The potential impact of human visceral leishmaniasis vaccines on population incidence

Rutte, Epke A. Le; Coffeng, Luc E.; Malvolti, Stefano; Kaye, Paul M.; Vlas, Sake J. de

doi:10.1371/journal.pntd.0008468

“…Secondly, assumptions concerning the probability of country vaccine introduction are subject to a high degree of uncertainty given that vaccines will likely not be available for another decade. Thirdly, the estimate of the impact of the use of vaccines in the target populations is based on a set of assumptions while awaiting the outcomes of vaccine trials Work done by Erasmus MC (University Medical Center, Rotterdam) provides information on the potential impact of various VL vaccines on VL incidence in an Indian setting [44], but not elsewhere. Whilst our modelling assumptions include transmission by asymptomatic cases of VL, a recent study from India suggests that this may be more limited than previously thought [58] .…”

Section: Discussionmentioning

confidence: 99%

“…In a similar fashion, we assumed that a CL prophylactic vaccine, while protecting individuals, will have less impact on transmission given the zoonotic nature of this disease, hence immunization will not be stopped in any CL at-risk area. Finally, the impact of a VL prophylactic vaccine on VL incidence and thus, indirectly, also on the size of the target population for the prevention of PKDL was estimated referring to recent disease transmission modelling work for India, where anthroponotic transmission was assumed [44] (29). In that model (under the assumption that asymptomatic individuals also contribute to VL transmission), the reduction in the number of cases following prophylactic vaccination with a 50% efficacious vaccine covering 100% of the population was estimated to be 30%, 50% and 62% in years 1, 2 and 3 following the introduction of the vaccine [44].…”

Section: Impact Of Vaccine Introduction On Target Populations the Introduction Of A Leishmaniasismentioning

confidence: 99%

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

Malvolti¹,

Malhame²,

Mantel³

et al. 2021

Preprint

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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 310-830 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.Author SummaryThe leishmaniases are potentially vaccine-preventable diseases of global importance, yet no vaccines for human use have attained registration. This work sheds lights on the potential size of demand for a human vaccine for the prevention of visceral and cutaneous leishmaniasis as well as for the prevention and treatment of post-kala-azar dermal leishmaniasis. The analysis is grounded in the definition of vaccine use cases which, by transparently defining different applications of the vaccines in the immunisation programs, provides the basis for defining the target populations and vaccine characteristics. The output of this work, the first-of-its-kind for leishmaniasis, fills a critical information gap and will provide policy makers and vaccine developers with important insights into the public health relevance of a human leishmaniasis vaccine and the strengths of its commercial value proposition. Ultimately this research aims to inform future decisions on disease prioritization and on investments by key stakeholders, as well as to identify areas for further research.

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“…In a similar fashion, we assumed that a CL prophylactic vaccine, while protecting individuals, will have less impact on transmission given the zoonotic nature of this disease, hence immunization will not be stopped in any CL at-risk area. Finally, the impact of a VL prophylactic vaccine on VL incidence and thus, indirectly, also on the size of the target population for the prevention of PKDL was estimated referring to recent disease transmission modelling work for India, where anthroponotic transmission was assumed [44]. In that model (under the assumption that asymptomatic individuals also contribute to VL transmission), the reduction in the number of cases following prophylactic vaccination with a 50% efficacious vaccine covering 100% of the population was estimated to be 30%, 50% and 62% in years 1, 2 and 3 following the introduction of the vaccine [44].…”

Section: Modelling the Targeted Populationmentioning

confidence: 99%

“…Secondly, assumptions concerning the probability of country vaccine introduction are subject to a high degree of uncertainty given that vaccines will likely not be available for another decade. Thirdly, the estimate of the impact of the use of vaccines in the target populations is based on a set of assumptions while awaiting the outcomes of vaccine trials Work done by Erasmus MC (University Medical Center, Rotterdam) provides information on the potential impact of various VL vaccines on VL incidence in an Indian setting [44], but not elsewhere. Whilst our modelling assumptions include transmission by asymptomatic cases of VL, a recent study from India suggests that this may be more limited than previously thought [10].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

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

Malvolti¹,

Malhame²,

Mantel³

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

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“…Significant challenges in leishmaniasis control remain including a lack of effective treatments and drug resistance 10 , a poor understanding of infection reservoir dynamics 11,12 and the limited impact of vector control programmes 13 . The availability of an effective vaccine would have a major impact on health and economic development in low-and-middle income countries (LMICs) where leishmaniasis is endemic, particularly on transmission and population incidence, as well as potentially leading to elimination 14 . To-date no human vaccine for leishmaniasis has been licensed, although several vaccines are being developed [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study)

Parkash

¹

,

Ashwin

²

,

Sádlová

³

et al. 2021

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Background: Leishmaniasis is a globally important yet neglected parasitic disease transmitted by phlebotomine sand flies. With new candidate vaccines in or near the clinic, a controlled human challenge model (CHIM) using natural sand fly challenge would provide a method for early evaluation of prophylactic efficacy. Methods: We evaluated the biting frequency and adverse effects resulting from exposure of human volunteers to bites of either Phlebotomus papatasi or P. duboscqi, two natural vectors of Leishmania major. 12 healthy participants were recruited (mean age 40.2 ± 11.8 years) with no history of significant travel to regions where L. major-transmitting sand flies are prevalent. Participants were assigned to either vector by 1:1 allocation and exposed to five female sand flies for 30 minutes in a custom biting chamber. Bite frequency was recorded to confirm a bloodmeal was taken. Participant responses and safety outcomes were monitored using a visual analogue scale (VAS), clinical examination, and blood biochemistry. Focus groups were subsequently conducted to explore participant acceptability. Results: All participants had at least one successful sand fly bite with none reporting any serious adverse events, with median VAS scores of 0-1/10 out to day 21 post-sand fly bite. Corresponding assessment of sand flies confirmed that for each participant at least 1/5 sand flies had successfully taken a bloodmeal (overall mean 3.67±1.03 bites per participant). There was no significant difference between P. papatasi and P. duboscqi in the number of bites resulting from 5 sand flies applied to human participants (3.3±0.81 vs 3.00±1.27 bites per participant; p=0.56). In the two focus groups (n=5 per group), themes relating to positive participant-reported experiences of being bitten and the overall study, were identified. Conclusions: These results validate a protocol for achieving successful sand fly bites in humans that is safe, well-tolerated and acceptable for participants. Clinicaltrials.gov registration: NCT03999970 (27/06/2019)

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The potential impact of human visceral leishmaniasis vaccines on population incidence

Abstract: Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here:

Cited by 21 publications

References 39 publications

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

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

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

A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study)

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