Clinical trial NCT04093765: Mass Screening and Treatment for Reduction of Falciparum Malaria
Official title: Operational Evaluation of Mass Screening and Treatment Using Ultrasensitive Rapid Detection Tests to Reduce P. Falciparum Incidence in a Malaria Elimination Program in Eastern Kayin State, Myanmar
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Plasmodium Falciparum Malaria
Keywords: Ultrasensitive Rapid Diagnostic Test
Mass Screening and Treatment
Greater Mekong Subregion
Malaria Elimination Task Force
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2019-09-18
Enrollment: 5542
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

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.

Primary outcomes:
measure: Adjusted incidence rate ratio before/after MSAT
timeFrame: 12 month
Secondary outcomes:
measure: Prevalence of P. falciparum infection measured in the village by URDT and by reference method (group 1)
timeFrame: 12 months
measure: Change in the incidence dynamics over the transmission season (group 2)
timeFrame: 3 years
measure: The percentage of participant among village resident tested by URDT.
timeFrame: 3 years
measure: % of P. falciparum positive samples by reference method which were positive by URDT and treated; % of P. falciparum negative samples by reference method which were positive by URDT and treated (group 1)
timeFrame: 3 years
Other outcomes:
measure: Cumulative incidence of falciparum malaria episodes before and after MDA/MSAT; prevalence of falciparum infection before and after MDA/MSAT
timeFrame: 3 years
Locations:
city: Mae Sot
country: Thailand
facility: Shoklo Malaria Research Unit
state: Tak
Study officials:
affiliation: Shoklo Malaria Research Unit
name: francois Nosten, PhD
role: PRINCIPAL_INVESTIGATOR
References: