Research Article: Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme

Date Published: July 17, 2015

Publisher: Public Library of Science

Author(s): Hugo C. Turner, Martin Walker, Sara Lustigman, David W. Taylor, María-Gloria Basáñez, Andrew Fenton.

Abstract: BackgroundCurrently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas.Methodology/Principal FindingsWe used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups.Conclusions/SignificanceAn onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and offering an important additional tool to mitigate the potentially devastating impact of emerging ivermectin resistance.

Partial Text: Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin, which Merck & Co. have committed to donate for as long as needed to eliminate onchocerciasis as a public health problem. Since 2010 there has been a dramatic shift in onchocerciasis control policy in Africa, with programmes changing their aim from elimination of the disease burden to elimination of the infection where feasible. The World Health Organization’s (WHO) Roadmap on Neglected Tropical Diseases [1]—endorsed by the London Declaration on NTDs (LDNTD, 31 January 2012) [2]—set goals for elimination of Onchocerca volvulus infection in selected countries of Africa by 2020. The African Programme for Onchocerciasis Control (APOC) has pledged elimination of onchocerciasis where possible by 2025 [3], and the Bill and Melinda Gates Foundation foresees that global elimination will be reached by 2030 [4]. We have previously indicated, based on mathematical modelling of onchocerciasis transmission and control with EPIONCHO, that the feasibility of eliminating the infection depends primarily on baseline (pre-control) levels of endemicity, patterns of transmission, magnitude of residual transmission between inter-treatment periods, therapeutic coverage and importantly, compliance to treatment, precluding a one-size-fits-all approach to elimination [5,6,7,8]. There is a consensus among the global health community, substantiated by mathematically modelling, that onchocerciasis in Africa will not be eliminated in all endemic foci with annual ivermectin MDA alone [9,10,11], and that novel supportive health intervention technologies, including a vaccine, and/or alternative treatment and control strategies are badly needed [2,12,13].

A key prerequisite to understanding how an onchocerciasis vaccine might mitigate the chances of reinfection from uncontrolled areas or areas with incomplete control is to consider the fraction of blackfly bites that are taken from different age groups by amalgamating the demographic structure of the population and the age- and sex-specific patterns of exposure to blackfly bites. This is illustrated in Fig 7 and demonstrates that the groups of the population protected by the vaccine (those aged less than 20 years) receive collectively most of the bites (because they are more numerous, Fig 2). Comparing this distribution (Fig 7) with the projected age-specific protection against incoming worms (prophylactic efficacy) after 15 year of vaccination (Fig 8), suggests that an onchocerciasis vaccine could markedly decrease the chance of onchocerciasis infection re-spreading to areas where treatment has been stopped (because it protects the age group who receive most bites). Hence, an onchocerciasis vaccine could help to protect the substantial investments already made by donors and stakeholders of ivermectin MDA programmes. However, this result is sensitive to the assumed rate of decay of vaccine protection (Fig 8), reinforcing the emphasis that should be placed in the TPP on achieving a vaccine with a long duration of protection.