Policy Lessons From Quantitative Modeling of Leprosy

Abstract

Recent mathematical and statistical modeling of leprosy incidence data provides estimates of the current undiagnosed population and projections of diagnosed cases, as well as ongoing transmission. Furthermore, modeling studies have been used to evaluate the effectiveness of proposed intervention strategies, such as postleprosy exposure prophylaxis and novel diagnostics, relative to current approaches. Such modeling studies have revealed both a slow decline of new cases and a substantial pool of undiagnosed infections. These findings highlight the need for active case detection, particularly targeting leprosy foci, as well as for continued research into innovative accurate, rapid, and cost-effective diagnostics. As leprosy incidence continues to decline, targeted active case detection primarily in foci and connected areas will likely become increasingly important.

Counting Down the 2020 Goals for 9 Neglected Tropical Diseases: What Have We Learned From Quantitative Analysis and Transmission Modeling?

Abstract

The control of neglected tropical diseases (NTDs) has received huge investment in recent years, leading to large reductions in morbidity. In 2012, the World Health Organization set ambitious targets for eliminating many of these diseases as a public health problem by 2020, an aspiration that was supported by donations of treatments, intervention materials, and funding committed by a broad partnership of stakeholders in the London Declaration on NTDs. Alongside these efforts, there has been an increasing role for quantitative analysis and modeling to support the achievement of these goals through evaluation of the likely impact of interventions, the factors that could undermine these achievements, and the role of new diagnostics and treatments in reducing transmission. In this special issue, we aim to summarize those insights in an accessible way. This article acts as an introduction to the special issue, outlining key concepts in NTDs and insights from modeling as we approach 2020.

Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?

Abstract

Background

Schistosomiasis remains an endemic parasitic disease affecting millions of people around the world. The World Health Organization (WHO) has set goals of controlling morbidity to be reached by 2020, along with elimination as a public health problem in certain regions by 2025. Mathematical models of parasite transmission and treatment impact have been developed to assist in controlling the morbidity caused by schistosomiasis. These models can inform and guide implementation policy for mass drug administration programs, and help design monitoring and evaluation activities.

Methods

We use these models to predict whether the guidelines set by the WHO are on track for achieving their 2020 goal for the control of morbidity, specifically for Schistosoma mansoni. We examine whether programmatic adaptations; namely increases in treatment coverage and/or expansion to adult inclusion in treatment, will improve the likelihood of reaching the WHO goals.

Results

We find that in low-prevalence settings, the goals are likely to be attainable under current WHO guidelines, but in moderate to high-prevalence settings, the goals are less likely to be achieved unless treatment coverage is increased and expanded to at least 85% for school-aged children and 40% for adults.

Conclusions

To improve the likelihood of reaching the WHO goals, programmatic adaptations are required, particularly for moderate- to high-prevalence settings. Furthermore, improvements in adherence to treatment, potential development of candidate vaccines, and enhanced snail control and WASH (water, sanitation, and hygiene) measures will all assist in achieving the goals.

Complementary Paths to Chagas Disease Elimination: The Impact of Combining Vector Control With Etiological Treatment

Abstract

Background

The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals.

Methods

We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age).

Results

Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2–3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years.

Conclusions

Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research.

Investigating the Effectiveness of Current and Modified World Health Organization Guidelines for the Control of Soil-Transmitted Helminth Infections

Abstract

Background

Considerable efforts have been made to better understand the effectiveness of large-scale preventive chemotherapy therapy for the control of morbidity caused by infection with soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura, and the 2 hookworm species, Necator americanus and Ancylostoma duodenale. Current World Health Organization (WHO) guidelines for STH control include mass drug administration (MDA) programs based on prevalence measurements, aiming at reducing morbidity in pre–school-aged children (pre-SAC) and school-aged children (SAC) by lowering the prevalence of moderate- to heavy-intensity infections to <1%.

Methods

We project the likely impact of following the current WHO guidelines and assess whether the WHO morbidity goals will be achieved across a range of transmission settings. We also investigate modifications that could be made to the current WHO treatment guidelines, and project their potential impacts in achieving morbidity and transmission control.

Results

While the standard guidelines are sufficient at low transmission levels, community-wide treatment (ie, involving pre-SAC, SAC, and adults) is essential if WHO morbidity goals are to be met in moderate- to high-transmission settings. Moreover, removing the recommendation of decreasing the treatment frequency at midline (5–6 years after the start of MDA) further improves the likelihood of achieving morbidity control in SAC.

Conclusions

We meld analyses based on 2 mathematical models of parasite transmission and control by MDA for the dominant STH species, to generate a unified treatment approach applicable across all settings, regardless of which STH infection is most common. We recommend clearly defined changes to the current WHO guidelines.

Models of Trachoma Transmission and Their Policy Implications: From Control to Elimination

Abstract

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models

Abstract

Background

With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling.

Methods

We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%.

Results

Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance).

Conclusions

Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Assessing Strategies Against Gambiense Sleeping Sickness Through Mathematical Modeling

Abstract

Background

Control of gambiense sleeping sickness relies predominantly on passive and active screening of people, followed by treatment.

Methods

Mathematical modeling explores the potential of 3 complementary interventions in high- and low-transmission settings.

Results

Intervention strategies that included vector control are predicted to halt transmission most quickly. Targeted active screening, with better and more focused coverage, and enhanced passive surveillance, with improved access to diagnosis and treatment, are both estimated to avert many new infections but, when used alone, are unlikely to halt transmission before 2030 in high-risk settings.

Conclusions

There was general model consensus in the ranking of the 3 complementary interventions studied, although with discrepancies between the quantitative predictions due to differing epidemiological assumptions within the models. While these predictions provide generic insights into improving control, the most effective strategy in any situation depends on the specific epidemiology in the region and the associated costs.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control

Abstract

Background

Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated.

Methods

We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination.

Results

Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control.

Conclusions

Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Policy Recommendations From Transmission Modeling for the Elimination of Visceral Leishmaniasis in the Indian Subcontinent

Abstract

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.

Regarding: "Localized Marked Elongation of the Distal Internal Carotid Artery with or without PHACE Syndrome: Segmental Dolichoectasia of the Distal Internal Carotid Artery" [LETTERS]

Reply: [LETTERS]

Global and Widespread Local White Matter Abnormalities in Juvenile Neuronal Ceroid Lipofuscinosis [PEDIATRICS]

BACKGROUND AND PURPOSE:

Juvenile neuronal ceroid lipofuscinosis is a progressive neurodegenerative lysosomal storage disease of childhood. It manifests with loss of vision, seizures, and loss of cognitive and motor functions leading to premature death. Previous MR imaging studies have reported cerebral and cerebellar atrophy, progressive hippocampal atrophy, thalamic signal intensity alterations, and decreased white matter volume in the corona radiata. However, conventional MR imaging findings are usually normal at younger than 10 years of age. The purpose of our study was to investigate whether diffusion MR imaging could reveal changes in white matter microstructure already present at a younger age.

MATERIALS AND METHODS:

We investigated global and local white matter abnormalities in 14 children with juvenile neuronal ceroid lipofuscinosis (mean age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean age, 11.2 ± 2.3 years; 7 boys). Twelve patients underwent follow-up MR imaging after 2 years (mean age, 11.4 ± 3.2 years; 8 boys). We performed a global analysis using 2 approaches: white matter tract skeleton and constrained spherical deconvolution–based whole-brain tractography. Then, we investigated local microstructural abnormalities using Tract-Based Spatial Statistics.

RESULTS:

We found globally decreased anisotropy (P = .000001) and increased diffusivity (P = .001) in patients with juvenile neuronal ceroid lipofuscinosis. In addition, we found widespread increased diffusivity and decreased anisotropy in, for example, the corona radiata (P < .001) and posterior thalamic radiation (P < .001). However, we found no differences between the first and second acquisitions.

CONCLUSIONS:

The patients with juvenile neuronal ceroid lipofuscinosis exhibited global and local abnormalities in white matter microstructure. Future studies could apply more specific microstructural models and study whether these abnormalities are already present at a younger age.

Detection of the Stellate and Thoracic Sympathetic Chain Ganglia with High-Resolution 3D-CISS MR Imaging [SPINE]

BACKGROUND AND PURPOSE:

Despite the importance of the sympathetic nervous system in homeostasis and its putative role in various disease states, little is known regarding our ability to image the sympathetic chain and sympathetic chain ganglia, perhaps owing to their small size. In this retrospective study, we sought to evaluate the normal anatomy of the sympathetic chain ganglia and assess the detectability of the sympathetic chain and sympathetic chain ganglia on high-resolution 3D-CISS images.

MATERIALS AND METHODS:

This study included 29 patients who underwent 3D-CISS MR imaging of the thoracic spine for reasons unrelated to abnormalities of the sympathetic nervous system. Patients with a prior spinal operation or visible spinal pathology were excluded. The sympathetic chain ganglia were evaluated using noncontrast 3D-CISS MR imaging. Statistical analyses included t tests and measures of central tendency. The Cohen statistic was calculated to evaluate interrater reliability.

RESULTS:

The stellate ganglion and thoracic chain ganglia were identified in all subjects except at the T10–T11 and T11–T12 levels. The stellate ganglion was found inferomedial to the subclavian artery and anterior and inferior to the transverse process of C7 in all subjects. Thoracic sympathetic chain ganglia were identified ventral to the costovertebral junction in all subjects from T2 to T10. There was strong interobserver agreement for the detection of the sympathetic chain ganglia with > 0.80. The size, shape, and location of these structures corresponded with gross anatomic and surgical observations.

CONCLUSIONS:

The thoracic sympathetic chain ganglia can be identified on precontrast 3D-CISS MR imaging. This technique may aid in the initial evaluation of stellate ganglion and/or sympathetic chain ganglia size and signal change for comparison in future studies.

Reversible Dilation of the Superior Ophthalmic Vein in Intubated Patients [HEAD & NECK]

BACKGROUND AND PURPOSE:

Superior ophthalmic vein enlargement has typically been associated with increased intracranial or orbital pressure. This study evaluates the incidence of superior ophthalmic vein enlargement in intubated patients without pre-existing intracranial or intraorbital pathologies.

MATERIALS AND METHODS:

Two cohorts (patients with trauma and epilepsy patients undergoing stereotactic intracranial lead placement) who underwent CT while intubated and shortly following extubation and a cohort of 30 outpatients with a history of headache and normal head CT findings (healthy controls) were included. The superior ophthalmic vein diameter was measured on all scans.

RESULTS:

Seventy patients intubated for trauma and 45 patients with intraoperative CT were included (n = 115). While intubated, 66% of the total sample had at least unilateral superior ophthalmic vein dilation of >2.5 mm and 48% had bilateral dilation. Fifty-seven percent of patients with trauma and 84% of intraoperative patients with dilated superior ophthalmic veins showed reversal of mean superior ophthalmic vein dilation to <2.5 mm on postextubation CT. The mean superior ophthalmic vein diameter decreased an average of 1.2 mm following extubation. Changes in superior ophthalmic vein diameter between intubated and extubated states were statistically significant (P < .001). Differences between the control group and the extubated subjects were not statistically significant (P = .21).

CONCLUSIONS:

Bilateral dilation of the superior ophthalmic vein is common in intubated patients and usually reverses following extubation. In the appropriate clinical setting, this knowledge will prevent misinterpretation of prominent superior ophthalmic veins as automatically indicative of an underlying pathology.

Geochemical, radiometric, and environmental approaches for the assessment of the intensity and chronology of metal contamination in the sediment cores from Oualidia lagoon (Morocco)

Abstract

The present study evaluates the distribution of metals over the last 100 years in the Oualidia lagoon by examining their concentrations in the sediment cores. The samples were analyzed by instrumental neutron activation analysis and inductively coupled plasma mass spectrometry. Activities of ²¹⁰Pb, ²²⁶Ra, and ¹³⁷Cs were determined by gamma-ray spectrometry for establishing the age-depth relationships throughout the sediment cores by applying conventional models. The results indicated that the study area is contaminated by As and Cd revealing a detectable anthropogenic input of occurring metals as a consequence of the continuous development of human activities around the lagoon since 1950. The enrichment factor calculated for each layer of the three cores revealed that the studied sediments present no enrichment by Pb, K, and Mn; minor enrichment by Zn, Cr, Co, Cu, V, and Ni; and a moderately to severe enrichment by As and Cd. The pollution load index values increase from the bottom to the top of cores, and ranged from 0.9 to 2.8, which indicates levels of pollutants ranging from background to relatively high concentrations in the investigated sediments.

Investigating the effect of MgO and CeO 2 metal nanoparticle on the gasoline fuel properties: empirical modeling and process optimization by surface methodology

Abstract

The main purpose of this paper is to investigate how to optimize gasoline in order to reduce the emitted pollutants caused by combustion, while the torque and power of the engine reach the maximum capabilities. To optimize gasoline formulation, an ethanol and magnesium oxide (MgO) or cerium oxide (CeO₂) mixture was added to gasoline. This study explores the role of main variables such as type of metal nanoparticle additive, engine speed, and throttle on engine performance and exhaust gas emissions through the modeling and optimization methods. Experimental design conducted through the implementation of D-optimal design, taking into account the three main parameters. To review the efficiency of this novel fuel, it was tested by a four-stroke engine connected to a dynamometer and an analyzer, under different controlled environments: speeds of 1500, 2000, 2500, and 3000 rpm at both half and full throttle conditions. The analyzed data are the power and torque of the engine, the amount of emitted CO, CO₂, HC, and NO_x, the octane index, and the viscosity. The analyzed data were calculated and turned into models. Applying the models to data (the optimization process), close correlation between predicted and actual outcomes was found, highlighting the validity of the work. A secondary finding is that the CeO₂ mixture used at higher speeds and throttles produces less emissions, while lower speeds and throttles using the MgO mixture produce less emissions.

Anti-Pruritic and Anti-Inflammatory Effects of Oxymatrine in a Mouse Model of Allergic Contact Dermatitis

Allergic contact dermatitis (ACD) [1] is a highly prevalent inflammatory disease of the skin, which is mediated by hapten-specific T-cells and caused by repeated exposure of the skin to the same hapten [2]. ACD usually presents with inflammatory responses including erythema, swelling and immune imbalances. Patients with ACD often also exhibit refractory pruritus. Pruritus is an uncomfortable sensation which can trigger the urge to scratch [3]. Refractory pruritus, also called chronic pruritus, occurs repeatedly and negatively affects attention and sleep quality.

“Determination of the impact of melanoma surgical timing on survival using the National Cancer Database”

Association of family structure with atopic dermatitis in United States children

The relationship between family structure and atopic dermatitis has not previously been elucidated., Children from family structures without two married, biological parents have increased odds of AD and poorer overall health outcomes., Children from family structures without two, married, biological parents may benefit from increased surveillance, closer follow-up and optimized treatment for incident AD.