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Background. The clinical presentation of Coronavirus disease 19 (COVID-19) varies from mild symptoms to severe illness including multiorgan dysfunction. Favipiravir is an antiviral agent which has been previously used for treatment of influenza and was recently approved for treatment of mild to moderate COVID-19 in India. Objective. The Objective of this study was to assess the role of Favipiravir and Dexamethasone in patients with COVID-19. Methods. A total of 17 patients were included in this observational study. The included patients were RT-PCR for SARS-Cov-2 positive with increased inflammatory markers. All patients received Antiviral therapy, Anticoagulation (Enoxaparin 0.4mg subcutaneous twice daily), Steroids (Dexamethasone 8mg daily for 5days and 4mg daily for 5 days). Viral clearance (time to RT-PCR negative), time to defervescence after antiviral therapy, time to become independent of Oxygen support was studied. Results. Fever, myalgias, dry cough and dyspnea were the commonest presentation of COVID-19. All of our patients had lymphopenia. In our study 11 (64.7%) patients had bilateral ground glass opacities on CT chest while 6 had consolidation in addition to ground glass opacities. In two patients, who required non-invasive ventilation, Favipiravir was stopped and these patients received Remdesivir for a total of 5 days. In patients who received Favipiravir only, the Median time to RT-PCR negative, defervescence and oxygen independence was 8,3 and 6 days respectively. Conclusion. Our observational study demonstrated improvement in the majority of patients with COVID-19 with use of Favipiravir. Additional studies are needed to compare the efficiency of Favipiravir with Remdesivir.

There is currently no single, easy-to-use, reliable indicator to assess whether a face has been washed with soap in the context of trachoma elimination. This study aimed to compare survey report, script-based pictorial recall and facial cleanliness indicators as alternatives to structured observation for measuring face washing behaviour. This method validation study was nested in the Stronger-SAFE trial, Oromia Region, Ethiopia. Structured observation was conducted in randomly selected households for three hours from dawn. The primary caregiver in each household participated in a survey to capture (self)-reported behaviour and/or script-based pictorial recall, a routine-based diary activity to covertly capture information on face washing behaviour of themself and any children aged 1-12. Children 4-12 years old directly participated in the survey and pictorial recall in a subset of households. The facial cleanliness of children aged 1-12 was assessed qualitatively and using the quantitative Personal Hygiene Assessment Tool (qPHAT). Prevalence estimates, sensitivity, specificity and predictive values were computed for each behavioural indicator with observation data as the gold standard. The appropriateness of script-based pictorial recall was assessed using baseline and 3-month follow-up data. Baseline data were collected from 204 households in 68 clusters. Survey estimates of face washing and face washing with soap among caregivers and children were 32% to 60% and 5% to 31% higher than observed behaviour, respectively. Face washing prevalence estimates from pictorial recall were lower than survey estimates and comparable with observations for some face washing with soap indicators (0.3% to 13% higher than observations). Specificity of pictorial recall indicators was high (85% to 99%), but the sensitivity was low (0% to 67%), resulting in a low positive predictive value for all indicators. Both qualitative facial cleanliness indicators and qPHAT scores were poorly correlated with observed face washing earlier that morning. Pictorial recall overestimated face washing with soap among both caregivers and children following intervention delivery but not at baseline. Survey (self)-reported data on face washing is highly inaccurate. Script-based pictorial recall does not correctly classify those who wash their face with soap, and is subject to differential bias following intervention exposure, and facial cleanliness is a poor indicator of recent face washing in settings where faces become rapidly dirty again after washing. Alternatives to structured observation cannot be recommended to monitor the effectiveness of face washing interventions in community settings. Trial Registration ISRCTN registry ISRCTN40760473, https://doi.org/10.1186/ISRCTN40760473., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Greenland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Extracorporeal membrane oxygenation (ECMO) is an increasingly used mode of critical care support for pediatric patients refractory to conventional therapy. We evaluated the characteristics, outcomes, and readmissions rates for pediatric ECMO in the United States., Methods: Data was extracted from the Nationwide Readmissions Database, a database designed to support national readmissions analyses, for patients aged 1-18 years undergoing ECMO between 2012-2018. Baseline demographics, comorbidities, and characteristics were identified using International Classification of Diseases codes., Results: Out of 897,117 index pediatric hospitalizations, 3706 patients underwent ECMO [median age 9 years (IQR 2,15); 51.6% males]. 2246 (60.6%) patients survived to hospital discharge, with a 30-day readmissions rate of 17% among survivors. Cardiac conditions associated with ECMO were congenital heart disease (25.3%), cardiogenic shock (23.6%), and congestive heart failure (16.2%). The common respiratory associations were sepsis (36.2%), pneumonia (35.6%), and asthma (15.4%). Patients who survived were more likely to have diagnoses of asthma, bronchiolitis, myocarditis, pneumonia, and sepsis. Acute kidney injury (51.5%), disseminated intravascular coagulation (22.5%), and surgical site bleeding (12.7%) were the commonly associated complications. The trend for yearly survival rates was not statistically significant (linear p-trend = 0.38)., Conclusions: Pediatric ECMO continues to be associated with notable mortality and complication rates. We did not observe a meaningful trend for the yearly survival rates over the study period, and over one-sixth of survivors were readmitted within 30-days. More research is needed to identify patients at high risk of mortality and readmissions, to help target resources more efficiently and improve survival., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Outcomes of cardiac arrest among patients who had cardiopulmonary resuscitation (CPR) in intensive care units (ICU) has limited data on the national level basis in the United States. We aimed to study the outcomes of ICU CPRs., Methods: Data from the national readmissions database (NRD) sample that constitutes 49.1% of the stratified sample of all hospitals in the United States were analyzed for ICU-related hospitalizations for the years 2016 to 2019. ICU CPR was defined by procedure codes., Results: A total of 4,610,154 ICU encounters were reported for the years 2016 to 2019 in the NRD. Of these patients, 426,729 (9.26%) had CPR procedure recorded during the hospital encounter (mean age 65 ± 17.81; female 42.4%). And 167,597 (39.29%) patients had CPR on the day of admission, of which 63.16% died; while 64,752 (15.18%) patients had CPR on the day of ICU admission, of which 72.85% died. And 36,002 (8.44%) had CPR among patients with length of stay 2 days, of which 73.34% died. A total of 1,222,799 (26.5%) admitted to ICU died, and patients who had ICU CPR had higher mortality, 291,391(68.3%). Higher complication rates were observed among ICU CPR patients, especially who died. Over the years from 2016 to 2019, ICU CPR rates increased from 8.18% (2016) to 8.66% (2019); p-trend = 0.001. The mortality rates among patients admitted to ICU increased from 22.1% (2016) to 24.1% (2019); p-trend = 0.005., Conclusion: The majority of ICU CPRs were done on the first day of ICU admission. The trend for ICU CPR was increasing. The mortality trend for overall ICU admissions has increased, which is concerning and would suggest further research to improve the high mortality rates in the CPR group., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Improving child health using health information technology (IT) requires a unique set of functionalities that are built into the electronic health record (EHR) and are used to support patient care. In this article, we review and discuss the milestones preceding the development of a new child health EHR standard and describe the salient features of this contemporary standard., Methods and Results: The Health Level Seven Pediatric Care Health IT Functional Profile (HL7 PCHIT FP) is an informative standard that encompasses the EHR functions required to care for patients less than 21 years of age in any clinical setting, developed to address the pediatric-specific functionality gaps in the EHR. It includes criteria that support communication between providers and all caregivers, inclusion of pediatric-specific vital signs and diagnosis, support for transition to adult care, and support for reporting and documentation of child abuse or neglect including communication with involved authorities. EHR functionalities for documentation and reporting of newborn screening tests with follow-up for abnormal results and functionality for children with special health care needs with support for identifying patients who may benefit from care coordination are also incorporated, in addition to school-based linkages enabling communication between the health care system and their school environment., Conclusion: The HL7 PCHIT FP is envisioned to be another vital step towards improving pediatric health by enhancing EHRs to address the unique health IT needs of children and their health providers. While the HL7 PCHIT FP is the most recently published standard on pediatric EHR systems, standards development is an iterative process, and recommendations for continuous refinement and additional functionalities for the next standards release are encouraged., Competing Interests: All the authors were members of the HL7 PCHIT workgroup that produced the PCHIT FP R1. F.Y is an organizational member of HL7 and co-chair of the HL7 EHR Work Group. T. B. and C.T. are employees of Drummond Group. T.M. is a Drummond contractor. Drummond has a for-profit Pediatric Health IT Certification Program., (Thieme. All rights reserved.)

Background: Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative potential, are not yet entirely known. This study investigates the key cardiac genes/ transcription factors (TFs) and signaling pathways to understand these important questions., Methods: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes., Results: The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2-5 and MSX2 contribute predominantly to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs), may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2-5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential., Conclusion: The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells., (© 2023. The Author(s).)

Background: Trachoma, the leading infectious cause of blindness, is caused by the bacterium Chlamydia trachomatis (Ct). Despite enormous disease control efforts and encouraging progress, trachoma remains a significant public health problem in 44 countries. Ethiopia has the greatest burden of trachoma worldwide, however, robust data exploring transmission risk factors and the association between socio-economic status is lacking from some regions. This is the first study to investigate these factors in this South-Eastern region of Oromia, Ethiopia., Methodology/principal Findings: A total of 1211 individuals were enrolled from 247 households in Shashemene Rural district in Oromia Region between 11th April and 25th June 2018, of whom 628 (51.9%) were female and 526 (43.4%) were children aged 1-9 years. Three standardised ophthalmic nurses examined each participant for the presence of active trachoma using the WHO simplified trachoma grading system. Conjunctival swab samples were collected from the upper tarsal conjunctiva of the left eye of each participant. Ct was detected using quantitative PCR. Risk factor data were collected through structured interviews and direct observations. Clinical signs of trachomatous inflammation-follicular among children aged 1-9 (TF1-9) were observed in at least one eye of 106/526 (20.2%) and trachomatous inflammation-intense among children aged 1-9 (TI1-9) were observed in at least one eye of 10/526 (1.9%). We detected Ct by PCR in 23 individuals, of whom 18 (78.3%) were in children aged 1-9 years. Among the 106 children aged 1-9 years with TF, 12 (11.3%) were Ct PCR positive and among 20 children aged 1-9 years with TI, 4 (20.0%) were Ct PCR positive. In a multivariable model, adjusting for household clustering, active trachoma was associated with younger age, the poorest households (aOR = 2.56, 95% CI 1.21-5.51), presence of flies on the face (aOR = 2.87, 95% CI 1.69-6.46), and ocular discharge (aOR = 1.89, 95% CI 1.03-3.24). Pre-school children face washing more than once a day had lower odds of having active trachoma (aOR = 0.59, 95% CI 0.19-0.84). The same was true for washing children's clothing at least once per week (aOR = 0.27, 95% CI 0.33-1.02)., Conclusion/significance: Younger age, personal hygiene in this age group (presence of ocular and nasal discharges, infrequent washing of faces and clothing) and fly-eye contacts are potential risk factors for trachoma in this setting, suggesting that hygiene interventions and environmental improvements are required to suppress transmission to ensure sustained reduction in disease burden Further studies are needed to evaluate these interventions for trachoma control and elimination. Trachoma remains a disease associated with lower socio-economic status, emphasising the need for continued implementation of control measures in addition to poverty reduction interventions in this region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shafi Abdurahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Cardiac arrest can complicate infective endocarditis (IE) and is associated with significant in-hospital complications and mortality rates. We report the characteristics, outcomes, and readmission rates for IE patients with cardiac arrest in the United States., Methods: We surveyed the Nationwide Readmission Database (NRD), a database designed to support national level readmission analyses, for patients admitted with IE and who had cardiac arrest during index admission between 2016 and 2019. Baseline demographics, comorbidities, surgical procedures, and outcomes were identified using their respective International Classification of Diseases (ICD) codes., Results: There were 663 index admissions (mean age 55.87 ± 17.21 years;34.2 % females) for IE with cardiac arrest in the study period, with an overall mortality rate of 55.3 %. Of these, 270 (40.7 %) had surgical procedures performed during the hospitalization encounter. In patients who had a surgical procedure, 72 (26.8 %) patients had in-hospital mortality while 293 (74.9 %) patients without surgical procedures had in-hospital mortality (p < 0.001). After coarsened matching for baseline characteristics, surgical valve procedures were less likely to be associated with mortality (OR = 0.09, 95%CI 0.04-0.24; p < 0.001). Among the 295 alive discharges associated with cardiac arrest, 76 (38.57 %) were readmitted within 30-days, with a mortality rate of 22 % noted for readmissions., Conclusion: Among IE patients who had cardiac arrest, surgical procedures subgroup had low mortality despite having higher complication rates. However, due to chances of bias more randomized trials are needed evaluate the hypothesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors have participated in the work and have reviewed and agree with the content of the article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

If facial hygiene practices vary seasonally this could have important implications for the design of interventions for trachoma control. This observational study was conducted to explore seasonal variation in hygiene behaviours in 9 households with at least one child aged 1-9 years-of-age in the West Arsi zone in rural Oromia, Ethiopia. Sixty-one household members were observed intensively over two days in the dry season (January), the rainy season (July) and during the harvest period (October) in 2018. Structured record forms were used to document household water availability and use. Daily water use per capita was very low in all seasons (3.1-4.2 litres). Around one third of water consumed in households in all seasons was associated with body washing. Soap was used during 44 of 677 (6%) of these observed occasions and half of all body washes (n = 340; 50%) included face washing. Overall, 95% of 58 individuals washed their faces at least once between 06:30h and 21:30h in the dry season (21% with soap), compared with 79% in the rainy season (2% with soap) (p = 0.013). Sixty-five percent of householders washed their faces during the harvest observation period (06:30h to 17:30h), none of whom used soap. Twenty-eight percent of 204 children aged 11 and under still had ocular or nasal discharge on their faces after washing. Seventy-three percent of those who washed their faces did so more than once in the dry season, compared with 33% in the rainy season (p<0.001). Face washing occurred throughout the day during the dry season, with a clear peak in the early morning and extra washes in the early evening. Face washing mainly took place in the early morning in the other two seasons. Genuine water scarcity in this area is likely to limit the impact of face washing interventions for trachoma control in the absence of water supply interventions. However, face washing was most common at the time of year when water is the hardest to come by, and seasonal differences in behaviour should be considered in any resulting intervention design., Competing Interests: The authors have declared that no competing interests exist.

Background: Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons., Methods: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes., Results: The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression., Conclusion: Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others., (© 2022. The Author(s).)

Literature regarding etiology and trends of incidence of major thoracic vein thrombosis in the United States is limited. To study the causes, complications, in-hospital mortality rate, and trend in the incidence of major thoracic vein thrombosis which could have led to superior vena cava syndrome (SVCS) between 2010 and 2018. Data from the nationwide emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments (ED) and in-patient sample in the United States were analyzed using diagnostic codes. A linear p-trend was used to assess the trends. Of the total 1082 million ED visits, 37,807 (3.5/100,000) (mean age 53.81 ± 18.07 years, 55% females) patients were recorded with major thoracic vein thrombosis in the ED encounters. Among these patients, 4070 (10.6%) patients had one or more cancers associated with thrombosis. Pacemaker/defibrillator-related thrombosis was recorded in 2820 (7.5%) patients, while intravascular catheter-induced thrombosis was recorded in 1755 (4.55%) patients. Half of the patients had associated complication of pulmonary embolism. A total of 59 (0.15%) patients died during these hospital encounters. The yearly trend for the thrombosis for every 100,000 ED encounters in the United States increased from 2.17/100,000 in 2010 to 5.98/100,000 in 2018 (liner p-trend < 0.001). Yearly trend for catheter/lead associated thrombosis was also up-trending (p-trend 0.015). SVCS is an uncommon medical emergency related to malignancy and indwelling venous devices. The increasing trend in SVCS incidence, predominantly catheter/lead induced, and the high rate of associated pulmonary embolism should prompt physicians to remain vigilant for appropriate evaluation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Literature regarding outcomes of cardiac arrest with associated NSTEMI is limited. We aim to study the predictors and survival outcomes of cardiac arrest patients presenting to the emergency department who were diagnosed with non-ST elevated myocardial infarction (NSTEMI)., Methods: Data from the nationwide emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments in the United States was analyzed for the cardiac arrest related visits from 2009-2018. Cardiac arrest was defined by the ICD codes., Results: Out of 3,235,555 cardiac arrests (mean age 64.0 ± 19.5 years, 40.7% females) there were 163,970 (5.1%) patients diagnosed with NSTEMI during the years 2009-2018. Among cardiac arrest patients, the survival for NSTEMI patients was higher than patients without NSTEMI (46.7% vs. 22.7%). These patients were more likely to be males and elderly. Among the predictors for NSTEMI cardiac arrests, hypertension (OR 1.12, p < 0.001), peripheral vascular disease (OR 1.16, p < 0.001), prior-coronary artery bypass graft (OR 1.20, p < 0.001) were the predominant ones. Cardiovascular interventions were more common in NSTEMI cardiac arrests and were associated with lower mortality rates (p < 0.001). However, trend for coronary interventions remained steady over study years. We observed an increase in prevalence of NSTEMI cardiac arrests with a worsening trend in survival from 2009-2018., Conclusions: NSTEMI was not uncommon in patients with cardiac arrest. NSTEMI cardiac arrest had a better prognosis than patients without NSTEMI. Cardiovascular interventions might have survival benefits. More research is required to identify NSTEMI in cardiac arrest patients and further evaluate the effect of cardiovascular interventions on survival., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Acute kidney injury (AKI) is frequent in hospitalized patients with critical illness and presents in up to one-quarter of patients with non-severe community-acquired pneumonia (CAP), resulting in increased short and long-term mortality. There is a paucity of literature from resource-limited settings regarding the incidence and risk factors for AKI in patients with CAP. In this study, we looked at the incidence and risk factors for AKI in patients hospitalized with CAP in a resource-limited setting Methods: This prospective observational study conducted over 1 year period included patients ≥ 18 years of age diagnosed with CAP admitted to a tertiary care center. The differences in baseline characteristics between hospitalized CAP patients with and without AKI; and risk factors for AKI and the need for renal replacement therapy (RRT) were analyzed using Chi-square test, t-test, Mann-Whitney U test, and logistic regression with p-value <0.05 considered statistically significant. Results: We observed 27.6 % (58/210) of patients had AKI in our study. Patients with AKI had significantly higher baseline comorbidities of chronic kidney disease (p=0.005) and coronary artery disease (p=0.032), and significantly higher uric acid (p=0.002), lower albumin (p=0.005), lower total protein (p=0.015), higher bilirubin (p=0.001), higher LDH (p=0.041), and higher CURB-65 score (p<0.001) in addition to elevated creatinine, BUN (p<0.001) compared to the no-AKI group. The patient group requiring RRT had significantly more males (p=0.019), with significantly higher phosphorus (p=0.038), lower ALT (p=0.022), and expectedly higher creatinine (p<0.001) and blood urea nitrogen (p=0.016). The adjusted logistic regression analysis revealed that patients with higher CURB-65 scores were at increased odds of undergoing RRT (OR 8.74, 95% CI 5.27 to 12.21, p=0.039). Conclusion: There is a high incidence of AKI in patients hospitalized for CAP in developing countries. Clinicians should be alert for the prevention and early detection of AKI in CAP patients., Competing Interests: Conflicts of Interest: None declared, (© 2021 Iran University of Medical Sciences.)

Background: Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing., Methods: Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells., Results: Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET - 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl - 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others.This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis., Conclusion: The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity.The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in 'switching' of vascular cells towards atherosclerosis., Competing Interests: Competing interestsThe author declares that he has no competing interests., (© The Author(s) 2020.)

Background: An accurate understanding of the geographical distributions of both soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale) and schistosomes (SCH; Schistosoma mansoni and S. haematobium) is pivotal to be able to effectively design and implement mass drug administration (MDA) programmes. The objective of this study was to provide up-to-date data on the distribution of both STH and SCH in Ethiopia to inform the design of the national control program and to be able to efficiently achieve the 75% MDA coverage target set by the WHO., Methods: Between 2013 and 2015, we assessed the distributions of STH and SCH infections in a nationwide survey covering 153,238 school-aged children (aged 5-15 years), from 625 woredas (districts), representing all nine Regional States and two City Administrations of Ethiopia. Nationwide disease maps were developed at the woreda level to enable recommendations on the design of the national MDA programme., Results: The prevalence of any STH infection across the study population was 21.7%, with A. lumbricoides (12.8%) being the most prevalent STH, followed by hookworms (7.6%) and T. trichiura (5.9%). The prevalence for any SCH was 4.0% in areas where both SCH species were evaluated. Schistosoma mansoni was the most prevalent SCH (3.5 vs 0.3%). STHs were more prevalent in southwest Ethiopia, whereas SCH was found mostly in the west and northeast of the country. The prevalence of moderate-to-heavy intensity infections was 2.0% for STHs and 1.6% for SCH. For STH, a total of 251 woredas were classified as moderately (n = 178) or highly endemic (n = 73), and therefore qualify for an annual and biannual MDA program, respectively. For SCH, 67 woredas were classified as endemic and 8 as highly endemic, and hence they require every two years and annual MDA programme, respectively., Conclusions: The results confirm that Ethiopia is endemic for both STHs and SCH, posing a significant public health problem. Following the WHO recommendations on mass drug administration, 18 and 14 million school-aged children are in need of MDA for STHs and SCH, respectively, based on the number of SACs that live on the eligible geographical areas.

Background: The presence of Chlamydia trachomatis (Ct) DNA at non-ocular sites suggests that these sites may represent plausible routes of Ct transmission in trachoma. However, qPCR cannot discriminate between DNA from viable and non-viable bacteria. Here we use a propodium monoazide based viability PCR to investigate how long Ct remains viable at non-ocular sites under laboratory-controlled conditions., Methods: Cultured Ct stocks (strain A2497) were diluted to final concentrations of 1000, 100, 10 and 1 omcB copies/μL and applied to plastic, woven mat, cotton cloth and pig skin. Swabs were then systemically collected from each surface and tested for the presence Ct DNA using qPCR. If Ct DNA was recovered, Ct viability was assessed over time by spiking multiple areas of the same surface type with the same final concentrations. Swabs were collected from each surface at 0, 2, 4, 6, 8 and 24 hours after spiking. Viability PCR was used to determine Ct viability at each timepoint., Results: We were able to detect Ct DNA on all surfaces except the woven mat. Total Ct DNA remained detectable and stable over 24 hours for all concentrations applied to plastic, pig skin and cotton cloth. The amount of viable Ct decreased over time. For plastic and skin surfaces, only those where concentrations of 100 or 1000 omcB copies/μL were applied still had viable loads detectable after 24 hours. Cotton cloth showed a more rapid decrease and only those where concentrations of 1000 omcB copies/μL were applied still had viable DNA detectable after 24 hours., Conclusion: Plastic, cotton cloth and skin may contribute to transmission of the Ct strains that cause trachoma, by acting as sites where reservoirs of bacteria are deposited and later collected and transferred mechanically into previously uninfected eyes., Competing Interests: The authors have declared that no competing interests exist.

Eye-to-eye transmission of Chlamydia trachomatis , the causative agent of trachoma, may be plausibly interrupted if faces are kept free of ocular and nasal discharge. Between April and June 2018, 83 children aged 1-9 years with active trachoma were recruited from 62 households and allocated to a face cleaning protocol: face washing with water, face washing with water and soap, or face wiping. Faces were examined for the presence of ocular and nasal discharge, and swabs were taken from faces and hands to test for C. trachomatis at baseline, immediately post protocol, and after 1, 2, and 4 hours (washing protocols). Washing with soap was more effective at removing ocular discharge than either washing with water (89% and 27% of discharge removed, respectively, P = 0.003) or wiping with a hand (42%, P = 0.013). The reduction in prevalence of ocular discharge was sustained for at least four hours. The prevalence of C. trachomatis on face swabs was reduced by all washing protocols. The importance of soap should not be overlooked during facial cleanliness promotion.

Background: Trachoma elimination efforts are hampered by limited understanding of Chlamydia trachomatis (Ct) transmission routes. Here we aimed to detect Ct DNA at non-ocular sites and on eye-seeking flies., Methods: A population-based household survey was conducted in Oromia Region, Ethiopia. Ocular and non-ocular (faces, hands, clothing, water containers and sleeping surfaces) swabs were collected from all individuals. Flies were caught from faces of children. Flies, ocular swabs and non-ocular swabs were tested for Ct by quantitative PCR., Results: In total, 1220 individuals in 247 households were assessed. Active trachoma (trachomatous inflammation-follicular) and ocular Ct were detected in 10% and 2% of all-ages, and 21% and 3% of 1-9-year-olds, respectively. Ct was detected in 12% (95% CI:8-15%) of tested non-ocular swabs from ocular-positive households, but in none of the non-ocular swabs from ocular-negative households. Ct was detected on 24% (95% CI:18-32%) of flies from ocular-positive households and 3% (95% CI:1-6%) of flies from ocular-negative households., Conclusion: Ct DNA was detected on hands, faces and clothing of individuals living in ocular-positive households suggesting that this might be a route of transmission within Ct infected households. In addition, we detected Ct on flies from ocular-positive households and occasionally in ocular-negative households suggesting that flies might be a vector for transmission within and between Ct infected and uninfected households. These potential transmission routes may need to be simultaneously addressed to suppress transmission., Competing Interests: The authors have declared that no competing interests exist.

Sample sizes in cluster surveys must be greater than those in surveys using simple random sampling in order to obtain similarly precise prevalence estimates, because results from subjects examined in the same cluster cannot be assumed to be independent. Therefore, a crucial aspect of cluster sampling is estimation of the intracluster correlation coefficient (ρ): the degree of relatedness of outcomes in a given cluster, defined as the proportion of total variance accounted for by between-cluster variation. In infectious disease epidemiology, this coefficient is related to transmission patterns and the natural history of infection; its value also depends on particulars of survey design. Estimation of ρ is often difficult due to the lack of comparable survey data with which to calculate summary estimates. Here we use a parametric bootstrap model to estimate ρ for the ocular clinical sign "trachomatous inflammation-follicular" (TF) among children aged 1-9 years within population-based trachoma prevalence surveys. We present results from a meta-regression analysis of data from 261 such surveys completed using standardized methods in Ethiopia, Mozambique, and Nigeria in 2012-2015. Consistent with the underlying theory, we found that ρ increased with increasing overall TF prevalence and smaller numbers of children examined per cluster. Estimates of ρ for TF were independently higher in Ethiopia than in the other countries., (World Health Organization 2020. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Purpose: The prevalence of trichiasis is higher in females and increases markedly with age. Surveys carried out in the daytime, particularly in developing countries, are prone to find older individuals and females at home at the time of the survey. Population-level trichiasis estimates should adjust sample proportions to reflect the demographic breakdown of the population, although the most accurate method of doing this is unclear., Methods: Having obtained data from 162 surveys carried out in Ethiopia as part of the Global Trachoma Mapping Project from 2012 to 2015, we used internal validation with both Brier and Logarithmic forecast scoring to test stratification models to identify those models with the highest predictive accuracy. Selection of partitions was undertaken by both simple random sampling (SRS) and cluster sampling (CS) over 8192 selections., Results: A total of 4529 (1.9%) cases of trichiasis were identified from 241,139 individuals aged ≥15 years from a total of 4210 kebeles and 122,090 households visited. Overall, the binning method using 5-year bands from age 15 to 69 years, with coarser binning in 20-year age-bands above this age, provided the best predictive accuracy, in both SRS and CS methodologies and for both the Brier and Logarithmic scoring rules., Conclusion: The greatest predictive accuracy for trichiasis estimates was found by adjusting for sex and in 5-year age-bands from the age of 15 to 69 years and in 20-year age-bands in those aged 70 years and greater. Trichiasis surveys attempting to make population-level inferences should use this method to optimise surgery backlog estimates.

In collaboration with the health ministries that we serve and other partners, we set out to complete the multiple-country Global Trachoma Mapping Project. To maximize the accuracy and reliability of its outputs, we needed in-built, practical mechanisms for quality assurance and quality control. This article describes how those mechanisms were created and deployed. Using expert opinion, computer simulation, working groups, field trials, progressively accumulated in-project experience, and external evaluations, we developed 1) criteria for where and where not to undertake population-based prevalence surveys for trachoma; 2) three iterations of a standardized training and certification system for field teams; 3) a customized Android phone-based data collection app; 4) comprehensive support systems; and 5) a secure end-to-end pipeline for data upload, storage, cleaning by objective data managers, analysis, health ministry review and approval, and online display. We are now supporting peer-reviewed publication. Our experience shows that it is possible to quality control and quality assure prevalence surveys in such a way as to maximize comparability of prevalence estimates between countries and permit high-speed, high-fidelity data processing and storage, while protecting the interests of health ministries.

Background: The goal of the global lymphatic filariasis (LF) program is to eliminate the disease as a public health problem by the year 2020. The WHO mapping protocol that is used to identify endemic areas in need of mass drug administration (MDA) uses convenience-based sampling. This rapid mapping has allowed the global program to dramatically scale up treatment, but as the program approaches its elimination goal, it is important to ensure that all endemic areas have been identified and have received MDA. In low transmission settings, the WHO mapping protocol for LF mapping has several limitations. To correctly identify the LF endemicity of woredas, a new confirmatory mapping tool was developed to test older school children for circulating filarial antigen (CFA) in settings where it is uncertain. Ethiopia is the first country to implement this new tool. In this paper, we present the Ethiopian experience of implementing the new confirmatory mapping tool and discuss the implications of the results for the LF program in Ethiopia and globally., Methods: Confirmatory LF mapping was conducted in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of previous mapping for LF using the current WHO protocol indicated that LF endemicity was uncertain. Within each woreda schools were selected using either cluster or systematic sampling. From selected schools, a total of 18,254 children were tested for circulating filarial antigen (CFA) using the immuno-chromatographic test (ICT)., Results: Of the 18,254 children in 45 woredas who participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive. According to the confirmatory mapping threshold, which is ≥2% CFA in children 9-14 years of age, only 3 woredas out of the total 45 had more CFA positive results than the threshold and thus were confirmed to be endemic; the remaining 42 woredas were declared non-endemic. These results drastically decreased the estimated total population living in LF-endemic woredas in Ethiopia and in need of MDA by 49.1%, from 11,580,010 to 5,893,309., Conclusion: This study demonstrated that the new confirmatory mapping tool for LF can benefit national LF programs by generating information that not only can confirm where LF is endemic, but also can save time and resources by preventing MDA where there is no evidence of ongoing LF transmission.

Introduction: The optimal fluid therapy in children with DKA is a matter of debate, especially if we take into account its association with cerebral edema, the most important complication. Hypertonic Saline Solution is used in the treatment of cerebral edema, and also has been used for volume resuscitation in children with shock., Aim of Study: To compare the effects of 3% saline and 0.9% saline solutions on changes in vital parameters, sodium and chloride levels, lactate and pH; time needed for the correction of hyperglycemia; time needed for the control of ketoacidosis and incidence of cerebral edema., Methods: Open-label prospective RCT in which 40 children with moderate to severe DKA were randomized to receive either 3% saline or 0.9% saline as initial fluid therapy., Results: There was no significant difference between the two groups in the clinical vital parameters, time for the correction of hyperglycemia and the resolution of acidosis. Patients in the 3% saline group had a higher increase in sodium and chloride from baseline compared to the 0.9% saline group. The acidemia was noted to worsen in both groups after the initiation of fluid therapy, which was not associated with clinical deterioration. The frequency of cerebral edema was similar in both groups., Conclusions: Both 0.9% saline and 3% saline were equally effective as initial fluid in children with DKA with respect to hemodynamic improvement, the resolution of acidosis and the correction of hyperglycemia, but the use of 3% saline solution did not preclude the development of cerebral edema and has the potential to cause hypernatremia, hyperchloremia and hyperchloremic metabolic acidosis., (© Polish Society for Pediatric Endocrinology and Diabetology.)

Background: In Ethiopia there is no complete registration system to measure disease burden and risk factors accurately. In this study, the 2015 global burden of diseases, injuries and risk factors (GBD) data were used to analyse the incidence, prevalence and mortality rates of malaria in Ethiopia over the last 25 years., Methods: GBD 2015 used verbal autopsy surveys, reports, and published scientific articles to estimate the burden of malaria in Ethiopia. Age and gender-specific causes of death for malaria were estimated using cause of death ensemble modelling., Results: The number of new cases of malaria declined from 2.8 million [95% uncertainty interval (UI) 1.4-4.5 million] in 1990 to 621,345 (95% UI 462,230-797,442) in 2015. Malaria caused an estimated 30,323 deaths (95% UI 11,533.3-61,215.3) in 1990 and 1561 deaths (95% UI 752.8-2660.5) in 2015, a 94.8% reduction over the 25 years. Age-standardized mortality rate of malaria has declined by 96.5% between 1990 and 2015 with an annual rate of change of 13.4%. Age-standardized malaria incidence rate among all ages and gender declined by 88.7% between 1990 and 2015. The number of disability-adjusted life years lost (DALY) due to malaria decreased from 2.2 million (95% UI 0.76-4.7 million) in 1990 to 0.18 million (95% UI 0.12-0.26 million) in 2015, with a total reduction 91.7%. Similarly, age-standardized DALY rate declined by 94.8% during the same period., Conclusions: Ethiopia has achieved a 50% reduction target of malaria of the millennium development goals. The country should strengthen its malaria control and treatment strategies to achieve the sustainable development goals.

Introduction: Neglected tropical diseases (NTDs) are important public health problems in Ethiopia. In 2013, the Federal Ministry of Health (FMOH) has launched a national NTD master plan to eliminate major NTDs of public health importance by 2020. Benchmarking the current status of NTDs in the country is important to monitor and evaluate the progress in the implementation of interventions and their impacts. Therefore, this study aims to assess the trends of mortality and Disability-adjusted Life-Years (DALY) for the priority NTDs over the last 25 years., Methods: We used the Global Burden of Disease (GBD) 2015 estimates for this study. The GBD 2015 data source for cause of death and DALY estimation included verbal autopsy (VA), Demographic and Health Surveys (DHS), and other disease specific surveys, Ministry of Health reports submitted to United Nations (UN) agencies and published scientific articles. Cause of Death Ensemble modeling (CODEm) and/or natural history models were used to estimate NTDs mortality rates. DALY were estimated as the sum of Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability (YLD)., Results: All NTDs caused an estimated of 6,293 deaths (95% uncertainty interval (UI): 3699-10,080) in 1990 and 3,593 deaths (95% UI: 2051 - 6178) in 2015, a 43% reduction over the 25 years. Age-standardized mortality rates due to schistosomiasis, STH and leshmaniasis have declined by 91.3%, 73.5% and 21.6% respectively between 1990 to 2015. The number of DALYs due to all NTDs has declined from 814.4 thousand (95% UI: 548 thousand-1.2million) in 1990 to 579.5 thousand (95%UI: 309.4 thousand-1.3 million) in 2015. Age-standardized DALY rates due to all NTDs declined by 30.7%, from 17.6 per 1000(95%UI: 12.5-26.5) in 1990 to 12.2 per 1000(95%UI: 6.5 - 27.4) in 2015. Age-standardized DALY rate for trachoma declined from 92.7 per 100,000(95% UI: 63.2 - 128.4) in 1990 to 41.2 per 100,000(95%UI: 27.4-59.2) in 2015, a 55.6% reduction between 1990 and 2015. Age-standardized DALY rates for onchocerciasis, schistosomiasis and lymphiaticfilariasis decreased by 66.2%, 29.4% and 12.5% respectively between 1990 and 2015. DALY rate for ascariasis fell by 56.8% over the past 25 years., Conclusions: Ethiopia has made a remarkable progress in reducing the DALY rates for most of the NTDs over the last 25 years. The rapid scale of interventions and broader system strengthening may have a lasting impact on achieving the 2020 goal of elimination of most of NTDs. Ethiopia should strengthen the coverage of integrated interventions of NTD through proper coordination with other health programs and sectors and community participation to eliminate NTDs by 2020.

Purpose: To complete the baseline trachoma map in Oromia, Ethiopia, by determining prevalences of trichiasis and trachomatous inflammation - follicular (TF) at evaluation unit (EU) level, covering all districts (woredas) without current prevalence data or active control programs, and to identify factors associated with disease., Methods: Using standardized methodologies and training developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from December 2012 to July 2014., Results: Teams visited 46,244 households in 2037 clusters from 252 woredas (79 EUs). A total of 127,357 individuals were examined. The overall age- and sex-adjusted prevalence of trichiasis in adults was 0.82% (95% confidence interval, CI, 0.70-0.94%), with 72 EUs covering 240 woredas having trichiasis prevalences above the elimination threshold of 0.2% in those aged ≥15 years. The overall age-adjusted TF prevalence in 1-9-year-olds was 23.4%, with 56 EUs covering 218 woredas shown to need implementation of the A, F and E components of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement) for 3 years before impact surveys. Younger age, female sex, increased time to the main source of water for face-washing, household use of open defecation, low mean precipitation, low mean annual temperature, and lower altitude, were independently associated with TF in children. The 232 woredas in 64 EUs in which TF prevalence was ≥5% require implementation of the F and E components of the SAFE strategy., Conclusion: Both active trachoma and trichiasis are highly prevalent in much of Oromia, constituting a significant public health problem for the region.

Background: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD., Methods: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease. This research explores inverse relationship between AD and cancer, also investigates other factors behind AD using several already published research literature to find the etiology of AD., Results: Cancer and Alzheimer's disease have inverse relationship in many aspects such as P53, estrogen, neurotrophins and growth factors, growth and proliferation, cAMP, EGFR, Bcl-2, apoptosis pathways, IGF-1, HSV, TDP-43, APOE variants, notch signals and presenilins, NCAM, TNF alpha, PI3K/AKT/MTOR pathway, telomerase, ROS, ACE levels. AD occurs when brain neurons have weakened growth, cell survival responses, maintenance mechanisms, weakened anti-stress responses such as Vimentin, Carbonic anhydrases, HSPs, SAPK. In cancer, these responses are upregulated and maintained. Evolutionarily conserved responses and maintenance mechanisms such as FOXO are impaired in AD. Countermeasures or compensatory mechanisms by AD affected neurons such as Tau, Beta Amyloid, S100, are last attempts for survival which may be protective for certain time, or can speed up AD in Alzheimer's microenvironment via C-ABL activation, GSK3, neuro-inflammation., Conclusions: Alzheimer's disease and Cancer have inverse relationship; many factors that are upregulated in any cancer to sustain growth and survival are downregulated in Alzheimer's disease contributing to neuro-degeneration. When aged neurons or genetically susceptible neurons have weakened growth, cell survival and anti-stress responses, age related gene expression changes, altered regulation of cell death and maintenance mechanisms, they contribute to Alzheimer's disease. Countermeasures by AD neurons such as Beta Amyloid Plaques, NFTs, S100, are last attempts for survival and this provides neuroprotection for certain time and ultimately may become pathological and speed up AD. This study may contribute in developing new potential diagnostic tests, interventions and treatments.

In June 2013, at the launch of its National Neglected Tropical Disease (NTD) Master Plan, the Ethiopian government pledged to achieve WHO NTD elimination and control targets by 2020. With an estimated 80 million people living in areas where one or more NTDs are endemic, this goal presented an enormous challenge for the Federal Ministry of Health. However, as of September 2015, the Federal Ministry of Health has managed to mobilize support to implement mass drug administration in 84% of the trachoma endemic districts and 100% of the endemic districts for onchocerciasis, lymphatic filariasis, soil-transmitted helminthes and schistosomiasis. The national program still is facing large gaps in its podoconiosis and leishmaniasis programs, and it faces significant other challenges to stay on track for 2020 targets. However, this unprecedented scale-up in support was achieved through significant government investment in NTD interventions and creative coordination between donors and implementing partners, which may provide valuable lessons for other national NTD programs trying to achieve nationwide coverage., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated., Methodology/principal Finding: A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016., Conclusions: We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale.

Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease.

Background: Podoconiosis is one of the major causes of lymphoedema in the tropics. Nonetheless, currently there are no endemicity classifications or elimination targets to monitor the effects of interventions. This study aimed at establishing case definitions and indicators that can be used to assess endemicity, elimination and clinical outcomes of podoconiosis., Methods: This paper describes the result of a Delphi technique used among 28 experts. A questionnaire outlining possible case definitions, endemicity classifications, elimination targets and clinical outcomes was developed. The questionnaire was distributed to experts working on podoconiosis and other neglected tropical diseases in two rounds. The experts rated the importance of case definitions, endemic classifications, elimination targets and the clinical outcome measures. Median and mode were used to describe the central tendency of expert responses. The coefficient of variation was used to describe the dispersals of expert responses., Results: Consensus on definitions and indicators for assessing endemicity, elimination and clinical outcomes of podoconiosis directed at policy makers and health workers was achieved following the two rounds of Delphi approach among the experts., Conclusions: Based on the two Delphi rounds we discuss potential indicators and endemicity classification of this disabling disease, and the ongoing challenges to its elimination in countries with the highest prevalence. Consensus will help to increase effectiveness of podoconiosis elimination efforts and ensure comparability of outcome data., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues., Methodology: Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008-2010. The integrated mapping used woreda (district) health offices' reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence., Principal Findings: Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2-51.7) million people (i.e. 43.8%; 95% CI: 25.3-64.8% of Ethiopia's national population) lived in areas environmentally suitable for the occurrence of podoconiosis., Conclusions: Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale.

Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1-6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9-4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, and being semiskilled or unemployed were significantly associated with increased risk of podoconiosis. Attending formal education and living in a house with a covered floor were associated with decreased risk of podoconiosis. Podoconiosis exhibits marked geographical variation across Ethiopia, with variation in risk associated with variation in rainfall, enhanced vegetation index, and altitude., (© The American Society of Tropical Medicine and Hygiene.)

Background: There is considerable interest in determining whether mass drug administration (MDA) with ivermectin for onchocerciasis control will eliminate coendemic lymphatic filariasis (LF). The objective of this study was to determine the prevalence of LF microfilaremia in onchocerciasis endemic districts that had received 7 years of MDA with ivermectin., Method: Three villages with a 2010 LF circulating antigenaemia prevalence (determined in a mapping exercise using immunochromatography tests) ranging from 23 to 56% were surveyed for the presence of Wuchereria bancrofti microfilaria (mf) in 2012. These villages had been treated with ivermectin MDA for onchocerciasis with reported total population coverage of ≥65%. A total of 774 residents aged 2 years and above, of both genders, provided 60 μl nocturnal blood samples between 10 pm and 2 am. Standard thick smears were prepared and examined microscopically after Giemsa staining for the presence of W. bancrofti mf., Results: The mean mf prevalence was 4.7% (village range 1.1-11.0%). The mean mf density was 9.8 mf/60 μl (village range 9-13.1) among the positive individuals. Children in the 2-4-year-old and 5-9-year-old age groups were infected suggesting transmission occurred during the MDA period. A village level review of MDA treatment coverage records showed an average total population coverage of 66.4% over a 7-year period, but with a considerable range of annual coverage (43.0-89.9%). In addition, village level treatment coverage data were missing from the village with the highest mf prevalence (11%) for 2 of the 7 years., Conclusion: 7 years of annual mass treatment with ivermectin monotherapy for onchocerciasis did not interrupt LF transmission. In expanding the onchocerciasis ivermectin MDA programme to include LF, albendazole should be added and treatment coverage improved.

Background: Smear-negative and extra-pulmonary tuberculosis (TB) comprise two thirds of TB cases reported in Ethiopia. Neither treatment outcomes nor underlying associated factors are routinely reported for these cases., Objective: To assess treatment outcomes and associated risk factors of smear-negative and extra-pulmonary TB in comparison with smear-positive cases., Design: Record review of all TB cases registered in 14 randomly selected public and private health facilities in Addis Ababa, Ethiopia, over a 1-year period., Results: Percentages of smear-negative and extra-pulmonary TB were independent of human immunodeficiency virus (HIV) status, and were not evenly distributed among health facilities. Extra-pulmonary TB was overrepresented in the private sector, and smear-negative TB was more frequent in health clinics than in hospitals. Outcomes reported by clinics were more favourable than those of the hospitals; no differences were observed when comparing public and private health facilities. Only 54% of the TB registers were complete; missing information correlated with unfavourable outcomes. Younger age, but not sex or HIV status, was associated with favourable outcomes., Conclusion: The uneven distribution of smear-negative and extra-pulmonary TB among different health facilities requires further study and may provide important insight into diagnosis and care of these patients. Incomplete TB register information may be an underappreciated factor contributing to unfavourable outcomes.

Background: The World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of neglected tropical diseases (NTDs). Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt., Methods: Integrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A clinical algorithm was used to reliably diagnose podoconiosis by excluding other potential causes of lymphoedema of the lower limb., Results: A total of 8110 individuals with leg swelling were interviewed and underwent physical examination. Smartphones linked to a central database were used to collect data, which facilitated real-time data entry and reduced costs compared to traditional paper-based data collection approach; their inbuilt Geographic Positioning System (GPS) function enabled simultaneous capture of geographical coordinates. The integrated approach led to efficient use of resources and rapid mapping of an enormous geographical area and was well received by survey staff and collaborators. Mobile based technology can be used for such large scale studies in resource constrained settings such as Ethiopia, with minimal challenges., Conclusions: This was the first integrated mapping of podoconiosis and LF globally. Integrated mapping of podoconiosis and LF is feasible and, if properly planned, can be quickly achieved at nationwide scale.