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Structural differences along the long-axis of the hippocampus have long been believed to underlie meaningful functional differences, such as the granularity of information processing. Recent findings show that data-driven parcellations of the hippocampus sub-divide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where subjects were trained to virtually navigate a novel neighborhood in a Google Street View-like environment over a two-week period. Subjects were scanned while navigating routes early in training and at the end of their two-week training. Using the 10-cluster map as the ideal template, we find that subjects who eventually learn the neighborhood well have hippocampal cluster-maps consistent with the ideal—even on their second day of learning—and their cluster mappings do not change over the two week training period. However, subjects who eventually learn the neighborhood poorly begin with hippocampal cluster-maps inconsistent with the ideal, though their cluster mappings become more stereotypical by the end of the two week training. Interestingly this improvement seems to be route specific as even after some early improvement, when a new route is navigated participants’ hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure, and instead is driven by a combination of anatomy, task, and importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral-axes.

We aimed to estimate the prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds and trachomatous trichiasis (TT) unknown to the health system in ≥15-year-olds in Benishangul Gumuz (BGZ) region, Ethiopia. This will help to assess progress towards the elimination of trachoma as a public health problem and determine the need for future interventions against trachoma in the region.Cross-sectional population-based trachoma prevalence surveys were conducted in four evaluation units (EUs) of BGZ using World Health Organization-recommended survey methodologies. Individuals were examined for clinical signs of trachoma. Household access to water, sanitation and hygiene facilities (WaSH) was assessed.A total of 11,778 people aged ≥1 year were examined. The prevalence of TF in 1-9-year-olds was5% in three EUs and ≥5% in one EU. The prevalence of TT unknown to the health system in people aged ≥15-years was ≥0.2% in all four EUs. The proportion of households with an improved drinking water source within a 30-minute round-trip ranged from 27-60%. The proportion of households with an improved latrine ranged from1-6%.Surgical interventions for TT are required in all EUs in BGZ. One annual round of mass drug administration (MDA) of azithromycin is required in one EU before resurvey to reassess progress in lowering TF prevalence below the WHO elimination threshold of 5% in 1-9-year-olds. MDA should be stopped in the other three EUs and trachoma surveillance surveys should be conducted at least 24 months after the surveys described here. Ongoing strengthening of WaSH infrastructure may help sustain the low prevalence of trachoma.

Background Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

Background Ethiopia aims to eliminate lymphatic filariasis by 2020, through a dual approach of mass drug administration to interrupt transmission and morbidity control which includes making hydrocele surgery available in all endemic areas. Locating patients requiring surgery, providing high quality surgeries, and following up patients are all formidable challenges for many resource-challenged or difficult-to-reach communities. To date, hydrocele surgery in Ethiopia has only occurred when a patient has the knowledge, time and resources to travel to regional hospitals. Ethiopia tested the novel approach of using a surgical camp, defined as mobilizing, transporting, providing surgery at a static site, and following up of a large cohort of hydrocele patients within a hospital’s catchment area, to address delays in seeking and receiving care. Methodology and results Health extension workers mobilized 252 patients with scrotal swelling from a list of 385 suspected hydrocele cases from seven endemic districts in the region of Beneshangul-Gumuz. Clinical health workers and surgeons confirmed 119 as eligible for surgery. Of 70 additional patients who self-referred, 56 were eligible for surgery. Over a two-week period at a regional hospital, 175 hydrocele excision surgeries were conducted. After discharge three days after surgery, trained clinical health workers followed up with the patients on Day 5, Day 8, Day 14 and 1st-month benchmarks with a randomized follow-up of a selection of patients conducted at 9–12 months. There were no post-operative complications upon discharge at Day 3 and 22, while minor complications occurred (12.6%) between Day 3 and one month. The 9–12 month follow-up found patients self-reported an improvement in quality of life, health and economic status. Conclusion A hydrocele surgery camp was effective at providing a large number of quality surgeries in a short time. Using peripheral health workers to mobilize and follow up patients helped address delays in seeking and receiving quality care. Mainstreaming patient mobilization and follow-up into a community health system could be effective in other countries. The camp’s results also influenced two regions in Ethiopia to change their policies in order to offer free hydrocele surgery (including patient transport, consultation, surgery, diagnostic tests and necessary medications)., Author summary Hydrocele is a type of scrotal swelling caused by lymphatic filariasis and requires surgery to treat, which can be challenging to address in many endemic countries. Locating and referring patients, providing high quality surgical intervention, and creating a patient follow-up mechanism are all formidable aspects in communities that are often resource challenged and difficult to reach. We explored if the use of a surgical camp setting would be an appropriate intervention to adequately treat a large number of hydrocele patients over a short period, decreasing delays in seeking, reaching and receiving quality surgery for hydrocele. We analyzed each step required to hold the camp including some novel innovations surrounding patient mobilization, referral, and post-surgical quality assurance. The camp was effective at providing a large number of quality surgeries in a short time, with patients self-reporting improvements in quality of life, economic and health status after surgery. The findings from the study may prove useful for countries seeking to implement similar interventions.

The 2021–2030 Neglected Tropical Diseases road map calls for intensified cross-cutting approaches. By moving away from vertical programming, the integration of platforms and intervention delivery aims to improve efficiency, cost-effectiveness and programme coverage. Drawing on the direct experiences of the authors, this article outlines key elements for successful integrated surveys, the challenges encountered, as well as future opportunities and threats to such surveys. There are multiple advantages. Careful planning should ensure that integration does not result in a process that is less efficient, more expensive or that generates data driving less reliable decisions than conducting multiple disease-specific surveys.

While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes., Brady et al. demonstrate that spike protein-targeting antibodies reduce SARS-CoV-2 biodistribution. This highlights potential avenues for vaccine development.

Background SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. Main body We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. Conclusions While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.

Trachoma programs use annual antibiotic mass drug administration (MDA) in evaluation units (EUs) that generally encompass 100,000–250,000 people. After one, three, or five MDA rounds, programs undertake impact surveys. Where impact survey prevalence of trachomatous inflammation—follicular (TF) in 1- to 9-year-olds is ≥ 5%, ≥ 1 additional MDA rounds are recommended before resurvey. Impact survey costs, and the proportion of impact surveys returning TF prevalence ≥ 5% (the failure rate or, less pejoratively, the MDA continuation rate), therefore influence the cost of eliminating trachoma. We modeled, for illustrative EU sizes, the financial cost of undertaking MDA with and without conducting impact surveys. As an example, we retrospectively assessed how conducting impact surveys affected costs in the United Republic of Tanzania for 2017–2018. For EUs containing 100,000 people, the median (interquartile range) cost of continuing MDA without doing impact surveys is USD 28,957 (17,581–36,197) per EU per year, whereas continuing MDA solely where indicated by impact survey results costs USD 17,564 (12,158–21,694). If the mean EU population is 100,000, then continuing MDA without impact surveys becomes advantageous in financial cost terms only when the continuation rate exceeds 71%. For the United Republic of Tanzania in 2017–2018, doing impact surveys saved enough money to provide MDA for > 1,000,000 people. Although trachoma impact surveys have a nontrivial cost, they generally save money, providing EUs have > 50,000 inhabitants, the continuation rate is not excessive, and they generate reliable data. If all EUs pass their impact surveys, then we have waited too long to do them.

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites—referred to as pre-transmission assessment surveys (pre-TAS)—in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS., Author summary Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five rounds of mass drug administration (MDA) and being able to demonstrate low prevalence in several subsequent assessments. LF elimination programs implement sentinel and spot-check site assessments, called pre-TAS, to determine whether districts are eligible to implement more rigorous population-based surveys to determine whether MDA can be stopped or if further rounds are required. Reasons for failing pre-TAS are not well understood and have not previously been examined with data compiled from multiple countries. For this analysis, we analyzed data from routine USAID and WHO reports from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. In a model that included multiple variables, high baseline prevalence and lower elevation were significant. In models comparing only one variable to the outcome, the following were statistically significantly associated with failure: higher baseline prevalence at or above 5% or 10%, use of the FTS, primary vector of Culex, treatment with diethylcarbamazine-albendazole, lower elevation, higher population density, higher Enhanced Vegetation Index, higher annual rainfall, and six or more rounds of mass drug administration. These results can help national programs plan MDA more effectively, e.g., by focusing resources on areas with higher baseline prevalence and/or lower elevation.

Author(s): Hiep, Nguyen Xuan; Ngondi, Jeremiah M; Anh, Vu Tuan; Dat, Tran Minh; An, Tran Van; Dung, Nguyen Chi; Thang, Nguyen Duy; Chu, Brian K; Willis, Rebecca; Bakhtiari, Ana; Pavluck, Alexandre L; Johnson, James; Sidwell, Joshua; Brady, Molly; Henry, Rob; Mosher, Aryc; Porco, Travis C; Lietman, Thomas M; Rotondo, Lisa A; Lewallen, Susan; Courtright, Paul; Solomon, Anthony W; Global Trachoma Mapping Project | Abstract: PurposeFollowing interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis.MethodsA population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9nyears and adults aged ≥50nyears) were examined for trachoma.ResultsA total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Ha Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50nyears, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50nyears, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages.ConclusionFindings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Ha Giang Province, further investigations will be undertaken.

Background Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia. Methods The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70% epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery. Results Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1% of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011–2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients had been trained on self-management and all hydrocele patients had been offered free surgery. Conclusions Due to the success of the MDA and the development of health center capacity for patient care, along with benefits gained from socioeconomic improvements and other interventions against vector-borne diseases and NTDs, Cambodia was validated by the World Health Organization as achieving LF elimination as a public health problem in 2016. Electronic supplementary material The online version of this article (10.1186/s40249-018-0394-7) contains supplementary material, which is available to authorized users.

We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligées and collected data for 9 of 55 communes participating in the May 2008–April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligées Program partnered with IMA World Health and Hôpital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S. $0.64 per person, which included the cost of donated drugs, and at a cost of U.S. $0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S. $2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale.

Background The World Health Organization (WHO) in collaboration with partners is developing a toolkit of resources to guide lymphatic filariasis (LF) morbidity management and disability prevention (MMDP) implementation and evaluation. Direct health facility inspection is the preferred method for documenting the readiness of a country programme to provide quality lymphoedema management services, one of the three MMDP criteria used to demonstrate the elimination of LF as a public health problem. Methodology/Principal findings As component of tool development, a Delphi consultation was implemented to gain consensus on six proposed domains and fourteen proposed tracer indicators to measure national programme readiness to provide quality health facility-based lymphoedema management services. A seven-point Likert-type scale was used to rank the importance of proposed domains and tracer indicators. Consensus for inclusion of the indicator was defined a priori as 70% or more of respondents ranking the proposed indicator in the top three tiers (5–7). Purposive sampling was used to select 43 representative experts including country representatives, programme implementers, and technical experts. A 55.8% response rate (n = 24) was achieved for the survey. Analysis of the responses demonstrated that consensus for inclusion had been reached for all proposed domains including trained staff (mean = 6.9, standard deviation (SD) = 0.34), case management and education materials (mean = 6.1, SD = 0.65), water infrastructure (mean = 6.3, SD = 0.81), medicines and commodities (mean = 6.3, SD = 0.69), patient tracking system (mean = 6.3, SD = 0.85), and staff knowledge (mean = 6.5, SD = 0.66). Significance The Delphi consultation provided an efficient and structured method for gaining consensus among lymphatic filariasis experts around key lymphoedema management quality indicators. The results from this analysis were used to refine the indicators included within the direct inspection protocol tool to ensure its ability to assess health facility readiness to provide quality lymphoedema management services., Author summary Prior to this assessment, there was a need for clearly defined, measurable indicators for global lymphoedema management programmes to use to evaluate their lymphoedema morbidity management and disability prevention services. The results presented in this report outline a framework for indicators to assess healthcare facility-based readiness to provide quality lymphoedema management services. We describe our use of the Delphi methodology to obtain consensus on programme evaluation metrics as a model for elimination or control metrics and targets. The quality indicators developed from this Delphi consultation will be used to improve the direct inspection protocol tool that can be used to assess health facility readiness to provide quality lymphoedema management services LF endemic countries.

Background To reach the global goal of elimination of lymphatic filariasis as a public health problem by 2020, national programs will have to implement a series of transmission assessment surveys (TAS) to determine prevalence of the disease by evaluation unit. It is expected that 4,671 surveys will be required by 2020. Planning in advance for the costs associated with these surveys is essential to ensure that the required resources are available for this essential program activity. Methodology and Findings Retrospective cost data was collected from reports from 13 countries which implemented a total of 105 TAS surveys following a standardized World Health Organization (WHO) protocol between 2012 and 2014. The median cost per survey was $21,170 (including the costs for rapid diagnostic tests [RDTs]) and $9,540 excluding those costs. Median cost per cluster sampled (without RDT costs) was $101. Analysis of costs (excluding RDTs) by category showed that the main cost drivers were personnel and travel. Conclusion Transmission assessment surveys are critical to collect evidence to validate elimination of LF as a public health problem. National programs and donors can use the costing results to adequately plan and forecast the resources required to undertake the necessary activities to conduct high-quality transmission assessment surveys., Author Summary As national programs are nearing elimination of lymphatic filariasis as a public health problem, questions have been raised about the cost of collecting the data necessary for documenting validation of elimination. A series of standardized population-based surveys is necessary to determine prevalence of infection in endemic areas. The authors retrospectively collected data on the costs of these surveys from 13 countries to determine median cost per survey and per cluster sampled. Costs were found to be comparable with other neglected tropical disease surveys. The major cost drivers were personnel and travel for supporting collection of data in the field. National programs and donors can use these results to plan and advocate more effectively for sufficient resources to support validation of elimination.

Background Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (≥5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (

The integration of preventive chemotherapy programs (PCPs) targeting multiple neglected tropical diseases (NTDs) with similar strategic approaches offers opportunities for enhanced cost-effectiveness. To estimate the potential cost savings and health outcomes of integrated programs, the data available for five NTDs (lymphatic filariasis, onchocerciasis, intestinal helminthiasis, schistosomiasis and trachoma) can be used to define eligible target populations, the probable overlap of at-risk populations, and the cost per person treated in stand-alone and integrated programs. If all targets for 2006 in sub-Saharan Africa are met, then savings of 26-47% can be projected from such integration (a cost of US dollar 58-81 million versus dollar 110 million for stand-alone PCPs). These first estimates can be refined as empirical data become available from integrated PCPs in the future.

Neglected tropical diseases (NTDs) cause significant morbidity and mortality worldwide and impose a large economic burden on endemic countries [1]. In 2006, the United States Agency for International Development (USAID) founded the NTD Control Program to target five NTDs in African, Asian, and Latin American countries, namely, lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), and trachoma; the three targeted STH infections are ascariasis, hookworm, and trichuriasis. The NTD Control Program supported national NTD control and elimination programs' efforts to integrate and scale up delivery of preventive chemotherapy (PC) [2]. PC is the administration of safe, single-dose drugs, either alone or in combination, as a public health intervention against targeted NTDs. Administration is characterized by population-based diagnosis,population-based treatment,and implementation at regular intervals. PC can be delivered as universal chemotherapy (i.e., mass drug administration [MDA]), where the entire population of an area is targeted; targeted chemotherapy, where only high-risk groups (e.g., school age children) are targeted; or selective chemotherapy, where only screened individuals found or suspected to be infected are targeted [3]. Between October 2006 and March 2012, the program provided 589 million NTD treatments through the collaborative efforts of ministries of health, implementing partners, funders, and pharmaceutical donation programs. The implementation of integrated NTD programs at the full national scale remains an important objective in many endemic countries [4]–[8]. Several theoretical frameworks for integration have been proposed; most protocols stress the importance of long-term commitments and concerted efforts of partnerships to realize NTD control and elimination objectives [9]–[14]. However, there is currently a paucity of economic evidence on the costs of integrated PC delivery for NTDs, primarily due to the significant variation in program structures and operations [14]. Given the scarce resources and substantial costs associated with NTD control and elimination, there is therefore a need to accurately determine the cost of program implementation. It is also important to delineate funding commitments to ensure that additional assistance is used to complement available resources, rather than duplicate or replace previous efforts. To allow governments to more easily enumerate costs and funding commitments for NTD control and elimination, the NTD Control Program developed the Tool for Integrated Planning and Costing (TIPAC). The TIPAC, a versatile planning and costing instrument, is designed to be used by members of a NTD program at the national level. For countries with decentralized political structures, the TIPAC can also be implemented at a subnational administrative level. NTD program and financial managers are the primary users of the tool; the involvement of other personnel, including representatives from partner organizations and ministries of education, improves the accuracy and completeness of the TIPAC data. The TIPAC implementation process includes four main phases: Background data collection: country coordinators compile, review, and verify demographic, epidemiologic, and cost classification data. In countries where individual disease control programs are not integrated, this phase may generate fruitful discussions among stakeholders and stimulate collaboration on program planning, outreach, implementation, and monitoring. Data entry: a focal person appointed by the national program enters the planned activity costs. The national strategic plans for NTD control and elimination, also referred to as master plans, serve as the guiding documents for data entry. As the tool is populated, integration opportunities and areas of overlap and duplication are identified. After the costs are entered, stakeholder meetings are convened to identify drug and funding commitments. Finalization and approval: the entered data is reviewed by all stakeholders and approved for use by ministry of health representatives from the national NTD control and elimination program. Results application: the results can be used to inform and guide annual work plans, drug applications, donor coordination efforts, and advocacy and fundraising strategies. The TIPAC is able to convert the information in the tool for use during another funding year, thereby facilitating data entry in subsequent years. The aim of this feasibility study is to assess whether the TIPAC effectively informs and facilitates country program decision-making and the integration of program activities. This study presents excerpts from data collected in two African countries (Sierra Leone, fiscal year [FY] Oct. 2010–Sept. 2011, and Tanzania, FY Oct. 2010–Sept. 2011), one Asian country (Nepal, FY Jul. 2010–Jul. 2011), and one Latin American country (Haiti, FY Oct. 2011–Sept. 2012). The lessons learned from implementing the TIPAC in these four countries can guide the planning and costing of annual NTD control and elimination activities in other NTD-endemic countries.

Background Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. Methodology/Principal Findings To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications. Conclusions/Significance MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones., Author Summary Lymphatic filariasis (LF), commonly known as elephantiasis, is a profoundly disfiguring parasitic disease caused by thread-like nematode worms. This disease can often be disabling, thus reducing the potential productivity of the affected individuals. The WHO places the number of people at risk in 83 countries at 1.307 billion. This study was undertaken in seven countries—Burkina Faso, Ghana, Egypt, Tanzania, the Philippines, the Dominican Republic, and Haiti—using a common protocol to determine the costs of mass drug administration (MDA) programs to interrupt transmission of infection with LF, because there is lack of sufficient information about the costs of these programs. The results demonstrate that LF MDA is affordable and relatively inexpensive when compared to other public health programs. In the context of initiatives for integrating programs for the control and elimination of neglected tropical diseases, this study adds specifically to the relatively scarce body of information about the costs of MDA programs for LF. It also adds to the general knowledge about the application of methods that can be used to estimate the costs and cost-effectiveness of an integrated approach.

Background The Global Programme to Eliminate Lymphatic Filariasis recommends the transmission assessment survey (TAS) as the preferred methodology for determining whether mass drug administration can be stopped in an endemic area. Because of the limited experience available globally with the use of Brugia Rapid™ tests in conducting TAS in Brugia spp. areas, we explored the relationship between the antibody test results and Brugia spp. infection as detected by microfilaremia in different epidemiological settings. Methods The study analyzes the Brugia Rapid™ antibody responses and microfilaremia in all ages at three study sites in: i) a district which was classified as non-endemic, ii) a district which passed TAS, and iii) a district which failed TAS. Convenience sampling was done in each site, in one to three purposefully selected villages with a goal of 500 samples in each district. Results A total of 1543 samples were collected from residents in all three study sites. In the site which was classified as non-endemic and where MDA had not been conducted, 5 % of study participants were antibody positive, none was positive for microfilaremia, and age-specific antibody prevalence peaked at almost 8 % in the 25–34 year-old age range, with no antibody-positive results found in children under eight years of age. In the site that had passed TAS, 1 % of participants were antibody positive and none was positive for microfilaremia. In the site which failed TAS, 15 % of participants were antibody positive, 0.2 % were microfilaremic, and age-specific antibody prevalence was highest in 6–7 year olds (30 %), but above 8 % in all age levels above 8 years old. Conclusions These results from districts which followed the current WHO guidance for mapping, MDA, and implementing TAS, while providing antibody profiles of treated and untreated populations under programmatic settings, support the choice of antibody prevalence in the 6- and 7-year-old age group in TAS for making stopping MDA decisions. Since only one study participant was microfilaremic, no conclusions could be drawn about the relationship between antibodies and microfilaremia and further longitudinal studies are required to understand this relationship.