Effectiveness, Feasibility and Acceptability of Seasonal Malaria Chemoprevention in Aweil South County in South Sudan

Effectiveness, Feasibility and Acceptability of Seasonal Malaria Chemoprevention in Aweil South County in Northern Bahr Eel Ghazal, South Sudan: A Type 2 Hybrid Effectiveness-implementation Study Using a Convergent Mixed-methods Approach

This study aims to explore whether SMC is an effective intervention in the context of Northen Bahr el Gazal state, South Sudan. It also aims to assess the protective efficacy of the antimalarials used in SMC in the target population and investigate levels of parasite resistance in the study counties. If successful, this trial should provide the evidence for SMC to be included in malaria programming and policy in South Sudan.

A Type II hybrid effectiveness-implementation study design will be used to evaluate the effects of a clinical intervention on relevant outcomes whilst collecting information on implementation. It is designed to determine feasibility and effectiveness of an innovative intervention, as well as the protective efficacy of the antimalarial drugs used. The study consists of five components: 1) A series of cross-sectional surveys establishing confirmed malaria cases in children; 2) A prospective cohort study to determine the protective efficacy of SPAQ (if SPAQ provides 28 days of protection from infection) and whether drug concentrations and/or resistance influence the duration of protection; 3) A resistance markers study in children 3-59 months in the research county; 4) Modelling the protective effect of SPAQ in South Sudan to determine where SMC could be a suitable malaria prevention strategy in other areas of the country, and 5) A process evaluation to understand feasibility and acceptability of the SMC intervention in South Sudan.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: Sulfadoxine pyrimethamine; Drug: Amodiaquine

Detailed Description

This is an implementation research study, using a Type II hybrid effectiveness-implementation study design, to evaluate the effects of a clinical intervention on relevant outcomes whilst collecting information on implementation.

The study uses pragmatic implementation research with the objective of contributing to the development of practical recommendations for health policy, practice and potential scale up. It is designed as an implementation study to determine effectiveness and protective efficacy to gather evidence of its potential impact on health outcomes. Five monthly cycles of SMC will be implemented between June and October 2022 in one county, Aweil South, in Northern Bahr el Gazal state.

The study will comprise the following six components :

1. Two cross-sectional surveys at the height of the malaria season to explore impact on malaria incidence
2. End-of-round survey
3. Prospective protective efficacy cohort study to determine if SPAQ provides 28 days of protection from infection and whether drug concentrations and/or resistance influence the duration of protection
4. Resistance markers study in children 3-59 months in the two research counties plus the two standard intervention counties to measure changes in resistance marker prevalence over time (pre and post within the same year and between years)

• Study Type: Interventional
• Enrollment (Estimated): 3575
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Sudan
  • Northern Bahr El Gazal
    • Aweil, Northern Bahr El Gazal, South Sudan
      • Aweil South

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 4 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Being resident in the project area
• Afebrile with no other malaria associated symptoms in the past 48 hours or at time of recruitment
• Consent to participate in the study obtained
• Can comply with 3 day DOT of standard SPAQ regimen (day 0-2)
• Willingness and ability of the childs guardians to comply with the study protocol for the duration of the study including all dry blood spot and slide collections

Exclusion Criteria:

• Symptoms of malaria (tympanic fever ≥ 37.5 °C or history of fever in past 48 hours)
• Known allergy to medicine provided
• Receiving a sulfa-based medication for treatment or prophylaxis, including co-trimoxazole (trimethoprim-sulfamethoxazole).
• Individuals receiving azithromycin due to the antimalarial activity of azithromycin.
• Severe malnutrition according to WHO guidelines
• Recruited in cross sectional surveys or any other SMC studies.
• Children with HIV
• Previous treatment with Amodiaquine in the past 28 days (treatment with ASAQ or SPAQ)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ); Children aged 3-59 months will receive SPAQ in the intervention arm	Drug: Sulfadoxine pyrimethamine; Sulphadoxine is a slowly eliminated sulphonamide. It is used in a fixed dose combination of 20 parts sulphadoxine with 1 part pyrimethamine given orally or intramuscularly. The medicine is no longer recommended for the treatment of malaria. However, it is being used for Intermittent Preventive Treatment during pregnancy (IPTp) and as a co-packaged combination with amodiaquine for seasonal malaria chemoprevention. Sulphadoxine is readily absorbed from the GIT. It is widely distributed in body tissues and fluids and crosses the placenta into foetal circulation. It is also readily detectable in breast milk. It is excreted predominantly as the unchanged drug.; Other Names: SP; Drug: Amodiaquine; Amodiaquine is a Mannich base 4 amino-quinoline that interferes with parasite haem detoxification. It is more effective than chloroquine in both chloroquine sensitive and resistant P. falciparum infections. However, there is cross-resistance between chloroquine and amodiaquine. It is readily absorbed in the GIT and rapidly converted in the liver to the active metabolite, desethylamodiaquine. Desethylamodiaquine is responsible for all the antimalarial effect.; Other Names: AQ
No Intervention: Control; Children aged 3-59 months will not receive SPAQ in the control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malaria incidence in study population in intervention county and eligible children in one control county	Number of malaria cases in the intervention population and eligible children in one control county over the study period as reported through care givers in cross-sectional surveys at baseline, mid-intervention and endline	Five months
Chemoprevention failure as defined by positive parasites in malaria slides after day 7 or positive qPCR in dried blood spot (DBS) on day 28	Malaria slides and dry blood spots (DBS) taken at days 0,7, 28 will be analysed with qPCR methodology to detect low level submicroscopic parasitemia in children treated with SPAQ	One month
Prevalence of antimalarial resistance markers (dhfr, dhps, Pfcrt, pfmdr1) among chemoprevention failures as defined in outcome 2	All Dried blood spots (DBS) will be analysed for malaria mutation genotypes (dhfr, dhps, Pfcrt, pfmdr1) on baseline and endline and additionally on day 7, day 28, or if participant slide is positive for parasites on day 7 or an infection is reported through care givers in cross-sectional survey.	One month
Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1)	Drug concentrations will be analyzed for all samples on baseline, day 7 and day 28 and will be linked to chemoprevention failure cases as defined in outcome 2 or a malaria infection is reported through care givers in cross sectional survey.	One month

Collaborators and Investigators

• Sponsor: Malaria Consortium
• Investigators: Principal Investigator: Ahmed Ismail Julla, Ministry of Health, South Sudan

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: seasonal-malaria-chemoprevention
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine
• Other Study ID Numbers: SMCSSPHASE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As this data is sensitive we propose not to share it.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No