Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting

Abstract

Background Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. Methods We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Results Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤$790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤$444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) than annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0%, nearly eliminated hookworm infection in children. Conclusion Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally.

Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections

“…In the case of lymphatic filariasis and onchocerciasis, this approach may lead to the elimination of these diseases as a public health program in the coming decade, with additional or collateral benefits for additional neglected infections, including scabies [11]. However, for hookworm infection and schistosomiasis, there is an expectation that additional control tools, such as vaccines, will be required in order to effect elimination efforts [12,13]. Similarly, for malaria, tremendous gains have been achieved through the administration of antimalarial drugs and insecticide-treated bed nets, but a vaccine will still be required to go the last mile for this ancient scourge.…”

“Running the Gauntlet”: Formidable challenges in advancing neglected tropical diseases vaccines from development through licensure, and a “Call to Action”

“…[25][26][27] Additional efforts have modeled the cost-effectiveness of NTD vaccines, 19,20 or vaccines linked to chemotherapy. 28,29 For example, a modeling study to evaluate a hookworm vaccine delivered with preventive chemotherapy has the potential for positive societal benefits, while at the same time be cost-effective. 29 Therefore, more cost-economic studies are needed to investigate the mechanisms by which NTD or "antipoverty" vaccines could prevent debilitating disease and improve long-term economic outcomes.…”

“…28,29 For example, a modeling study to evaluate a hookworm vaccine delivered with preventive chemotherapy has the potential for positive societal benefits, while at the same time be cost-effective. 29 Therefore, more cost-economic studies are needed to investigate the mechanisms by which NTD or "antipoverty" vaccines could prevent debilitating disease and improve long-term economic outcomes. [23][24][25] The framework of Texas Children's CVD Similar to what was presented by Denee, et al in 2012, 26 for the past two decades, Texas Children's CVD has adapted and refined an operational framework with guiding principles ( Table 2) and objectives (Box 2) that allows to measure indicators of success as well as recognize, early on, the challenges of each vaccine development program:…”

“…Through health economic modeling, the return on investments for several NTD vaccines including vaccines for hookworm infection, Chagas disease, and leishmaniasis clearly point to major economic returns in terms of improved productivity, a more robust workforce, reduced hospitalization, and other social goods that translate into overall national development. 9,28 Additional modeling studies have shown how NTD vaccines can accelerate the control and elimination of these povertypromoting diseases, 28,29 especially for hookworm infection and schistosomiasis. However, while modeling and other evidence support the economic dominance of NTD and antipoverty vaccines, these aspects by themselves have not yet been sufficient to promote substantial and timely global investments.…”

The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates

“…Therefore, development of a vaccine has emerged as a practical and feasible alternative technology to control hookworm infection or complement anthelmintic drug treatment [ 1 , 8 ]. A human hookworm vaccine is considered both cost-effective and cost-saving relative to mass drug administration [ 9 ].…”