LAY SUMMARY

Lay Title

Evaluation of ivermectin mass drug treatment to reduce malaria transmission in Coastal Kenya.

What is the problem/background?

Malaria is transmitted by mosquitoes. Malaria has been reduced in Kenya using bed-nets and spraying of insecticides that kill mosquitoes, but malaria still exists in many places including in Kwale. Mosquitoes can adapt, become resistant to insecticides, and change their behavior to bite at times when people are not under their bed-net as well as on animals. We need to find a way to fight mosquitoes in addition to the bed nets, that can control mosquitoes that bite outdoors and when people are not under their nets. Ivermectin is a drug commonly used as to treat worms, however if a mosquito bites a human or animal who has been treated with ivermectin it will not survive for a long time and may not be able to spread malaria. Administering ivermectin to as many people as possible at the same time in a community, might be a new way to control the mosquitoes and needs to be tested. We also want to know if treating humans and cattle with ivermectin works better than just treating humans, this is because mosquitoes also like to feed on cattle.

What questions are we trying to answer?

The study is designed to answer the following questions: is malaria transmission reduced by distributing ivermectin to all human, or humans and cattle,  once a month for three months during the rainy season? Is it safe? The study will be divided in geographic areas called clusters and all residents of each cluster will be allocated to three possible treatments:

1) Ivermectin 400mcg/Kg will be given to all eligible humans whilst all cattle in these clusters will be left untreated;

2) Ivermectin 400mcg/Kg will be given to all eligible humans and ivermectin 200mcg/Kg will be given to all cattle in these clusters;

3) Albendazole 400mg (control) will be given to all eligible humans whilst cattle will be left untreated.

Where is the study taking place, how many people does it involve and how are they selected?

The study will take place in the sub-counties of Msambweni and Lungalunga in Kwale county, Kenya. All residents of the study areas will be eligible for inclusion unless they weigh less than 15kg, are pregnant or are taking certain drugs. In total, approximately 45,000 participants will be recruited with support from the Kwale county community health services platform. The study area will be divided into geographic units called clusters, residents of each cluster will be visited monthly for 3 months during the long rains to receive the treatment and will be followed up for any side effects to assess if the drug is safe (safety). In each cluster we will recruit a group of 25-35 children 5-15 years old. These children will be followed up to assess whether the drug has an impact on malaria (efficacy group). The children will be followed-up monthly through household visits for six months. Every month a study member will take a drop of blood by finger prick for a malaria rapid test and record whether it was negative or positive, if the child is found to have malaria the study team will provide treatment. One month after the last round of treatment, a random sample of people of all-ages living in the study area will be selected to collect a drop of blood on filter paper for determining the proportion of people who have malaria in each group (cross sectional study). In addition, we believe ivermectin may also help control other parasites, for this reason we will randomly select a smaller group of participants (1,044) and examine them for skin lesions caused by other parasites (neglected tropical diseases -NTDs-). Because the effect of ivermectin depends on its blood concentrations, we will ask 160 randomly selected people 18 years or older to provide drops of blood on filter paper which we will analyze in the laboratory for amount of drug. Participants experiencing side-effects of ivermectin such as dizziness may be asked to give a small blood sample to look for two specific genetic variations that can influence ivermectin concentrations in the body.

What does the study involve for those who are in it?

Participants will be asked to take ivermectin or albendazole once every month for three months. They will also be requested to answer a few questions about any possible adverse events caused by the drug, or any symptoms experienced in between visits, as well as their healthcare seeking behavior, during four months in total. Women who participate in the treatment group and become pregnant in between visits, will not receive treatment again, but their pregnancy will be followed monthly up to term. The children recruited to the efficacy group will be tested for malaria by finger prick monthly for 6 months. Those who are positive for malaria will receive antimalarial treatment according to national guidelines. The participants in the NTD sub-sample will be examined for skin lesions. The participants in the cross-sectional study will be tested for malaria by finger prick and those who are positive will be treated with anti-malarials. All blood sampling will be done by fingerprick. The amount of blood taken with finger pricks is very small and will be less than a spoonful for the entire study.

What are the benefits and risks/costs of the study for those involved? 

Both ivermectin and albendazole are dewormers that are regularly used in deworming campaigns done in Kenya. The ivermectin dose chosen for this clinical trial is higher than what is usually used in Kenya. However, it is approved in a few countries in the European Union. Ivermectin will be used more often than usual because people will be treated once every month and this could potentially lead to build up of the drug in the body, however there is evidence that this is unlikely to occur. Ivermectin should not be taken during pregnancy, for this reason we will ask all women who are old enough to be pregnant (13+) if they agree to a pregnancy test. The test will be a urine test done by the woman in private, the results will not be shared with anyone else. If a woman becomes pregnant in between treatments, they will not be given any more drug and their pregnancy will be followed up to term. There is also risk that drugs that people take regularly can interact with ivermectin, we will ask participants whether they take any medication regularly and exclude them if appropriate.

Other risks to be considered are those arising from taking blood samples (i.e.; small risk of infection, temporary pain or bruising from finger prick). Additionally, there could be a social risk derived from women of child bearing age being asked and tested for pregnancy.

The study will involve no cost for the participants.

How will the study benefit society? 

This study will benefit society by finding out if mass drug administration of ivermectin can be used as a new way to decrease malaria in addition to bed nets.

When does the study start and finish?

The first round of MDA will occur during the long rains season of 2023, participants will be recruited and consented a few days or weeks in advance. Participation of the safety group will end one month after the last dose, whereas the efficacy group will continue up to 6 months after the first dose. For women becoming pregnant during the study, participation will continue for a maximum of 9 months after the third round of treatment. Participants selected to be part of the NTD sub-study will be examined during the safety and efficacy household visits. People in the cross-sectional study will only be part of the study for one household visit, one month after the last dose of study drug. Those participating in the smaller study about ivermectin concentrations will need to be available for a period of five days, the first of which will require a day at a hospital site.