ABSTRACT
BACKGROUND: Control of visceral leishmaniasis (VL) on the Indian subcontinent has been highly successful. Control efforts such as indoor residual spraying and active case detection will be scaled down or even halted over the coming years. We explored how after scale-down, potential recurrence of VL cases may be predicted based on population-based surveys of antibody or antigenemia prevalence. METHODS: Using a stochastic age-structured transmission model of VL, we predicted trends in case incidence and biomarker prevalence over time after scaling down control efforts when the target of 3 successive years without VL cases has been achieved. Next, we correlated biomarker prevalence with the occurrence of new VL cases within 10 years of scale-down. RESULTS: Occurrence of at least 1 new VL case in a population of 10 000 was highly correlated with the seroprevalence and antigenemia prevalence at the moment of scale-down, or 1 or 2 years afterward. Receiver operating characteristic curves indicated that biomarker prevalence in adults provided the most predictive information, and seroprevalence was a more informative predictor of new VL cases than antigenemia prevalence. Thresholds for biomarker prevalence to predict occurrence of new VL cases with high certainty were robust to variation in precontrol endemicity. CONCLUSIONS: The risk of recrudescence of VL after scaling down control efforts can be monitored and mitigated by means of population-based surveys. Our findings highlight that rapid point-of-care diagnostic tools to assess (preferably) seroprevalence or (otherwise) antigenemia in the general population could be a key ingredient of sustainable VL control.
Subject(s)
Leishmaniasis, Visceral , Adult , Child, Preschool , Humans , Incidence , Longitudinal Studies , Prevalence , Seroepidemiologic StudiesABSTRACT
Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.
Subject(s)
COVID-19 , Tropical Medicine , Humans , Neglected Diseases/epidemiology , Pandemics , SARS-CoV-2ABSTRACT
BACKGROUND: Control of visceral leishmaniasis (VL) on the Indian subcontinent relies on prompt detection and treatment of symptomatic cases. Detection efforts influence the observed VL incidence and how well it reflects the underlying true incidence. As control targets are defined in terms of observed cases, there is an urgent need to understand how changes in detection delay and population coverage of improved detection affect VL control. METHODS: Using a mathematical model for transmission and control of VL, we predict the impact of reduced detection delays and/or increased population coverage of the detection programs on observed and true VL incidence and mortality. RESULTS: Improved case detection, either by higher coverage or reduced detection delay, causes an initial rise in observed VL incidence before a reduction. Relaxation of improved detection may lead to an apparent temporary (1 year) reduction in VL incidence, but comes with a high risk of resurging infection levels. Duration of symptoms in detected cases shows an unequivocal association with detection effort. CONCLUSIONS: VL incidence on its own is not a reliable indicator of the performance of case detection programs. Duration of symptoms in detected cases can be used as an additional marker of the performance of case detection programs.
Subject(s)
Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/prevention & control , Disease Eradication , Humans , Incidence , India/epidemiology , Leishmaniasis, Visceral/epidemiology , Models, BiologicalABSTRACT
Background: Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods: This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results: The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions: The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks.
Subject(s)
Disease Eradication/legislation & jurisprudence , Insecticides/administration & dosage , Leishmaniasis, Visceral/prevention & control , Models, Theoretical , Phlebotomus/parasitology , Animals , Female , Humans , Incidence , India/epidemiology , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/transmission , Policy , Public Health , World Health OrganizationABSTRACT
Background: In 2023 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared endemic, yet hospital admissions have persisted and risen within populations at high and moderate risk of developing severe disease, which include those of older age, and those with co-morbidities. Antiviral treatments, currently only available for high-risk individuals, play an important role in preventing severe disease and hospitalisation within this subpopulation. Here, we further explore the public health and economic benefits of extending target populations for treatment, and assess efficacy thresholds for a treatment strategy to be cost-saving. Methods: We adapted an individual-based transmission model of SARS-CoV-2, OpenCOVID, which was calibrated and validated to 2020-2023 Swiss, European, and Northern Hemisphere epidemiological data. We used the model to estimate hospitalisations and overall costs for preventatively treating three risk groups for a full range of treatment efficacies and coverages with, besides vaccination and hospital treatments, no other interventions in place. We further calculated efficacy thresholds for strategies to be cost-saving. A global sensitivity analysis was conducted to test the sensitivity of all outcomes for a wide range of treatment properties, emerging variant properties, and vaccination coverages. Findings: In a high vaccination coverage setting, we found that a high efficacy antiviral treatment given to all those at high-risk could reduce hospitalisations by up to 40%. When expanding treatment coverage to also include all those at moderate-risk, an additional 50% of hospitalisations could be averted. Targeting both high-risk and moderate-risk groups was found to be cost-saving for a treatment efficacy greater than â¼40%. This threshold was found to be robust regardless of vaccination coverage and emerging variant properties, but highly sensitive to treatment costs. Interpretation: For a sufficiently efficacious antiviral treatment, expanding the target population to include both high-risk and moderate-risk groups should be considered. Equitable treatment costs are found crucial in achieving the best possible public health and health economic outcomes. Funding: Botnar Research Centre for Child Health (DZX2165 to MAP), the Swiss National Science Foundation Professorship of MAP (P00P3_203450) and Swiss National Science Foundation NFP 78 Covid-19 2020 (4079P0_198428 to MAP).
ABSTRACT
This short communication reflects upon the challenges and recommendations of multiple COVID-19 modelling and data analytic groups that provided quantitative evidence to support health policy discussions in Switzerland and Germany during the SARS-CoV-2 pandemic. Capacity strengthening outside infectious disease emergencies will be required to enable an environment for a timely, efficient, and data-driven response to support decisions during any future infectious disease emergency. This will require 1) a critical mass of trained experts who continuously advance state-of-the-art methodological tools, 2) the establishment of structural liaisons amongst scientists and decision-makers, and 3) the foundation and management of data-sharing frameworks.
Subject(s)
COVID-19 , Communicable Diseases , Humans , Public Health , Emergencies , COVID-19/epidemiology , SARS-CoV-2 , Communicable Diseases/epidemiologyABSTRACT
Leishmania infections are global, occurring in 98 countries and all World Health Organization (WHO) regions with 600 million to 1 billion people at risk of infection. Visceral leishmaniasis is associated with almost 20,000 reported deaths annually, with children under 5 years of age being at the greatest risk of mortality. Amongst WHO-recognised Neglected Tropical Diseases (NTDs), leishmaniasis is one of the most important in terms of mortality and morbidity. With an increasing global burden of disease and a growing threat from climate change, urbanisation and drug resistance, there remains an imperative to develop leishmaniasis vaccines. New tools to understand correlates of protection and to assess vaccine efficacy are being developed to ease the transition into larger scale efficacy trials or provide alternate routes to licensure. Early indications suggest a diverse portfolio of manufacturers exists in endemic countries with an appetite to develop leishmaniasis vaccines. This Vaccine Value Profile (VVP) provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of leishmaniasis vaccines. The leishmaniasis VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the leishmaniasis VVP and have collectively described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.
Subject(s)
Leishmaniasis Vaccines , Leishmaniasis, Visceral , Leishmaniasis , Child , Humans , Child, Preschool , Leishmaniasis Vaccines/therapeutic use , Leishmaniasis/prevention & control , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/prevention & control , Public Health , Morbidity , Neglected Diseases/prevention & controlABSTRACT
Background: SARS-CoV-2 variants of concern, such as Omicron (B.1.1.529), continue to emerge. Assessing the impact of their potential viral properties on the probability of future transmission dominance and public health burden is fundamental in guiding ongoing COVID-19 control strategies. Methods: With an individual-based transmission model, OpenCOVID, we simulated three viral properties; infectivity, severity, and immune-evading ability, all relative to the Delta variant, to identify thresholds for Omicron's or any emerging VOC's potential future dominance, impact on public health, and risk to health systems. We further identify for which combinations of viral properties current interventions would be sufficient to control transmission. Results: We show that, with first-generation SARS-CoV-2 vaccines and limited physical distancing in place, a VOC's potential future dominance is primarily driven by its infectivity, which does not always lead to an increased public health burden. However, we also show that highly immune-evading variants that become dominant, even in the case of reduced variant severity, would likely require alternative measures to avoid strain on health systems, such as strengthened physical distancing measures, novel treatments, and second-generation vaccines. Expanded vaccination, that includes a booster dose for adults and child vaccination strategies, is projected to have the biggest public health benefit for a highly infective, highly severe VOC with low immune-evading capacity. Conclusions: These findings provide quantitative guidance to decision-makers at a critical time while Omicron's properties are being assessed and preparedness for emerging VOCs is eminent. We emphasise the importance of both genomic and population epidemiological surveillance.
ABSTRACT
BACKGROUND: Vaccinations have reduced severe burden of COVID-19 and allowed for lifting of non-pharmaceutical interventions. However, with immunity waning alongside emergence of more transmissible variants of concern, vaccination strategies must be examined. METHODS: Here we apply a SARS-CoV-2 transmission model to identify preferred frequency, timing, and target groups for vaccine boosters to reduce public health burden and health systems risk. We estimated new infections and hospital admissions averted over 2 years through annual or biannual boosting of those eligible (those who received doses one and two) who are (1) most vulnerable (60+ or living with comorbidities) or (2) those 5+, at universal (98% of eligible) or lower coverage (85% of those 50+ or with comorbidities and 50% of 5-49 year olds) representing moderate vaccine fatigue and/or hesitancy. We simulated three emerging variant scenarios: (1) no new variants; (2) 25% more infectious and immune-evading Omicron-level severity variants emerge annually and become dominant; (3) emerge biannually. We further explored the impact of varying seasonality, variant immune-evading capacity, infectivity, severity, timing, and vaccine infection blocking assumptions. RESULTS: To reduce COVID-19-related hospitalisations over the next 2 years, boosters should be provided for all those eligible annually 3-4 months ahead of peak winter whether or not new variants of concern emerge. Only boosting those most vulnerable is unlikely to ensure reduced stress on health systems. Moreover, boosting all eligible better protects those most vulnerable than only boosting the vulnerable group. Conversely, while this strategy may not ensure reduced stress on health systems, as an indication of cost-effectiveness, per booster dose more hospitalisations could be averted through annual boosting of those most vulnerable versus all eligible, since those most vulnerable are more likely to seek hospital care once infected, whereas increasing to biannual boosting showed diminishing returns. Results were robust when key model parameters were varied. However, we found that the more frequently variants emerge, the less the effect boosters will have, regardless of whether administered annually or biannually. CONCLUSIONS: Delivering well-timed annual COVID-19 vaccine boosters to all those eligible, prioritising those most vulnerable, can reduce infections and hospital admissions. Findings provide model-based evidence for decision-makers to plan for administering COVID-19 boosters ahead of winter 2022-2023 to help mitigate the health burden and health system stress.
ABSTRACT
BACKGROUND: As vaccination coverage against SARS-CoV-2 increases amidst the emergence and spread of more infectious and potentially more deadly viral variants, decisions on timing and extent of relaxing effective, but unsustainable, non-pharmaceutical interventions (NPIs) need to be made. METHODS: An individual-based transmission model of SARS-CoV-2 dynamics, OpenCOVID, was developed to compare the impact of various vaccination and NPI strategies on the COVID-19 epidemic in Switzerland. OpenCOVID uses the Oxford Containment Health Index (OCHI) to quantify the stringency of NPIs. RESULTS: Even if NPIs in place in March 2021 were to be maintained and the vaccine campaigns rollout rapidly scaled-up, a 'third wave' was predicted. However, we find a cautious phased relaxation can substantially reduce population-level morbidity and mortality. We find that a faster vaccination campaign can offset the size of such a wave, allowing more flexibility for NPIs to be relaxed sooner. Model outcomes were most sensitive to the level of infectiousness of variants of concern observed in Switzerland. CONCLUSION: A rapid vaccination rollout can allow the sooner relaxation of NPIs, however ongoing surveillance of - and swift responses to - emerging viral variants is of utmost importance for epidemic control.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Switzerland/epidemiology , VaccinationABSTRACT
BACKGROUND: In line with movement restrictions and physical distancing essential for the control of the COVID-19 pandemic, WHO recommended postponement of all neglected tropical disease (NTD) control activities that involve community-based surveys, active case finding, and mass drug administration in April, 2020. Following revised guidance later in 2020, and after interruptions to NTD programmes of varying lengths, NTD programmes gradually restarted in the context of an ongoing pandemic. However, ongoing challenges and service gaps have been reported. This study aimed to evaluate the potential effect of the programmatic interruptions and strategies to mitigate this effect. METHODS: For seven NTDs, namely soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma, visceral leishmaniasis, and human African trypanosomiasis, we used mathematical transmission models to simulate the effect of programme interruptions on the dynamics of each of these diseases in different endemic settings. We also explored the potential benefit of implementing mitigation strategies, primarily in terms of minimising the delays to control targets. FINDINGS: We show that the effect of the COVID-19-induced interruption in terms of delay to achieving elimination goals might in some cases be much longer than the duration of the interruption. For schistosomiasis, onchocerciasis, trachoma, and visceral leishmaniasis, a mean delay of 2-3 years for a 1-year interruption is predicted in areas of highest prevalence. We also show that these delays can largely be mitigated by measures such as additional mass drug administration or enhanced case-finding. INTERPRETATION: The COVID-19 pandemic has brought infectious disease control to the forefront of global consciousness. It is essential that the NTDs, so long neglected in terms of research and financial support, are not overlooked, and remain a priority in health service planning and funding. FUNDING: Bill & Melinda Gates Foundation, Medical Research Council, and the UK Foreign, Commonwealth & Development Office.
Subject(s)
COVID-19 , Leishmaniasis, Visceral , Onchocerciasis , Schistosomiasis , Trachoma , Tropical Medicine , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Leishmaniasis, Visceral/epidemiology , Neglected Diseases/epidemiology , Neglected Diseases/prevention & control , Onchocerciasis/prevention & control , Pandemics , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Soil , Trachoma/epidemiologyABSTRACT
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.
Subject(s)
Leishmaniasis Vaccines/immunology , Leishmaniasis Vaccines/supply & distribution , Leishmaniasis/epidemiology , Leishmaniasis/prevention & control , Global Health , Humans , Leishmaniasis Vaccines/economics , Public HealthABSTRACT
BACKGROUND: In March 2020, India declared a nationwide lockdown to control the spread of coronavirus disease 2019. As a result, control efforts against visceral leishmaniasis (VL) were interrupted. METHODS: Using an established age-structured deterministic VL transmission model, we predicted the impact of a 6- to 24-month programme interruption on the timeline towards achieving the VL elimination target as well as on the increase of VL cases. We also explored the potential impact of a mitigation strategy after the interruption. RESULTS: Delays towards the elimination target are estimated to range between 0 and 9 y. Highly endemic settings where control efforts have been ongoing for 5-8 y are most affected by an interruption, for which we identified a mitigation strategy to be most relevant. However, more importantly, all settings can expect an increase in the number of VL cases. This increase is substantial even for settings with a limited expected delay in achieving the elimination target. CONCLUSIONS: Besides implementing mitigation strategies, it is of great importance to try and keep the duration of the interruption as short as possible to prevent new individuals from becoming infected with VL and continue the efforts towards VL elimination as a public health problem in India.
Subject(s)
COVID-19/epidemiology , Communicable Disease Control/organization & administration , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/prevention & control , Humans , India/epidemiology , Neglected Diseases/epidemiology , Neglected Diseases/prevention & control , Pandemics , SARS-CoV-2ABSTRACT
Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.
Subject(s)
Communicable Disease Control/methods , Data Collection/methods , Neglected Diseases/epidemiology , Neglected Diseases/prevention & control , Elephantiasis, Filarial/epidemiology , Elephantiasis, Filarial/transmission , Humans , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/transmission , Models, Theoretical , Onchocerciasis/epidemiology , Onchocerciasis/transmission , Schistosomiasis/epidemiology , Schistosomiasis/transmission , Soil/parasitology , Trachoma/epidemiology , Trachoma/transmission , Tropical Medicine/methods , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/transmissionABSTRACT
Leishmania infantum is transmitted by sand flies and causes visceral leishmaniasis (VL) in humans, as well as canine leishmaniosis (CanL) in dogs, the main reservoir of infection in Europe. The infection spread northwards in the last two decades, but case data are scarce, hindering monitoring and evaluation of incidence as is required by European WHO guidelines. We aim to identify the current geographical distribution of CanL incidence in Spain, which has been endemic for CanL, and France, where CanL is emerging. An online survey was conducted among veterinarians in Spain and France questioning CanL incidence in the years 2016-2017. These data were interpolated to estimate incidence in both countries using the geographical analysis ordinary kriging. Two hundred and seventy-three (273) veterinarians from 81 out of 148 French and Spanish districts completed the survey. The mean incidence in veterinary practices was 21 CanL cases per 1000 dogs during the past year, which was higher in Spain (31/1000 dogs/year) than in France (6/1000 dogs/year). Incidence rates were highest in south-eastern Spain, but sporadic cases were found up to the most northern regions of France. Our study confirms the northward spread of CanL in Spain and France, as the incidence rates were higher than reported in previous studies and cases were found in areas formerly considered non-endemic for L. infantum. Monitoring the reservoir of infection in dogs is essential for implementing timely and geographically-targeted interventions to prevent further spread of CanL and VL in Europe.
Subject(s)
Dog Diseases , Leishmaniasis , Animals , Dog Diseases/epidemiology , Dog Diseases/prevention & control , Dogs , France/epidemiology , Incidence , Leishmaniasis/veterinary , Spain/epidemiologyABSTRACT
INTRODUCTION: The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. AREAS COVERED: We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. EXPERT OPINION: Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.
Subject(s)
Leishmania , Leishmaniasis Vaccines , Leishmaniasis , Animals , Humans , Leishmaniasis/prevention & control , VaccinationABSTRACT
Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence. We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as a public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years' time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact. Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.
Subject(s)
Leishmaniasis Vaccines/immunology , Leishmaniasis, Cutaneous/prevention & control , Leishmaniasis, Visceral/epidemiology , Humans , Incidence , India/epidemiology , Leishmaniasis, Visceral/prevention & control , Public HealthABSTRACT
BACKGROUND: Nepal launched a visceral leishmaniasis (also known as kala-azar) elimination initiative in 2005. We primarily aimed to assess whether transmission of Leishmania donovani had decreased since the launch of the initiative. We also assessed the validity of the direct agglutination test (DAT) as a marker of infection, in view of future surveillance systems. METHODS: We did a repeat survey in a population aged 2 years and older for whom baseline serological data were available from 2006. Data were from three districts in the eastern region of Nepal. The primary outcome of interest was prevalent infection with L donovani as measured with DAT (cutoff value ≥1:3200). We compared age group-specific and cluster-specific seroprevalences in 2016 with those in 2006, using χ2 tests, with a specific focus on the comparison of seroprevalences in children born between 1996 and 2005, and those born between 2006 and 2015. To estimate the overall adjusted risk ratio for being seropositive in 2016 compared with 2006, we fitted a Poisson model controlling for age, sex, and cluster. FINDINGS: Between Oct 17, 2016, and Dec 26, 2016, we assessed 6609 individuals. DAT prevalence in children younger than 10 years was 4·1% (95% CI 3·2-5·4) in 2006 versus 0·5% (0·1-1·7) in 2016 (p<0·0001). Seroprevalence was lower in 2016 than in 2006 in all age groups and in all repeated clusters. The overall adjusted risk ratio of being seropositive was 0·44 (95% CI 0·37-0·52) for 2016 compared with 2006, and 0·04 (0·01-0·16) in children younger than 10 years. INTERPRETATION: Our findings show that transmission of L donovani in Nepal has decreased significantly between 2006 and 2016, coinciding with the elimination programme. DAT seems useful for monitoring of L donovani transmission. FUNDING: The Directorate-General for Development Cooperation of Belgium.
Subject(s)
Disease Eradication/statistics & numerical data , Disease Eradication/trends , Endemic Diseases/prevention & control , Leishmania donovani/immunology , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/prevention & control , Leishmaniasis, Visceral/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Endemic Diseases/statistics & numerical data , Female , Forecasting , Humans , Male , Middle Aged , Nepal/epidemiology , Risk Factors , Seroepidemiologic Studies , Surveys and Questionnaires , Young AdultABSTRACT
Post-kala-azar dermal leishmaniasis (PKDL) is a parasitic skin infection which can occur after visceral leishmaniasis (VL). Recent xenodiagnosis studies (Mondal et al., Clin. Infect. Dis., 2018) have uncovered the infectiousness of PKDL. When including this in a transmission model, PKDL cases appear as an important reservoir of infection, likely frustrating the VL elimination efforts on the Indian subcontinent.
Subject(s)
Leishmaniasis, Cutaneous , Leishmaniasis, Visceral , Psychodidae , AnimalsABSTRACT
Zoonotic visceral leishmaniasis (ZVL) is a parasitic disease affecting dogs and humans, which is transmitted by female sandflies. Over the last decade, disease prevalence has increased fivefold in parts of southern Europe, where an estimated 2.5 million dogs are infected. This increase is mainly due to an expansion in sandfly distribution due to climate change and to the greater numbers of dogs travelling among European countries. To combat the spread of ZVL in Europe, international guidelines have been drawn up that describe strategies to prevent, control and monitor the disease. To investigate whether these strategies are being implemented in the field, we conducted an online survey among veterinarians in Spain (endemic for ZVL) and France (south: emerging; north: non-endemic). Of the 889 respondents, 459 veterinarians completed all questions. Although 60% of all veterinarians were aware of the current ZVL increase in Europe, 70% were not familiar with any guidelines for controlling the disease. Most of their preventive and treatment actions were, however, in line with intervention strategies recommended by the guidelines. From the veterinarians in this survey, 76% had received no reports regarding confirmed cases of canine leishmaniosis (CanL) or human visceral leishmaniasis in their region or country. The fact that 88% of confirmed cases of clinical CanL were not reported suggests inadequate disease monitoring and evaluation. We therefore recommend that an easy-to-use and accessible international online network be developed, where both veterinarians and physicians can report confirmed cases of leishmaniosis in dogs and humans. This is crucial for monitoring, controlling and preventing the further spread of ZVL in Europe at regional, national and international level.