P. Falciparum Infection Dynamics and Transmission to Inform Elimination
Palabras clave
Abstracto
Descripción
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.
fechas
| Verificado por última vez: | 07/31/2019 |
| Primero enviado: | 07/28/2019 |
| Inscripción estimada enviada: | 08/07/2019 |
| Publicado por primera vez: | 08/12/2019 |
| Última actualización enviada: | 08/07/2019 |
| Última actualización publicada: | 08/12/2019 |
| Fecha de inicio real del estudio: | 08/14/2019 |
| Fecha estimada de finalización primaria: | 01/29/2021 |
| Fecha estimada de finalización del estudio: | 03/29/2021 |
Condición o enfermedad
Intervención / tratamiento
Other: Community Case Management
Other: CCM plus weekly fever screening and treatment
Other: CCM plus MSAT
Other: CCM plus dry season MDA
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| No Intervention: CCM:Standard of Care Community Case Management (CCM), with passively monitored malaria incidence by community health workers using standard RDTs and artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL) according to national guidelines. | |
| Experimental: CCM plus weekly fever screening and treatment CCM plus active case detection (ACD) by fever screening and treatment if positive. Trained VHW recruited for this study will carry out weekly visits of all residents and screen for fever using research-grade thermometers. A standard RDT will be performed in all individuals with a body temperature ≥37.5°C or with reported fever in the last 24 hours. RDT positive individuals will be treated with AL according to national guidelines. | Other: CCM plus weekly fever screening and treatment Consists of weekly visits by trained VHW who will screen for fever by taking the axillary temperature. If the body temperature is ≥37.5°C, a standard RDT will be performed and, if positive, the individual will be treated with AL, according to national guidelines. |
| Experimental: CCM plus MSAT CCM plus monthly screening for malaria infection and treatment of positive individuals, regardless of symptoms. Screening will be performed by research staff and timed to ensure a gap of 25-35 days between screening rounds; Positive individuals will be treated with AL, according to national guidelines. | Other: CCM plus MSAT CCM plus monthly screening of the whole population with high sensitive RDT (HS-RDT); positive individuals will be treated with AL regardless of symptoms (MSAT). |
| Experimental: CCM plus dry season MDA CCM plus plus 3 monthly rounds of MDA with a long-acting ACT (dihydroartemisinin-piperaquine, DP) starting in the dry season (April, May, June) (tablets of 320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet. Administration of a full course of DP will be done as per manufacturer's guidelines once daily for 3 days and according to body weight). | Other: CCM plus dry season MDA CCM plus 3 monthly rounds of MDA with dihydroartemisinin-piperaquine (DP) starting during the dry season, before the malaria transmission season starts. |
Criterio de elegibilidad
| Edades elegibles para estudiar | 6 Months A 6 Months |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | 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 30mL of blood (children <5 years of age), 37mL of blood (children <10 years of age) or 52mL 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 QTc interval (only for Arm with MDA-DP treatment). |
Salir
Medidas de resultado primarias
1. Parasite prevalence by molecular detection at the end of study (cross-sectional survey). [16 weeks]
2. Parasite density by molecular detection at the end of study (cross-sectional survey). [16 weeks]
Medidas de resultado secundarias
1. Gametocyte prevalence by molecular methods at the end of study (cross-sectional survey). [16 weeks]
2. Gametocyte density by molecular methods at the end of study (cross-sectional survey). [16 weeks]
3. Gametocyte prevalence of male and female gametocytes by molecular methods among P. falciparum infections at all study visits. [Throughout study, an average of 18 months]
4. Gametocyte density of male and female gametocytes by molecular methods among P. falciparum infections at all study visits. [Throughout study, an average of 18 months]
5. Incidence of malaria infections [Throughout study, an average of 18 months]
6. Infectivity of P. falciparum infections to mosquitoes [Throughout study, an average of 18 months]
Otras medidas de resultado
1. The detectability of infections by highly-sensitive rapid diagnostic tests related to histidine rich protein-2 (HRP2) concentrations. [Throughout study, an average of 18 months]
2. The detectability of infections by highly-sensitive rapid diagnostic tests related to duration of infection. [Throughout study, an average of 18 months]
3. The detectability of infections by rapid diagnostic tests related to duration of infection. [Throughout study, an average of 18 months]
4. The detectability of infections by highly-sensitive rapid diagnostic tests related to parasite density by molecular diagnostics. [Throughout study, an average of 18 months]
5. The detectability of infections by rapid diagnostic tests related to parasite density by molecular diagnostics. [Throughout study, an average of 18 months]
6. The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte density. [Throughout study, an average of 18 months]
7. The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte sex-ratio. [Throughout study, an average of 18 months]
8. The effect of infection characteristics (clonal parasite infection) on the transmissibility of infections to mosquitoes. [Throughout study, an average of 18 months]
9. Gametocyte sex-ratio on the transmissibility of infections to mosquitoes. [Throughout study, an average of 18 months]
10. The impact of human haemoglobinopathies on the transmissibility of infections to mosquitoes. [Throughout study, an average of 18 months]
11. Mean fluorescence intensity (MFI) to inflammatory markers and naturally acquired antibody responses to gametocyte antigens on the transmissibility of infections to mosquitoes. [Throughout study, an average of 18 months]
12. Relationship between total parasite density (parasite/µL) and gametocyte density (gametocytes/µL) [Throughout study, an average of 18 months]
13. Malaria transmission potential based on measured gametocyte densities (gametocytes/µL). [Throughout study, an average of 18 months]
14. Number of acquired parasite clones based on genotyping. [Throughout study, an average of 18 months]
15. Number of days that P. falciparum infections last in the dry season. [Up to 6 months]
16. Mosquito exposure monitored by monthly CDC-LT and HLC mosquito collections [Throughout study, an average of 18 months]
17. Mean fluorescence intensity (MFI) antibody responses to mosquito saliva proteins during high and low transmission season. [Throughout study, an average of 18 months]
18. Number of infections in community surveys that can be linked to a symptomatic or asymptomatic parent infection. [Throughout study, an average of 18 months]
19. Number of human host from mosquito blood meal source. [Up to 12 months]
