A tale of two parasites:statistical modelling to support disease control programmes in Africa

Vector-borne diseases have long presented major challenges to the health of rural communities in the wet tropical regions of the world, but especially in sub-Saharan Africa. In this paper we describe the contribution that statistical modelling has made to the global elimination programme for one vector-borne disease, onchocerciasis. We explain why information on the spatial distribution of a second vector-borne disease, Loa loa, is needed before communities at high risk of onchocerciasis can be treated safely with mass distribution of ivermectin, an antifiarial medication. We show how a model-based geostatistical analysis of Loa loa prevalence survey data can be used to map the predictive probability that each location in the region of interest meets a WHO policy guideline for safe mass distribution of ivermectin and describe two applications: one is to data from Cameroon that assesses prevalence using traditional blood-smear microscopy; the other is to Africa-wide data that uses a low-cost questionnaire-based method. We describe how a recent technological development in image-based microscopy has resulted in a change of emphasis from prevalence alone to the bivariate spatial distribution of prevalence and the intensity of infection amongst infected individuals. We discuss how statistical modelling of the kind described here can contribute to health policy guidelines and decisionmaking in two ways. One is to ensure that, in a resource-limited setting, prevalence surveys are designed, and the resulting data analysed, as efficiently as possible. The other is to provide an honest quantification of the uncertainty attached to any binary decision by reporting predictive probabilities that a policy-defined condition for action is or is not met. Vector-borne diseases have long presented major challenges to the health of rural communities in the wet tropical regions of the world, but especially in sub-Saharan Africa. In this paper we describe the contribution that statistical modelling has made to the global elimination programme for one vector-borne disease, onchocerciasis. We explain why information on the spatial distribution of a second vector-borne disease, Loa loa, is needed before communities at high risk of onchocerciasis can be treated safely with mass distribuiton of ivermectin, an antiflarial medication. We show how a model-based geostatistical analysis of Loa loa prevalence survey data can be used to map the predictive probability that each location in the region of interest meets a WHO policy guideline for safe mass distribution of ivermectin and describe two applications: one to data from Cameroon that assesses prevalence using traditional blood-smear microscopy; one to Africa-wide data that uses a low-cost questionnaire-based method. We describe how a recent technological development in image-based microscopy has resulted in a change of emphasis from prevalence alone to the bivariate spatial distribution of prevalence and the intensity of infection amongst infected individuals. We discuss how statistical modelling of the kind described here can contribute to health policy guidelines and decision-making in two ways. One is to ensure that, in a resourcelimited setting, prevalece surveys are designed, and the resulting data analysed, as efficiently as possible. The other is to provide an honest quantification of the uncertainy attached to any binary decision by reporting predictive probabilities that a policy-defined condition for action is or is not met

Circadian Disruption, \u3cem\u3ePer3\u3c/em\u3e, and Human Cytokine Secretion

Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n=70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-I ra, IL-I-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may play a role

Baseline mapping of neglected tropical diseases in Africa: the accelerated WHO/AFRO mapping project

Mapping is a prerequisite for effective implementation of interventions against neglected tropical diseases (NTDs). Before the accelerated World Health Organization (WHO)/Regional Office for Africa (AFRO) NTD Mapping Project was initiated in 2014, mapping efforts in many countries were frequently carried out in an ad hoc and nonstandardized fashion. In 2013, there were at least 2,200 different districts (of the 4,851 districts in the WHO African region) that still required mapping, and in many of these districts, more than one disease needed to be mapped. During its 3-year duration from January 2014 through the end of 2016, the project carried out mapping surveys for one or more NTDs in at least 2,500 districts in 37 African countries. At the end of 2016, most (90%) of the 4,851 districts had completed the WHO-required mapping surveys for the five targeted Preventive Chemotherapy (PC)-NTDs, and the impact of this accelerated WHO/AFRO NTD Mapping Project proved to be much greater than just the detailed mapping results themselves. Indeed, the AFRO Mapping Project dramatically energized and empowered national NTD programs, attracted donor support for expanding these programs, and developed both a robust NTD mapping database and data portal. By clarifying the prevalence and burden of NTDs, the project provided not only the metrics and technical framework for guiding and tracking program implementation and success but also the research opportunities for developing improved diagnostic and epidemiologic sampling tools for all 5 PC-NTDs-lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma

Walking outside Improves Mood for Healthy Postmenopausal Women

Background Exercise has been shown to decrease breast cancer risk and slow the progression of breast cancer. Physician recommendations and clinical research data most often are for gym-based exercise programs. However, the importance of exercise location on mood and stress hormones that may influence adherence to exercise has not been addressed. Methods Women first walked for an hour outdoors along a university path and then a week later, for an hour indoors on a treadmill in a typical gym environment. Pre and post outdoor and indoor exercise moods (happy, pleased, sad, frustrated, worried, angry, delighted, and joy) were assessed by a 6 point Likert questionnaire, and saliva samples were collected for analysis of cortisol, and alpha amylase (a surrogate for serum norepinephrine). Results Nineteen healthy, non-smoking, postmenopausal women (average age 58 ± 4) participated. Compared with scores after walking outdoors, walking indoors was associated with higher scores of worry (p = 0.02; mean difference 0.9; 95% CI (0.17, 1.6) and frustration (p = 0.03; mean difference 0.9; 95% CI (0.12, 1.6), and lower scores for feelings of being pleased (p = 0.03; mean difference -0.8; 95% CI: -1.7, 0.1) and delighted (p = 0.05; mean difference -0.9; 95% CI: -1.75, -0.02). Changes in salivary hormone levels did not vary significantly between the two environments. Conclusion Walking outdoors was associated with improved mood, but walking indoors was not. Improved mood may reduce breast cancer risk indirectly by promoting regular exercise. Physician recommendations for exercise should include gym and non-gym based exercise options

Number of Mectizan tablets (3 mg or equivalent) shipped from 1988 to 2013.

<p>Number of Mectizan tablets (3 mg or equivalent) shipped from 1988 to 2013.</p

An Integrated District Mapping Strategy for Loiasis to Enable Safe Mass Treatment for Onchocerciasis in Gabon

The lack of a WHO-recommended strategy for onchocerciasis treatment with ivermectin in hypo-endemic areas co-endemic with loiasis is an impediment to global onchocerciasis elimination. New loiasis diagnostics (LoaScope; Loa antibody rapid test) and risk prediction tools may enable safe mass treatment decisions in co-endemic areas. In 2017–2018, an integrated mapping strategy for onchocerciasis, lymphatic filariasis (LF), and loiasis, aimed at enabling safe ivermectin treatment decisions, was piloted in Gabon. Three ivermectin-naïve departments suspected to be hypo-endemic were selected and up to 100 adults per village across 30 villages in each of the three departments underwent testing for indicators of onchocerciasis, LF, and loiasis. An additional 67 communities in five adjoining departments were tested for loiasis to extend the prevalence and intensity predictions and possibly expand the boundaries of areas deemed safe for ivermectin treatment. Integrated testing in the three departments revealed within-department heterogeneity for all the three diseases, highlighting the value of a mapping approach that relies on cluster-based sampling rather than sentinel sites. These results suggest that safe mass treatment of onchocerciasis may be possible at the subdepartment level, even in departments where loiasis is present. Beyond valuable epidemiologic data, the study generated insight into the performance of various diagnostics and the feasibility of an integrated mapping approach utilizing new diagnostic and modeling tools. Further research should explore how programs can combine these diagnostic and risk prediction tools into a feasible programmatic strategy to enable safe treatment decisions where loiasis and onchocerciasis are co-endemic

Field evaluation of a schistosome circulating cathodic antigen rapid test kit at point-of-care for mapping of schistosomiasis endemic districts in The Gambia.

Studies in Sub Saharan Africa have shown that the Circulating Cathodic Antigen point-of-care-test (POC-CCA) is more accurate in the detections of S. mansoni than the microscopic Kato-Katz technique but less is known about the accuracy of this rapid test in detecting S. haematobium infections. This study was intended to evaluate the field accuracy of POC-CCA as a rapid test kit for schistosomiasis mapping in The Gambia.This prospective study was conducted in 4 regions in the country. Ten schools were randomly selected from each region, and a total of 2018 participants whose ages range from 7 to 14 years were enrolled in the study. Stool and urine samples were collected from each participant from May to June 2015, and tested for S. haematobium and S. mansoni infections in field and laboratory settings. The tests conducted included POC-CCA, double Kato-Katz slides, urine filtration and dipstick for hematuria.Of the 1954 participants that had complete data, the mean age of participants was 9.9 years. The prevalence of children infected with S. haematobium, using urine filtration technique was 10.1% (95% CI: 8.87-11.55). Central River Region had the highest level of urinary schistosomiasis with a prevalence of 28.0% (24.13-32.12).The lowest urinary schistosomiasis prevalence of 0.6% (0.12-1.86) was found in Lower River Region and North Bank Region had no cases of schistosomiasis detected. Only 5 participants were infected with S. mansoni. Using urine filtration as reference standard for the detection of S. haematobium, the sensitivity and specificity of POC-CCA was 47.7% and 75.8%. Whilst sensitivity and specificity of POC-CCA for detecting S. mansoni were 60.0% and 71.2% using double Kato-Katz as reference standard.This study showed lower sensitivity of POC-CCA in detecting S. haematobium. Therefore POC-CCA is less useful for rapid diagnosis of urinary schistosomiasis

Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis

The elimination of onchocerciasis through community-based Mass Drug Administration (MDA) of ivermectin (Mectizan) is hampered by co-endemicity of Loa loa, as individuals who are highly co-infected with Loa loa parasites can suffer serious and occasionally fatal neurological reactions from the drug. The test-and-not-treat strategy of testing all individuals participating in MDA has some operational constraints including the cost and limited availability of LoaScope diagnostic tools. As a result, a Loa loa Antibody (Ab) Rapid Test was developed to offer a complementary way of determining the prevalence of loiasis. We develop a joint geostatistical modelling framework for the analysis of Ab and Loascope data to delineate whether an area is safe for MDA. Our results support the use of a two-stage strategy, in which Ab testing is used to identify areas that, with acceptably high probability, are safe or unsafe for MDA, followed by Loascope testing in areas whose safety status is uncertain. This work therefore contributes to the global effort towards the elimination of onchocerciasis as a public health problem by potentially reducing the time and cost required to establish whether an area is safe for MDA

Circadian disruption, Per3, and human cytokine secretion

Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-1ra, IL-1-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may play a role. © The Author(s) 2009