Clinical trial NCT04053907: P. Falciparum Infection Dynamics and Transmission to Inform Elimination
Official title: P. Falciparum Infection Dynamics and Transmission to Inform Elimination
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malaria
Keywords: falciparum
gametocyte
elimination
anopheles
transmission
diagnostic
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Medical Research Council Unit, The Gambia
name: National Malaria Control Programme, The Gambia
name: Radboud University Medical Center
name: University of California, San Francisco
name: Institute for Disease Modeling
First posted: 2019-08-13
Enrollment: 4000
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: In the current study, three experimental approaches aiming at reducing malaria transmission will be tested. The study will cover two transmission season (2019 and 2020) and the interventions will vary by season. More specifically, in the 2019 transmission season (June-December) (Year 1), community case management of malaria (CCM) will be implemented in all eight villages as improved standard of care; in the 2020 transmission season (Year 2), the eight study villages will be divided into 4 study arms. CCM will continue in all villages; two villages will continue with CCM only (Arm 1, control); the three other pairs of villages will receive active fever screening and treatment (Arm 2); monthly mass screening and treatment (MSAT) (Arm 3); and mass drug administration (MDA) during the last 3 months of the dry season (April-June) (Arm 4). For MDA, the whole population (except for those not fulfilling the entry criteria) will be treated with a full course of dihydroartemisinin-piperaquine (DP) (320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet) per manufacturer's guidelines (once daily for 3 days and according to body weight). The MDA treatment will be repeated 3 times at monthly intervals.

Detailed description: In the current study, the investigators will first improve access to care in all villages by implementing community-based clinical case management (CCM) (year 1). In this year, the investigators will quantify gametocyte carriage and transmission from clinical cases passively recruited by CCM, and gametocyte carriage and transmission from asymptomatic infections detected in community surveys. These data will support the interpretation of the main study outcomes in year 2 when the investigators will directly compare the effect of CCM on the human reservoir of infection as compared to three different approaches, namely i) active fever screening and treatment that should detect symptomatic infections for early treatment; ii) Mass Screening and Treatment (MSAT) that will systematically screen, using point-of-care diagnostics, the whole population, with infected individuals immediately treated; and iii) mass drug administration (MDA) that will treat the whole population with a full course of an antimalarial treatment.

Eligibility criteria: Inclusion Criteria:

1. Resident in the village.
2. Willingness to participate in repeated assessments of health and infection status and to donate a maximum of 30 mL (milliliter) of blood (children \<5 years of age), 37 mL (milliliter) of blood (children \<10 years of age) or 52 mL (milliliter) of blood (older individuals) during an 18-month period.

Exclusion Criteria:

1. Any chronic illness that would affect study participation.
2. Pre-existing severe chronic health conditions
3. History of intolerance to artemether-lumefantrine.
4. Participants \< 6months old and pregnant women in the first trimester (only for Arm with MDA-DP treatment).
5. Hypersensitivity to DP (only for Arm with MDA-DP treatment).
6. Taking drugs that influence cardiac function or prolong QTcorrected interval (only for Arm with MDA-DP treatment).

Primary outcomes:
measure: Parasite prevalence by molecular detection at the end of study (cross-sectional survey).
timeFrame: 16 weeks
measure: Parasite density by molecular detection at the end of study (cross-sectional survey).
timeFrame: 16 weeks
Secondary outcomes:
measure: Gametocyte prevalence by molecular methods at the end of study (cross-sectional survey).
timeFrame: 16 weeks
measure: Gametocyte density by molecular methods at the end of study (cross-sectional survey).
timeFrame: 16 weeks
measure: Gametocyte prevalence of male and female gametocytes by molecular methods among P. falciparum infections at all study visits.
timeFrame: Throughout study, an average of 18 months
measure: Gametocyte density of male and female gametocytes by molecular methods among P. falciparum infections at all study visits.
timeFrame: Throughout study, an average of 18 months
measure: Incidence of malaria infections
timeFrame: Throughout study, an average of 18 months
measure: Infectivity of P. falciparum infections to mosquitoes
timeFrame: Throughout study, an average of 18 months
Other outcomes:
measure: The detectability of infections by highly-sensitive rapid diagnostic tests related to histidine rich protein-2 (HRP2) concentrations.
timeFrame: Throughout study, an average of 18 months
measure: The detectability of infections by highly-sensitive rapid diagnostic tests related to duration of infection.
timeFrame: Throughout study, an average of 18 months
measure: The detectability of infections by rapid diagnostic tests related to duration of infection.
timeFrame: Throughout study, an average of 18 months
measure: The detectability of infections by highly-sensitive rapid diagnostic tests related to parasite density by molecular diagnostics.
timeFrame: Throughout study, an average of 18 months
measure: The detectability of infections by rapid diagnostic tests related to parasite density by molecular diagnostics.
timeFrame: Throughout study, an average of 18 months
measure: The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte density.
timeFrame: Throughout study, an average of 18 months
measure: The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte sex-ratio.
timeFrame: Throughout study, an average of 18 months
measure: The effect of infection characteristics (clonal parasite infection) on the transmissibility of infections to mosquitoes.
timeFrame: Throughout study, an average of 18 months
measure: Gametocyte sex-ratio on the transmissibility of infections to mosquitoes.
timeFrame: Throughout study, an average of 18 months
measure: The impact of human haemoglobinopathies on the transmissibility of infections to mosquitoes.
timeFrame: Throughout study, an average of 18 months
measure: Mean fluorescence intensity (MFI) to inflammatory markers and naturally acquired antibody responses to gametocyte antigens on the transmissibility of infections to mosquitoes.
timeFrame: Throughout study, an average of 18 months
measure: Relationship between total parasite density (parasite/µL) and gametocyte density (gametocytes/µL)
timeFrame: Throughout study, an average of 18 months
measure: Malaria transmission potential based on measured gametocyte densities (gametocytes/µL).
timeFrame: Throughout study, an average of 18 months
measure: Number of acquired parasite clones based on genotyping.
timeFrame: Throughout study, an average of 18 months
measure: Number of days that P. falciparum infections last in the dry season.
timeFrame: Up to 6 months
measure: Mosquito exposure monitored by monthly CDC-light traps (CDC-LT) and Human landing catches (HLC) mosquito collections
timeFrame: Throughout study, an average of 18 months
measure: Mean fluorescence intensity (MFI) antibody responses to mosquito saliva proteins during high and low transmission season.
timeFrame: Throughout study, an average of 18 months
measure: Number of infections in community surveys that can be linked to a symptomatic or asymptomatic parent infection.
timeFrame: Throughout study, an average of 18 months
measure: Number of human host from mosquito blood meal source.
timeFrame: Up to 12 months
Locations:
city: Basse Santa Su
country: Gambia
facility: Medical research Council Unit The Gambia at LSHTM
Study officials:
affiliation: London School Hygiene and Tropical medicine
name: Chris Drakeley, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MRC Unit The Gambia @ LSHTM
name: Umberto D'Alessandro, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands
name: Teun Bousema, PhD
role: PRINCIPAL_INVESTIGATOR
References: