Ivermectin-artemisinin Combination Therapy for Eradication of Malaria

Overview

Malaria remains a leading cause of morbidity and mortality globally. Uganda has the 3rd highest global burden of malaria cases (5%) and the 7th highest level of deaths (3%), accounting for over 10,500 deaths annually. Uganda also has the highest proportion of malaria cases in East and Southern Africa (23.7%). Even with the current prevention strategies including use of impregnated mosquito nets, in 2017, malaria still accounted for 27-34 % of outpatient visits, 19-30 % of hospital admissions, up to 20% of all hospital deaths nationally. A significant percentage of deaths occur at home and are not reported by the facility-based Health Management Information System (HMIS). 27.2% of inpatient deaths among children under five years of age are due to malaria. The transmission of Plasmodium from humans to mosquitoes depends on the presence of mature gametocytes transmission stages. The current first-line treatment for uncomplicated falciparum malaria is artemether lumefantrine, an artemisinin combination therapy (ACT) which rapidly clears asexual parasites and developing gametocytes but leaves mature P. falciparum gametocytes largely unaffected, thus a proportion of patients may transmit malaria after successful ACT treatment and there is an urgent need to prevent this malaria transmission.

Malaria remains a leading cause of morbidity and mortality globally, responsible for about one million deaths annually. 90% of these deaths occur in Africa, majority (90%) of whom are children under 5 years old, thus the focus of a global eradication campaign announced in 2007. Uganda has the 3rd highest global burden of malaria cases (5%) and the 7th highest level of deaths (3%), accounting for over 10,500 deaths annually. Uganda also has the highest proportion of malaria cases in East and Southern Africa (23.7%). Even with the current prevention strategies including use of impregnated mosquito nets, in 2017, malaria still accounted for 27-34 % of outpatient visits, 19-30 % of hospital admissions, up to 20% of all hospital deaths nationally. A significant percentage of deaths occur at home and are not reported by the facility-based Health Management Information System (HMIS). 27.2% of inpatient deaths among children under five years of age are due to malaria. Malaria has an indirect impact on the economy and development in general with socio-economic impact like out-of-pocket expenditure for consultation fees, drugs, transport to distant health facilities, such costs estimated to be as high as USD 3.88 per person per month (26 per household) or 3% of their annual income. Household expenditure for malaria treatment is also a high burden to the Ugandan population, consuming a larger proportion of the incomes in the poorest households. Additionally, malaria has a significant negative impact on the economy of Uganda due to loss of workdays because of sickness, decreased productivity, and decreased school attendance. Workers suffering from malaria may not be able to work for an estimated 5-20 days per episode and given that many people are at times infected multiple times a year, this has substantial financial consequences to families. Industries and agriculture also suffer due to loss of person-hours and decreased worker productivity and investors are usually wary of investing in such countries where malaria rates are high, leading to a loss in investment opportunities. Further, severe malaria impairs children's learning and cognitive ability by as much as 60%, consequently affecting the performance of Uganda's education programs. The transmission of Plasmodium from humans to mosquitoes depends on the presence of mature gametocytes transmission stages. The current first-line treatment for uncomplicated falciparum malaria is artemether lumefantrine, an artemisinin combination therapy (ACT) which rapidly clears asexual parasites and developing gametocytes but leaves mature P. falciparum gametocytes largely unaffected, thus a proportion of patients may transmit malaria after successful ACT treatment and there is an urgent need to prevent this malaria transmission. The current malaria prevention strategies in Uganda focus on the "keep healthy by avoiding malaria" phenomenon without the involvement of the host. Although key in malaria prevention, chemotherapeutic malaria preventive strategies are rarely used in Uganda since the currently available malaria prophylactic agents like mefloquine are only recommended for persons with short stay in malaria endemic settings. In short, to date there are limited malaria chemoprophylaxis options for resident Ugandans generally limiting the practice of malaria prevention.