How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

Achieving Elimination as a Public Health Problem for Schistosoma mansoni and S. haematobium: When Is Community-Wide Treatment Required?

The World Health Organization (WHO) has set elimination as a public health problem (EPHP) as a goal for schistosomiasis. As the WHO treatment guidelines for schistosomiasis are currently under revision, we investigate whether school-based or community-wide treatment strategies are required for achieving the EPHP goal. In low- to moderate-transmission settings with good school enrolment, we find that school-based treatment is sufficient for achieving EPHP. However, community-wide treatment is projected to be necessary in certain high-transmission settings as well as settings with low school enrolment. Hence, the optimal treatment strategy depends on setting-specific factors such as the species present, prevalence prior to treatment, and the age profile of infection.

Measuring heterogeneities in soil-transmitted helminth transmission and control.

The global effort over the past decade to control soil-transmitted helminths (STH) has resulted in communities with endemic infection reaching low prevalence levels suitable for the validation of elimination as a public health problem (EPHP), defined by the World Health Organisation (WHO) as <2% of infections classified as moderate or heavy intensity. The spatial scale in which this is validated is currently undefined. As the burden of STH infection decreases, the degree of aggregation of infection within individuals in a population increases. Identifying these remaining pockets of infection requires fine-scale monitoring and evaluation (M&E) programmes that are rarely implemented within current national neglected tropical disease (NTD) control. This review examines various heterogeneities that characterise the epidemiology of STH infections, and discusses their impact on control policy formulation.

Lymphatic filariases and soil-transmitted helminthiases in Sri Lanka: the challenge of eliminating residual pockets of transmission.

Sri Lanka has successfully met the challenge of controlling both lymphatic filariasis (LF) and soil-transmitted helminthiases (STH) as public health problems. The primary public health strategy for combatting both conditions has been preventive chemotherapy. The national programme for the elimination of LF implemented five annual rounds of mass chemotherapy in the endemic districts from 2002 to 2006 using a combination of diethylcarbamazine and albendazole. The overall microfilaria rate declined from 0.21% in 2001 before the mass chemotherapy, to 0.06% in 2016, at declaration of elimination of LF as a public health problem by the World Health Organization. Currently Sri Lanka is in the phase of post-validation surveillance. Achieving control of STH has been more difficult. Mass deworming programmes have been implemented for nearly a century, and national-level surveys reported prevalence rates declining from 6.9% in 2003 to 1% in 2017. However, neither of these infections has been completely eliminated. A situation analysis indicates continued transmission of both among high-risk communities. This paper explores the reasons for persistence of transmission of both LF and STH in residual pockets and the measures that are required to achieve long-term control, or perhaps even interrupt transmission in Sri Lanka. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Determining the optimal strategies to achieve elimination of transmission for Schistosoma mansoni.

BACKGROUND: In January 2021, the World Health Organization published the 2021-2030 roadmap for the control of neglected tropical diseases (NTDs). The goal for schistosomiasis is to achieve elimination as a public health problem (EPHP) and elimination of transmission (EOT) in 78 and 25 countries (by 2030), respectively. Mass drug administration (MDA) of praziquantel continues to be the main strategy for control and elimination. However, as there is limited availability of praziquantel, it is important to determine what volume of treatments are required, who should be targeted and how frequently treatment must be administered to eliminate either transmission or morbidity caused by infection in different endemic settings with varied transmission intensities. METHODS AND RESULTS: In this paper, we employ two individual-based stochastic models of schistosomiasis transmission developed independently by the Imperial College London (ICL) and University of Oxford (SCHISTOX) to determine the optimal treatment strategies to achieve EOT. We find that treating school-age children (SAC) only is not sufficient to achieve EOT within a feasible time frame, regardless of the transmission setting and observed age-intensity of infection profile. Both models show that community-wide treatment is necessary to interrupt transmission in all endemic settings with low, medium and high pristine transmission intensities. CONCLUSIONS: The required MDA coverage level to achieve either transmission or morbidity elimination depends on the prevalence prior to the start of treatment and the burden of infection in adults. The higher the worm burden in adults, the higher the coverage levels required for this age category through community-wide treatment programmes. Therefore, it is important that intensity and prevalence data are collected in each age category, particularly from SAC and adults, so that the correct coverage level can be calculated and administered.

Disruptions to schistosomiasis programmes due to COVID-19: an analysis of potential impact and mitigation strategies.

BACKGROUND: The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes. METHODS: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium. RESULTS: For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme. CONCLUSIONS: Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.

The impact of mass drug administration on Schistosoma haematobium infection: what is required to achieve morbidity control and elimination?

BACKGROUND: Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%. Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults. Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data. RESULTS: In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed. CONCLUSIONS: We show that the key determinants of achieving the WHO goals are the precise form of the age-intensity of infection profile and the baseline SAC prevalence. Additionally, we find that the higher the burden of infection in adults, the higher the chances that adults need to be included in the treatment programme to achieve EPHP.

Defining Elimination of Genital Warts-A Modified Delphi Study.

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW elimination definition exists. Taking Australia as a case study, we aimed to reach expert consensus on a proposed GW elimination definition using a modified Delphi process. Method: We used modelling and epidemiological data to estimate the expected number of new GW cases, from pre-vaccination (baseline) in 2006 to the year 2060 in Australian heterosexuals, men who have sex with men (MSM), and newly arrived international travellers and migrants. We used these data and the literature, to develop a questionnaire containing ten elimination-related items, each with 9-point Likert scales (1-strongly disagree; 9-strongly agree). The survey was completed by 18 experts who participated in a full day face-to-face modified Delphi study, in which individuals and then small groups discussed and scored each item. The process was repeated online for items where consensus (≥70% agreement) was not initially achieved. Median and coefficient of variation (COV) were used to describe the central tendency and variability of responses, respectively. Findings: There was a 95% participation rate in the face-to-face session, and 84% response rate in the final online round. The median item score ranged between 7.0 and 9.0 and the COV was ≤0.30 on all items. Consensus was reached that at ≥80% HPV vaccination coverage, GW will be eliminated as a public health problem in Australia by 2060. During this time period there will be a 95% reduction in population-level incidence compared with baseline, equivalent to <1 GW case per 10,000 population. The reductions will occur most rapidly in Australian heterosexuals, with 73%, 90% and 97% relative reductions by years 2021, 2030 and 2060, respectively. The proportion of new GW cases attributable to importation will increase from 3.6% in 2006 to ~49% in 2060. Interpretation: Our results indicate that the vaccination programme will minimise new GW cases in the Australian population, but importation of cases will continue. This is the first study to define GW elimination at a national level. The framework developed could be used to define GW elimination in other countries, with thresholds particularly valuable for vaccination programme impact evaluation. Funding: LK supported through an Australian Government Research Training Programme Scholarship; unconditional funding from Seqirus to support the Delphi Workshop.

Insights from mathematical modelling and quantitative analysis on the proposed 2030 goals for trachoma.

Trachoma is a neglected tropical disease and the leading infectious cause of blindness worldwide. The current World Health Organization goal for trachoma is elimination as a public health problem, defined as reaching a prevalence of trachomatous inflammation-follicular below 5% in children (1-9 years) and a prevalence of trachomatous trichiasis in adults below 0.2%. Current targets to achieve elimination were set to 2020 but are being extended to 2030. Mathematical and statistical models suggest that 2030 is a realistic timeline for elimination as a public health problem in most trachoma endemic areas. Although the goal can be achieved, it is important to develop appropriate monitoring tools for surveillance after having achieved the elimination target to check for the possibility of resurgence. For this purpose, a standardized serological approach or the use of multiple diagnostics in complement would likely be required.

Insights from quantitative and mathematical modelling on the proposed WHO 2030 goals for Chagas disease.

Chagas disease (CD) persists as one of the neglected tropical diseases (NTDs) with a particularly large impact in the Americas. The World Health Organization (WHO) recently proposed goals for CD elimination as a public health problem to be reached by 2030 by means of achieving intradomiciliary transmission interruption (IDTI), blood transfusion and transplant transmission interruption, diagnostic and treatment scaling-up and prevention and control of congenital transmission. The NTD Modelling Consortium has developed mathematical models to study Trypanosoma cruzi transmission dynamics and the potential impact of control measures. Modelling insights have shown that IDTI is feasible in areas with sustained vector control programmes and no presence of native triatomine vector populations. However, IDTI in areas with native vectors it is not feasible in a sustainable manner. Combining vector control with trypanocidal treatment can reduce the timeframes necessary to reach operational thresholds for IDTI (<2% seroprevalence in children aged <5 years), but the most informative age groups for serological monitoring are yet to be identified. Measuring progress towards the 2030 goals will require availability of vector surveillance and seroprevalence data at a fine scale, and a more active surveillance system, as well as a better understanding of the risks of vector re-colonization and disease resurgence after vector control cessation. Also, achieving scaling-up in terms of access to treatment to the expected levels (75%) will require a substantial increase in screening asymptomatic populations, which is anticipated to become very costly as CD prevalence decreases. Further modelling work includes refining and extending mathematical models (including transmission dynamics and statistical frameworks) to predict transmission at a sub-national scale, and developing quantitative tools to inform IDTI certification, post-certification and re-certification protocols. Potential perverse incentives associated with operational thresholds are discussed. These modelling insights aim to inform discussions on the goals and treatment guidelines for CD.

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

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.

Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis.

Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within high prevalence settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without interruption of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to S. haematobium. By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.

Tuberculosis en Chile: del control a la eliminación, un camino difícil / Tuberculosis in Chile: from control to elimination, a difficult road

En este artículo se plantea nuevamente el tema de la factibilidad de lograr el objetivo de eliminación de la Tuberculosis y él, en cierto modo es la continuación de otro artículo presentado hace tres años en esta revista por el mismo autor. El análisis se centra ahora, principalmente, en la revisión de los obstáculos que se han debido superar para proseguir los esfuerzos destinados a alcanzar la meta llamada “de eliminación avanzada”, tasa de incidencia de 10 x 100.000, para el año 2010, previa consideración de las dificultades concretas encontradas una vez superado el “umbral de eliminación”. Se hacen presente las líneas de trabajo técnico del programa para los años que siguen y se insiste en que lo principal es que se mantenga la voluntad política de apoyar el Programa de TBC y que los Directores de los Servicios de Salud asuman la responsabilidad central que les corresponde en la consecución de la meta 2010 que es un Objetivo Sanitario del Ministerio.

The feasibility of ing reach the goal of elimination of Tuberculosis in Chile is again discussed. This goal is now a Ministry of Health objective. The intermediate goal, “advanced elimination”, incidence rate of 10 x 100.000 for the year 2010, was designed as, a “Heath Objetive” for the decennium 2000 – 2010. As regards the future perspectives, we analize the obstacles faced in Chile in relation to the possible effects of the new health system structure on the evolution of Tuberculosis in the country. Furthermore, or the possibility of reaching the final goal, will depends on several factors especially related to the growing importance of high risk groups as the total incidence is reduced. It is imperative to develop specific programs for these groups.