000/year, in spite of \>1 year of functioning malaria post) will be eligible to be included in group 1. Villages in this group will be addressed by MSAT waves of 10-15 villages. Interventions will consist of 1 Ultrasensitive Rapid Diagnostic Test (URDT) and antimalarials drugs.

Group Type: EXPERIMENTAL

Ultrasensitive Rapid Diagnostic Test (URDT)

Intervention Type: DIAGNOSTIC_TEST

Investigation will consist in 1 URDT.

For P. falciparum URDT positive:

• collection of 3x1cm dried blood spots on filter paper
• administration of a supervised antimalarial treatment course to individuals for which a P. falciparum will have been detected by URDT.

Specifically in group 1, a population list will be collected in each village prior to MSAT campaign and all participants will undergo:

• collection of a 200 µL-aliquot of capillary blood for each participant to the screening during the MSAT intervention.
• 1 URDT + collection of a 200µL-aliquot of capillary blood for each participant to the follow-up survey at M12.

Antimalarials

Intervention Type: DRUG

A safe, recommended treatment of P. falciparum malaria will be administered to URDT positive individuals based on participant's characteristics:

• The standard regimen for participants without known antimalarial allergy, not pregnant and not breastfeeding, will be a 3-day supervised weight-adjusted DP course and a single low dose PMQ. The single low dose PMQ will be administered on the first day.
• Pregnant women and in their 2nd or 3rd trimester, and breastfeeding mothers, will receive a DP course but no PMQ.
• Pregnant women in their first trimester will receive an oral course of quinine+clindamycin (7 days).
• Individuals with known drug allergy to piperaquine will be treated with AL (+/- sld PMQ as per their pregnancy/breastfeeding status)
• Specific/complex cases will be assessed by a medic and referred to a health facility for treatment if necessary.

Seasonal focal transmission villages/locations

This group will follow the NMCP case/and foci investigation guidelines, but use URDT instead of standard RDT for screening. MSAT group 2 locations will be cluster of houses, villages or clusters of villages selected based on the results of case or foci/outbreak investigation. Interventions will consist of 1 Ultrasensitive Rapid Diagnostic Test (URDT) and antimalarials drugs.

• Village inclusion after case investigation
• Village inclusion after outbreak investigation

Group Type: EXPERIMENTAL

Ultrasensitive Rapid Diagnostic Test (URDT)

Intervention Type: DIAGNOSTIC_TEST

Investigation will consist in 1 URDT.

For P. falciparum URDT positive:

• collection of 3x1cm dried blood spots on filter paper
• administration of a supervised antimalarial treatment course to individuals for which a P. falciparum will have been detected by URDT.

Specifically in group 1, a population list will be collected in each village prior to MSAT campaign and all participants will undergo:

• collection of a 200 µL-aliquot of capillary blood for each participant to the screening during the MSAT intervention.
• 1 URDT + collection of a 200µL-aliquot of capillary blood for each participant to the follow-up survey at M12.

Antimalarials

Intervention Type: DRUG

A safe, recommended treatment of P. falciparum malaria will be administered to URDT positive individuals based on participant's characteristics:

• The standard regimen for participants without known antimalarial allergy, not pregnant and not breastfeeding, will be a 3-day supervised weight-adjusted DP course and a single low dose PMQ. The single low dose PMQ will be administered on the first day.
• Pregnant women and in their 2nd or 3rd trimester, and breastfeeding mothers, will receive a DP course but no PMQ.
• Pregnant women in their first trimester will receive an oral course of quinine+clindamycin (7 days).
• Individuals with known drug allergy to piperaquine will be treated with AL (+/- sld PMQ as per their pregnancy/breastfeeding status)
• Specific/complex cases will be assessed by a medic and referred to a health facility for treatment if necessary.

Interventions

Ultrasensitive Rapid Diagnostic Test (URDT)

Investigation will consist in 1 URDT.

For P. falciparum URDT positive:

• collection of 3x1cm dried blood spots on filter paper
• administration of a supervised antimalarial treatment course to individuals for which a P. falciparum will have been detected by URDT.

Specifically in group 1, a population list will be collected in each village prior to MSAT campaign and all participants will undergo:

• collection of a 200 µL-aliquot of capillary blood for each participant to the screening during the MSAT intervention.
• 1 URDT + collection of a 200µL-aliquot of capillary blood for each participant to the follow-up survey at M12.

Intervention Type: DIAGNOSTIC_TEST

Antimalarials

A safe, recommended treatment of P. falciparum malaria will be administered to URDT positive individuals based on participant's characteristics:

• The standard regimen for participants without known antimalarial allergy, not pregnant and not breastfeeding, will be a 3-day supervised weight-adjusted DP course and a single low dose PMQ. The single low dose PMQ will be administered on the first day.
• Pregnant women and in their 2nd or 3rd trimester, and breastfeeding mothers, will receive a DP course but no PMQ.
• Pregnant women in their first trimester will receive an oral course of quinine+clindamycin (7 days).
• Individuals with known drug allergy to piperaquine will be treated with AL (+/- sld PMQ as per their pregnancy/breastfeeding status)
• Specific/complex cases will be assessed by a medic and referred to a health facility for treatment if necessary.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All persons living in the village or cluster of villages will be eligible for MSAT intervention.
• Individuals living in smaller settlements (permanent or temporary) within walking distance of a selected intervention village will also be eligible.
• Large "work-related" settlements in the vicinity of a targeted village (military camps, logging camp, mining site) will be approached by the team to be included in the screening and treatment activity. They will be included in the analysis as a unit within a cluster of villages if all the study information can be collected (including follow-up survey for Group 1).

Exclusion Criteria

• Individuals who do not provide informed consent for both URDT screening and treatment in case of positive result. Individuals will be given the possibility to refuse the collection of the 200µL reference sample or the DBS collection but participate to URDT screening and treatment.
• Children <1 year old
• Individuals with a documented Pf-positive malaria RDT who received treatment (AL+sld PMQ) during the previous 7 days.

NB: Individuals who were diagnosed infected with PF and received a treatment between 7 and 30 days before the intervention are still likely to be URDT positive due to the persistence of HRP2, and this will result in treatment of individuals who are likely uninfected. However, in a high prevalence area or in an outbreak context, previous infection signals exposure, and DP will provide a protection against a likely re-infection.

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

francois Nosten, PhD

Role: PRINCIPAL_INVESTIGATOR

Shoklo Malaria Research Unit

Locations

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, Thailand

Countries

Thailand

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MAL17011

Identifier Type: -

Identifier Source: org_study_id