New supportive health intervention technologies, including a vaccine, will be required to achieve onchocerciasis (river blindness) elimination targets. The Onchocerciasis Vaccine for Africa (TOVA) Initiative brings together an established African and European consortium with USA laboratories in a new partnership to develop and test an onchocerciasis vaccine for Africa.
From control to elimination through mass drug administration
The London Declaration on Neglected Tropical Diseases of January 2012 called for sustained efforts to expand and extend drug access programmes to ensure the necessary supply of drugs and other interventions to help control human onchocerciasis (river blindness). The African Programme for Onchocerciasis Control (APOC) closed in 2016 and its work subsumed by the Expanded Special Project for the Elimination of Neglected Tropical Diseases in Africa (ESPEN) with a new aim of eliminating Onchocerca volvulus, the causative agent of onchocerciasis, by 2025.
APOC’s work was predicated on sole use of mass drug administration (MDA) of ivermectin (MectizanTM). Moving from control to elimination using MDA of ivermectin alone will be a considerable challenge that may not be sufficient to achieve onchocerciasis elimination.
A known deficiency of MDA programming is the fact that ivermectin cannot be used in areas where onchocerciasis and loiasis are co-endemic due to the risk of severe adverse reactions following drug treatment. It is estimated that 12 million people live in such high risk areas in central Africa and are potentially affected by this contraindication. In these areas, communities often do not receive supportive treatment; onchocerciasis transmission rates remain high; and, reintroduction of the infection to neighbouring communities from which the disease has been eliminated is an ongoing threat.
Additionally, the potential widespread emergence of drug-resistant O volvulus poses a threat to the long-term effectiveness of using ivermectin alone in all areas. In some foci, microfilariae are reappearing in the skin following ivermectin treatment at a faster rate than anticipated, and this may be indicative of development of drug resistance.
Successful elimination of onchocerciasis will ultimately require irreversible reductions in O volvulus microfilariae production by 30-35% following each annual round of ivermectin treatment. However, there is great uncertainty around such estimates. Disease modelling studies suggest that, depending on compliance and levels of parasite transmission, it may not be possible to achieve onchocerciasis elimination even after 50 years of annual ivermectin treatments, thereby necessitating the adoption of biannual treatments. This would place additional logistical and financial challenges on MDA programmes as well as potentially increasing the rate of emergence of drug resistance. These models recognize the fact that ivermectin does not kill the (longlived) adult worms and, in areas of high transmission, microfilariae reappear in the skin during the inter-treatment period.
Development of new tools (such as drugs, diagnostics and vaccines) will be required to ensure onchocerciasis elimination and remove the risk of reintroduction of the infection to areas where elimination may have been achieved. Such new tools would potentiate or enhance the efficiency of ivermectin treatments and address the identified deficiencies of the current MDA programming.
The rationale for the feasibility of vaccination against onchocerciasis (and other filarial infections) is founded on evidence from both humans and animal models for the development of protective immunity (https://doi.org/10.1111/j.1365-3024.2011.01350.x; https://doi.org/10.1586/14760584.2015.1059281; https://doi.org/10.1016/j.pt.2017.08.011).
Mathematical modelling has demonstrated that a vaccine could provide a ring-fence to protect areas from re-introduction of infection following successful control (https://doi.org/10.1371/journal.pntd.0003938).
In addition, the use of an onchocerciasis vaccine would mitigate the consequences of a potential spread of ivermectin-resistant O volvulus.
Children: the neglected hosts
Children below 5 years are excluded from ivermectin treatment and this leaves a significant proportion of the population exposed to infection. For example, in Cameroon , 16% of the population are under 5 years (United Nations, http://esa.un.org/unpd/wpp/index.htm). Similar age profiles are found throughout filarial endemic regions of Africa and in populations that are expected to double over the next 25 years (https://www.populationpyramid.net/sub-saharan-africa/2050.htm). Pre-school children comprise a large reservoir of microfilariae that can contribute to transmission.