Human leishmaniasis vaccines: Use cases, target population and potential global demand.

The development of vaccines against one or all forms of human leishmaniasis remains hampered by a paucity of investment, at least in part resulting from the lack of well-evidenced and agreed estimates of vaccine demand. Starting from the definition of 4 main use cases (prevention of visceral leishmaniasis, prevention of cutaneous leishmaniasis, prevention of post-kala-azar dermal leishmaniasis and treatment of post-kala-azar dermal leishmaniasis), we have estimated the size of each target population, focusing on those endemic countries where incidence levels are sufficiently high to justify decisions to adopt a vaccine. We assumed a dual vaccine delivery strategy, including a wide age-range catch-up campaign before the start of routine immunisation. Vaccine characteristics and delivery parameters reflective of a target product profile and the likely duration of the clinical development effort were considered in forecasting the demand for each of the four indications. Over a period of 10 years, this demand is forecasted to range from 300-830 million doses for a vaccine preventing visceral leishmaniasis and 557-1400 million doses for a vaccine preventing cutaneous leishmaniasis under the different scenarios we simulated. In a scenario with an effective prophylactic visceral leishmaniasis vaccine, demand for use to prevent or treat post-kala-azar dermal leishmaniasis would be more limited (over the 10 years ~160,000 doses for prevention and ~7,000 doses for treatment). Demand would rise to exceed 330,000 doses, however, in the absence of an effective vaccine for visceral leishmaniasis. Because of the sizeable demand and potential for public health impact, a single-indication prophylactic vaccine for visceral or cutaneous leishmaniasis, and even more so a cross-protective prophylactic vaccine could attract the interest of commercial developers. Continuous refinement of these first-of-their kind estimates and confirmation of country willingness and ability to pay will be paramount to inform the decisions of policy makers and developers in relation to a leishmaniasis vaccine. Positive decisions can provide a much-needed contribution towards the achievement of global leishmaniasis control.

The prevention of canine leishmaniasis and its impact on public health.

Canine leishmaniasis (CanL) caused by Leishmania infantum is a vector-borne disease of great veterinary and medical significance. Prevention of CanL requires a combined approach including measures focused on dogs and the environment where the vectors perpetuate. Over past decades, considerable effort has been put towards developing novel and cost-effective strategies against CanL. Vaccination is considered among the most promising tools for controlling CanL, and synthetic pyrethroids are useful and cost-effective in reducing risk of L. infantum infection in dogs. The effectiveness of the use of vaccines plus repellents in preventing L. infantum infection and subsequent disease development should be assessed by means of large-scale, randomized controlled field trials because this combined strategy may become the next frontier in the control of CanL.

The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas.

Cutaneous leishmaniasis (CL) and its associated complications, including mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL) have emerged as important neglected tropical diseases in Latin America, especially in areas associated with human migration, conflict, and recent deforestation. Because of the limitations of current chemotherapeutic approaches to CL, MCL, and DCL, several prototype vaccines are in different states of product and clinical development. We constructed and utilized a Markov decision analytic computer model to evaluate the potential economic value of a preventative CL vaccine in seven countries in Latin America: Bolivia, Brazil, Colombia, Ecuador, Mexico, Peru, and Venezuela. The results indicated that even a vaccine with a relatively short duration of protection and modest efficacy could be recommended for use in targeted locations, as it could prevent a substantial number of cases at low-cost and potentially even result in cost savings. If the population in the seven countries were vaccinated using a vaccine that provides at least 10 years of protection, an estimated 41,000-144,784 CL cases could be averted, each at a cost less than the cost of current recommended treatments. Further, even a vaccine providing as little as five years duration of protection with as little as 50% efficacy remains cost-effective compared with chemotherapy; additional scenarios resembling epidemic settings such as the one that occurred in Chaparral, Colombia in 2004 demonstrate important economic benefits.

Visceral leishmaniasis: immunology and prospects for a vaccine.

Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease.

Leishmaniasis vaccines: past, present and future.

No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.