Insights from mathematical modelling and quantitative analysis on the proposed WHO 2030 targets for visceral leishmaniasis on the Indian subcontinent

Abstract

Visceral leishmaniasis (VL) is a neglected tropical disease (NTD) caused by Leishmania protozoa that are transmitted by female sand flies. On the Indian subcontinent (ISC), VL is targeted by the World Health Organization (WHO) for elimination as a public health problem by 2020, which is defined as <1 VL case (new and relapse) per 10,000 population at district level in Nepal and sub-district level in Bangladesh and India. WHO is currently in the process of formulating 2030 targets, asking whether to maintain the 2020 target or to modify it, while adding a target of zero mortality among detected cases. The NTD Modelling Consortium has developed various mathematical VL transmission models to gain insight into the transmission dynamics of VL, identify the main knowledge gaps, and predict the feasibility of achieving and sustaining the targets by simulating the impact of varying intervention strategies. According to the models, the current target is feasible at the appropriate district/sub-district level in settings with medium VL endemicities (up to 5 reported VL cases per 10,000 population per year) prior to the start of the interventions. However, in settings with higher pre-control endemicities, additional efforts may be required. We also highlight the risk that those with post-kala-azar dermal leishmaniasis (PKDL) may pose to reaching and sustaining the VL targets, and therefore advocate adding control of PKDL cases to the new 2030 targets. Spatial analyses revealed that local hotspots with high VL incidence remain. We warn that the current target provides a perverse incentive to not detect/report cases as the target is approached, posing a risk for truly achieving elimination as a public health problem although this is taken into consideration by the WHO procedures for validation. Ongoing modelling work focuses on the risk of recrudescence when interventions are relaxed after the elimination target has been achieved.

Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India

“…It has been targeted for elimination with the goal of reducing the incidence of VL to below 1/10 000 by the year 2020 [8]. The elimination efforts are working [9] although the targets were reformulated for 2030 [10]. WHO's goals for 2030 are (1) to validate 64 countries for VL elimination as a public health problem-defined as less than 1% case fatality rate due to primary visceral leishmaniasis [11]; and (2) to detect and treat 100% of post kala-azar dermal leishmaniasis (PKDL) cases (by VL post-treatment follow-up for 3 years) [4].…”

How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases

“…A previous collection details the data needs to improve modelling 51 , 84 – 94 , across the NTDs, so great detail will not be provided here. However, for example, VL has a highly variable incubation period, unknown duration of asymptomatic infection and estimates for the duration of lasting immunity are ill-defined 6 , 85 , 95 , introducing uncertainty into the temporal dynamics underlying any projections. Chagas disease, gHAT and leprosy also suffer from relatively long, but indeterminate incubation periods 9 , 12 , 21 impacting case detection and adding greater uncertainty in epidemiological estimates fitted to by models 85 , 96 .…”

How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases

“…The World Health Organization's (WHO) 2021-2030 Neglected Tropical Disease (NTD) Roadmap was launched on January 28 th , 2021, renewing the commitment of the global NTD community to end the suffering caused by these diseases 1 . The development of the roadmap was guided by extensive global stakeholder consultation, including consultation with mathematical and statistical modellers.…”

“…Notable progress to reduce the burden of NTDs has been made as a result of the commitments made in 2012 through the WHO 2020 NTD Roadmap 18 and the London Declaration on NTDs 19 . As a result, 500 million people no longer require interventions against several NTDs and 40 countries, territories and areas have eliminated at least one disease 1 . These wins are the outcome of concerted and consolidated efforts from endemic communities and invaluable volunteers, governments, donor agencies and the pharmaceutical industry.…”

“…Though modelling is increasingly used in public health decision making, the use of modelling to direct clinical trial design and drug development is not so common, and even less so for NTDs. To reach goals like elimination as a public health programme (trachoma, STH, schistosomiasis and LF) and elimination of transmission (onchocerciasis) novel drug development will be critical 1,4,5,11,13,78 . However, financial returns on investments into NTDs are limited and therefore largely unappealing, particularly because of the heavy reliance by endemic nations, on donations from pharmaceutical producers.…”