Impact of Malaria Mass Drug Administration on Malaria Prevalence in Under 15 Children and Pregnant Women

Noguchi Memorial Institute for Medical Research

Status: Completed

Conditions: Malaria

Treatments: Drug: Artemether-lumefantrine (AL)

Study type: Interventional

Funder types: Other

Identifiers

NCT07358767

NoguchiMIMR 2

Details and patient eligibility

About

This is a clinical trial being done to find better ways to reduce malaria in the community. Malaria is caused by a parasite that is spread by mosquitoes. Some people, especially adults, can carry the malaria parasite without feeling sick, but mosquitoes can still pick up the parasite from them and pass it to others. This makes it hard to stop malaria, particularly among children and pregnant women who are more likely to become ill.

The purpose of this study is to reduce malaria by removing the parasite from as many people in the community as possible, including those who do not have symptoms. By treating everyone, the study aims to reduce the spread of malaria and protect vulnerable groups such as children.

All members of households that agree to take part will be tested for malaria. After testing, everyone will be given malaria medicine, whether or not they feel sick. Participants will be followed up to check for any side effects, such as stomach upset, dizziness, or weakness.

By reducing the amount of malaria parasite in the community, mosquitoes will be less likely to spread malaria from one person to another. If many people participate, malaria illness in the community may decrease, children may stay healthier, and families may spend less money on malaria treatment. The results of this study will help inform future malaria control efforts in similar communities.

Full description

Background Rapid scale-up of malaria control interventions in the past decade led to a reasonable decrease in the burden of malaria. The challenges involved with translating research scenarios into implementation are enormous and needs to be clearly understood. In an era with decreasing funding for the health system, it is important to understand not only the economic impact of MDA in the health of under 15 children but also its effect on the partial immunity of the population. Interventions focused on clearing the parasites in asymptomatic individuals in combination with intensive use of other control measures could pave the way for pre-elimination of malaria in endemic communities, especially in an era when the SAR-var-2 virus is ravaging countries across the world. It is important to generate data on the trends on the population acquired anti-malarial immunity over time following MDA. This information could be very important for national malaria control programmes for decision-making and planning scale-up of malaria MDA, either nationally or regionally.

Several studies in Ghana have demonstrated very high levels of asymptomatic malaria in both under five and school age children who have a higher risk of coming down with clinical malaria or continue to serve as a transmission reservoir. IPT of children in a community in the southern parts of the country reportedly reduced the parasite load by 90 % in two years. It has been demonstrated that IPT using SP impacted the production of protective antibodies against malaria. Immuno-suppression has also been reported from experimental studies of artemisinin-derivatives. In Ghana, malaria incidence during the post-intervention period with SP was increased by 62% in infants who received six monthly artesunate + amodiaquine, but this rebound was not seen in children aged one year or more at the time of drug administration. This rebound effect has been observed where the IPT intervention targeted only children leaving out the adults who could be asymptomatic but transmitting. Though this study targets the entire population, the effect of MDA on malaria prevalence will be evaluated in under 15 children. While there are concerns that eliminating the parasite in an endemic community could lead to a rebound or fatalities should the parasites be reintroduced, malaria passive case detection and management will therefore continue to be through the health facilities in the study areas. A recent study in Mali demonstrated that implementing SMC does not affect acquired immunity in children following four rounds.

In a pilot scale-up study of MTTT in the Pakro subdistrict of Ghana, a coverage of more than 79% and a reduction in asymptomatic malaria prevalence of 24% was achieved, and a reduction of 67% in severe anaemia following 3-rounds of MTTT interventions over 1-year only. These results could be further improved if the sub-microscopic parasitaemia is targeted through malaria MDA.

Aims or Objectives of study

Primary objective The main aim of this study is to determine the impact of implementing malaria MDA on malaria prevalence in under 15 children.

Secondary objectives

1. To determine the prevalence of malaria asymptomatic parasitaemia in populations within the Pakro sub district.
2. To assess the effect of malaria MDA on anaemia in under 15 children.
3. To determine the effect of malaria MDA on febrile patients attending health facilities in intervention arm compared to the control arm.
4. To assess the effect of scaling up malaria MDA on malaria antibodies over time in asymptomatic participants.

Study participants:

Community entry activities to sensitise the chiefs and the general population will be conducted at the beginning of the study through meetings and durbars. Once the community leaders and the population have accepted the project, the households will be numbered and participants in each household will be registered during a household census. All households will be given a unique identification code. Everyone within the household will be assigned a code that links them to a particular household and community. After obtaining consent from the household heads, the children will be enrolled but individual assent and consent will be obtained from the other adolescents and adults in the household. The intervention study will target all the household members. The primary outcome will be based on data from all enrolled participants. The effect of the interventions on secondary outcome 1 will be observed in all children aged 2 months to 14 years randomly. In addition, selected under 15 children will have in addition to the other data, their Hb readings taken to assess the level of anaemia. The effect of the interventions on secondary outcome 2 will be observed in all under 15 children. Furthermore, the effect of the intervention on secondary outcomes 3 and 4 will be observed in all participants. The investigators hypothesize that within the study population, the prevalence of asymptomatic parasitaemia should drop by 90% by the end of the first year and by 95% by the end of the second year. This is estimated based on the findings of Ahorlu and colleagues, 2011. In the same light the investigators expect that anaemia should drop by the same proportion.

Enrollment: 3,300 patients

Sex: All

Ages: 2+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• participant must be aged 2 months and above
• be resident in the communities for the period of the study.
• willingness to participate will be proven by a completed and signed consent or assent form.
• Administrative authorization is obtained from the Ghana Health Service and NMIMR IRB.

Exclusion criteria

• an individual intends to stay less than one year in the study site or
• an individual who would be absent at some time due to schooling in a boarding school
• has a life-threatening illness (excluding malaria).
• Pregnant women will be tested and if positive referred to the Pokrom Health Centre for appropriate management.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

3,300 participants in 2 patient groups

Intervention arm: treated Artemeher Lumefantrine (AL) during MDA, Control arm no intervention

Active Comparator group

Description:

Trained community health workers (CHWs) will conduct door-to-door testing of all participants in intervention arm for malaria parasites using RDTs. This is to determine malaria prevalence. All participants are treated in the intervention arm irrespective of results while only the positive cases will be treated in the control arm. For molecular studies, 200ul (two drops) of blood will be collected on filter paper. Treatment using AL will be conducted following the Ghana National Malaria Treatment Guidelines and followed-up for 4 days (day 1, 2, 3 and 7). Those who receive the treatment will be observed for 30 minutes to ensure that they retain the drug. Those who vomit within this period will have the treatment repeated. Since it is required that patients eat before taking the drug, and household members may not have food when they are tested, some will have to take the medicine later after eating. The research team will pass round to verify that the participants adhering to treatment.

Treatment:

Drug: Artemether-lumefantrine (AL)

Control arm

No Intervention group

Description:

There will be intervention in the control arm. CHWs will will conduct two rounds of screening with RDTs at baseline and at evaluation, and treating positive cases with AL. In both arms, if a participant become febrile at any time, they will be tested and treated if confirmed positive for malaria by CHWs or referred to the health facility for further investigation. All participants will be tested to determine the prevalence at baseline and endline. This is meant to allow for comparison across sites. Hospital data will also be assessed to determine the impact of the interventions on prevalence of symptomatic malaria parasitaemia in the communities.