Lay title

Evaluation of the effectiveness of IVERMECTIN co-formulation vs. ALBENDAZOLE for treatment of worms

Background

Intestinal parasitic worm (STH) are common parasitic infections in Kenya, causing loss of blood and gastrointestinal problems and affecting how a child perfomes at school. The current World Health Organization (WHO) control strategy for worms emphasizes control of sickness cause by worms through mass deworming with albendazole or mebendazole, mainly  pre-school and school-aged children in areas where worms are found in Kenya. However, researchers have raised concerns about the success of these treatment of worms using single drugs as a low and ability of these drugs aganist against whipworms, and the possibilities that mass deworming could lead to the emergence of albendazole failure of the drugs to cure sicknes caused by the worms. Investigating the effectiveness of alternative drugs is important to ensure that these control mass deworming programmes are successful in achieving the target of controlling sickness causes by worms and eventually get rid of worminfection.

What questions are we trying to answer?

We want to find out whether combining albendazole and ivermectin into a single drug will be more effective in treating of whipworm infection. The current drugs (albendazole and mebendazole) that are being used for the treatment of whipworm infections are not efficacious; therefore, many children remain infected. We also wish to find out if there is any resistance that can be identified to current deworming drugs that are being used.

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

The study will take place in public primary schools whose village catchment areas are villages along the shores of the Indian Ocean in Kwale county. Approximately 800 children aged between 5-17 years attending one of the participating primary schools who have informed parental consent will be recruited into the study. Children will be selected to be part of the study based on willingness to be part of the research study and being infected with either hookworm, whipworm or threadworm.

What does the study involve for those who are taking part?

At the beginning of the study, we will take a stool sample from the children to find out whether or not they are infected with worms. If children do not have worms or only have bilharzia, they will not be included in the study. Children who are infected with hookworm or whipworm or both will be recruited into the study. Once recruited, the children will be randomly assigned into one of the three study arms. Children will then be treated according to the treatment arm in which they were assigned. Twenty-one days after treatment, a stool sample will be collected to check for infection clearance. Study participants will be monitored by study doctors for 3h after treatment for adverse events that may have occurred as a result of treatment. Three and seven days after treatment, children will be revisited at the school premises for adverse event monitoring. In 100 childeren included in the first part of the study blood from a finger prick less than 1ml will be taken to conuct pharmacokinetics assessment at 4, 8, 24, 52 and 78 hours post treatment.

What are the risks and benefits involved in taking part?

The drugs are known to show excellent safety profile except for those patients harbouring Loa loa infection(1). In recent studies, descriptions of little visual disturbance were observed. These events were reported to be mild, transient, and of short duration (a few minutes to a few hours). For this reason, in this study, subjects will be observed closely for any immediate risks after study drug administration. We do not think there will be any long-term effects on the participants. The use a combination of albendazole and ivermectin in the proposed combination therapy against STH could offer a solution to several disadvantages in the current strategy in terms of curing of whipworm infection. Participants may experience minor discomfort during the collection of finger-prick blood samples.

How will the study benefit society?

The results from this study will offer insight for the effectiveness of a new combination of albendazole and ivermectin with great potential of improving the control of helminth worldwide, with emphasis on whipworms that are currently difficult to treat. Further this results, may increases the possibility of elimination of helminth with the possibility of a more effective drug. Millions of Africans living in areas where whipworm occurs may benefit.

When does the study start and finish?

It is estimated that the study will take 18 months from recruitment (January 2021) until completion of data analyses (September 2022).

The current World Health Organization (WHO) control strategy for Soil-Transmitted Helminths (STH) emphasizes morbidity control through mass drug administration with albendazole or mebendazole, mainly targeting pre-school and school-aged children in endemic areas. Increasing concerns have been raised about the success of these monotherapy strategies: 1) whilst albendazole is still efficacious against Ascaris lumbricoides and hookworm, a low and decreasing efficacy against Trichuris trichiura is observed, and none of these strategies is effective against S. stercoralis; 2) the use of widespread monotherapy could lead to the emergence of albendazole resistance. Modelling studies predict a huge impact on years lived with disability and economic productivity, if these strategies remain unchanged. Ivermectin has shown an enhanced activity against T. trichiura when combined with albendazole, and is considered the drug of choice against strongyloidiasis and other parasitic infections. Adding ivermectin to albendazole would increase efficacy of the interventions, and decrease the possibility of emergence of resistance, as recently suggested by WHO and the Bill and Melinda Gates Foundation reports.

The main goal of this project is to develop and test the safety and efficacy of a fixed-dose co-formulation of ivermectin and albendazole against STHs, as a single dose and a three-dose regimen, compared to a single dose of albendazole in a phase III clinical trial. The project will be conducted in schools in Kwale county along the shoreline of the Indian Ocean that has been shown to have high prevalence of Trichiris trichiura. The study population will be school aged children 5-15 years.

The project will include capacity building and networking activities. Besides microscopy-based procedures, parasite DNA detecting techniques (PCR) will be used and validated as markers of treatment response. Modelling studies will evaluate the potential impact on transmission and economic benefits of the new treatment regimen. The scientific results will be presented to the scientific community, local governments and other implementation actors and stakeholders. Previous collaborations of members of this consortium developed and tested the safety of a fixed high dose of ivermectin, as a first step towards the fixed- dose combination with albendazole. This consortium integrates complementary expertise in drug development, manufacture and expertise in drug development, manufacture and regulatory processes, expertise in parasitology, veterinary, epidemiology and public health.