Coverage of preventive measures and surveillance for neglected tropical diseases in hard-to-reach communities in Ghana.

BACKGROUND: Neglected tropical diseases (NTDs) are a major public health burden which mainly affects poor populations living in tropical environments and hard-to-reach areas. The study sought to examine coverage of preventive efforts, and case surveillance for NTDs in hard-to-reach communities in Ghana. METHODS: The study investigated treatment efforts for lymphatic filariasis (LF), and onchocerciasis and schistosomiasis/soil transmitted helminths (SCH/STH) at household level, in difficult-to-access communities in Ghana. A total of 621 households were sampled from 6 communities in the Western, Oti and Greater Accra regions. RESULTS: Over 95% of the households surveyed were covered under mass drug administration (MDA) campaigns for lymphatic filariasis (LF) and onchocerciasis. More than 80% of households had received at least two visits by community drug distributors under the MDA campaigns in the last two years preceding the study. In addition, over 90% of households in the LF and onchocerciasis endemic communities had at least one member using anthelminthic medications under the MDA campaigns in the 12 months preceding the study. However, households where no member had taken anthelminthic medications in 12 months preceding the study were over 6 times likely to have someone in the household with LF. CONCLUSIONS: This study determined that SCH/STH, LF and onchocerciasis are of serious public health concern in some communities in Ghana. There is an urgent need for holistic practical disease control plan involving both financial and community support to ensure total control of NTDs in difficult-to-access communities is achieved.

Impact of Semi-Annual Albendazole on Lymphatic Filariasis and Soil-Transmitted Helminth Infection: Parasitological Assessment after 14 Rounds of Community Treatment.

Between October 2012 and October 2015, we conducted a community trial to assess the impact of semi-annual (twice yearly) community treatment with albendazole on lymphatic filariasis in Seke Pembe, a village in the Republic of the Congo. Semi-annual community treatment with albendazole has been continued in the community since October 2015. We conducted an additional parasitological assessment survey in October 2019, 6 months after the 14th round of semi-annual treatment. Between October 2012 and October 2015, Wuchereria bancrofti antigenemia and microfilaremia rates in the community had decreased from 17.3% to 4.7% and from 5.3% to 0.3%, respectively. In October 2019, the antigenemia rate had decreased further to 2.8% (19 of 687). No microfilariae were found in night blood smears from persons with circulating filarial antigenemia (0 of 16), suggesting that W. bancrofti transmission has been interrupted in Seke Pembe. Semi-annual albendazole treatments also reduced significantly infection rates with soil-transmitted helminths.

The impact of four years of semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: A community-based study in the Democratic Republic of the Congo.

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. CONCLUSION/SIGNIFICANCE: These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.

The roles of stakeholder experience and organizational learning in declining mass drug administration coverage for lymphatic filariasis in Port-au-Prince, Haiti: A case study.

The World Health Organization (WHO) defines an effective round of mass drug administration (MDA) for lymphatic filariasis (LF) as one that reaches at least 65% of the target population. In its first round of MDA in 2011-2012, the National Program to Eliminate LF in Haiti achieved a 79% epidemiological coverage in urban Port-au-Prince. In 2013, coverage dropped below the WHO threshold and has declined year-over-year to a low of 41% in 2017. We conducted a retrospective qualitative case study to identify key factors behind the decline in coverage in Port-au-Prince and ways to address them. Our findings suggest that the main contributors to the decline in MDA coverage appear to be the absence of effective documentation of practices, reporting, analysis, and program quality improvement-i.e., learning mechanisms-within the program's MDA design and implementation strategy. In addition to their contribution to the program's failure to meet its coverage targets, these deficits have resulted in a high cost for the MDA campaign in both lost momentum and depleted morale. Through a proposed operating logic model, we explore how the pathway from program inputs to outcomes is influenced by a wide array of mediating factors, which shape potential participants' experience of MDA and, in turn, influence their reasoning and decisions to take, or not take, the pills. Our model suggests that the decisions and behavior of individuals are a reflection of their overall experience of the program itself, mediated through a host of contextual factors, and not simply the expression of a fixed choice or preference. This holistic approach offers a novel and potentially valuable framing for the planning and evaluation of MDA strategies for LF and other diseases, and may be applicable in a variety of global health programs.

An Insight into the Discovery of Potent Antifilarial Leads Against Lymphatic Filariasis.

BACKGROUND AND OBJECTIVES: Lymphatic filariasis is a neglected tropical disease caused by infection with filarial worms that are transmitted through mosquito bites. Globally, 120 million people are infected, with nearly 40 million people disfigured and disabled by complications such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). Current treatments (ivermectin, diethylcarbamazine) have limited effects on adult parasites and produce side effects; therefore, there is an urgent to search for new antifilarial agents. Numerous studies on the antifilarial activity of pure molecules have been reported accross the recent literature. The present study describes the current standings of potent antifilarial compounds against lymphatic filariasis. METHODS: A literature search was conducted for naturally occurring and synthetic antifilarial compounds by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, and Springer, among others) from their inception until September 2019. RESULTS: Numerous compounds have been reported to exhibit antifilarial acitivity in adult and microfilariae forms of the parasites responsible for lymphatic filariasis. In silico studies of active antifilarial compounds (ligands) showed molecular interactions over the protein targets (trehalose-6-phosphate phosphatase, thymidylate synthase, among others) of lymphatic filariasis, and supported the in vitro results. CONCLUSION: With reference to in vitro antifilarial studies, there is evidence that natural and synthetic products can serve as basic scaffolds for the development of antifilarial agents. The optimization of the most potent antifilarial compounds can be further performed, followed by their in vivo studies.

In Vitro and In Vivo Antifilarial Activity of Standardized Extract of Calotropis procera Flowers against Brugia malayi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease that causes permanent disability (elephantiasis). Currently used antifilarial drugs are failing to control LF and there is resurgence in some areas. Looking for new antifilarial leads, we found that Calotropis procera plant parts have been used in traditional medicine for alleviating elephantiasis but the antifilarial activity is not known. OBJECTIVE: In the present study, the antifilarial activity of ethanolic extract (A001) and its hexane fraction (F001) of C. procera flowers was investigated using the human filarial parasite Brugia malayi. METHODS: A001 and F001 were tested for antifilarial activity using motility and 3-(4,5-dimethylthiazol-2- yl)-2,5 diphenyltetrazolium bromide (MTT) assays (in vitro) and in the rodent models B. malayi- Meriones unguiculatus and B. malayi-Mastomys coucha. In the rodent models, A001 and F001 were administered orally for 5 consecutive days, and the adult worm burden and course of microfilaraemia were determined. RESULTS: Both A001 and F001 showed microfilaricidal and macrofilaricidal activity in vitro. In animal models, A001 killed ~49-54% adult worms. In M. coucha model, F001 killed 12-60% adult worms in a dose (125-500 mg/kg) dependent manner; A001 and F001 suppressed microfilaraemia till days 91 and 35 post initiation of treatment, respectively. HPTLC revealed 0.61% lupeol, 0.50% ß-sitosterol and 1.50% triacontanol in F001. CONCLUSION: Flowers of C. procera have definite microfilaricidal and macrofilaricidal activities. Whether this activity is due to lupeol, ß-sitosterol and triacontanol found in the hexane fraction remains to be investigated. This is the first report on the antifilarial efficacy of flowers of the plant C. procera.

Profiling the best-performing community medicine distributors for mass drug administration: a comprehensive, data-driven analysis of treatment for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths in Uganda.

BACKGROUND: The most prevalent neglected tropical diseases are treated through blanket drug distribution that is reliant on lay community medicine distributors (CMDs). Yet, treatment rates achieved by CMDs vary widely and it is not known which CMDs treat the most people. METHODS: In Mayuge District, Uganda, we tracked 6779 individuals (aged 1+ years) in 1238 households across 31 villages. Routine, community-based mass drug administration (MDA) was implemented for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths. For each CMD, the percentage of eligible individuals treated (offered and ingested medicines) with at least one drug of praziquantel, albendazole, or ivermectin was examined. CMD attributes (more than 25) were measured, ranging from altruistic tendencies to socioeconomic characteristics to MDA-specific variables. The predictors of treatment rates achieved by CMDs were selected with least absolute shrinkage and selection operators and then analyzed in ordinary least squares regression with standard errors clustered by village. The influences of participant compliance and the ordering of drugs offered also were examined for the treatment rates achieved by CMDs. RESULTS: Overall, only 44.89% (3043/6779) of eligible individuals were treated with at least one drug. Treatment rates varied amongst CMDs from 0% to 84.25%. Treatment rate increases were associated (p value< 0.05) with CMDs who displayed altruistic biases towards their friends (13.88%), had friends who helped with MDA (8.43%), were male (11.96%), worked as fishermen/fishmongers (14.93%), and used protected drinking water sources (13.43%). Only 0.24% (16/6779) of all eligible individuals were noncompliant by refusing to ingest all offered drugs. Distributing praziquantel first was strongly, positively correlated (p value < 0.0001) with treatment rates for albendazole and ivermectin. CONCLUSIONS: These findings profile CMDs who treat the most people during routine MDA. Criteria currently used to select CMDs-community-wide meetings, educational attainment, age, years as a CMD, etc.-were uninformative. Participant noncompliance and the provision of praziquantel before albendazole and ivermectin did not negatively impact treatment rates achieved by CMDs. Engaging CMD friend groups with MDA, selecting CMDs who practise good preventative health behaviours, and including CMDs with high-risk occupations for endemic infections may improve MDA treatment rates. Evidence-based guidelines are needed to improve the monitoring, selection, and replacement of CMDs during MDA.

Comparison of the Impact of Annual and Semiannual Mass Drug Administration on Lymphatic Filariasis Prevalence in Flores Island, Indonesia.

We compared the impact of annual and semiannual mass drug administration (MDA) on the prevalence of Brugia timori and Wuchereria bancrofti in Flores Island. Two villages (Paga, B. timori only; Lewomada, co-endemic) received annual MDA with diethylcarbamazine/albendazole and a larger village (Pruda, co-endemic) received semiannual MDA. Infection parameters (microfilariae [Mf], antibodies to recombinant filarial antigen BmR1 [Brugia Rapid (BR)], and a test for W. bancrofti antigenemia [immunochromatographic test (ICT)]) were assessed before and after treatment. The crude Mf prevalence in Pruda decreased after five semiannual treatments from 14.2% to 1.2%, whereas the Mf prevalence in the other two villages decreased after three annual treatments from 3.9% to 0% and from 5% to 0.3%, respectively. ICT positivity prevalence in Pruda and Lewomada decreased from 22.9% and 6.5% to 7% and 0.8%, respectively, whereas BR antibody prevalence in Pruda, Lewomada, and Paga decreased from 28.9%, 31.7%, and 12.5% to 3.6%, 4.1%, and 1.8%, respectively. Logistic regression analysis indicated that that Mf, BR, and ICT prevalence decreased significantly over time and that for the Mf and ICT outcomes the semiannual treatment had higher odds of positivity. Model-adjusted prevalence estimates revealed that apparent differences in treatment effectiveness were driven by differences in baseline prevalence and that adjusted prevalence declined more rapidly in the semiannual treatment group. We conclude that in this setting, annual MDA was sufficient to reduce Mf prevalence to less than 1% in areas with low to moderate baseline prevalence. Semiannual MDA was useful for rapidly reducing Mf prevalence in an area with higher baseline endemicity.

Antifilarial activity of azadirachtin fuelled through reactive oxygen species induced apoptosis: a thorough molecular study on Setaria cervi.

Efficacious therapeutic strategies against lymphatic filariasis are always sought after. However, natural products are a promising resource for developing effective antifilarial agents. Azadirachtin, a significant tetranortriterpenoid phytocompound found in Azadirachta indica, was evaluated in vitro for antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion and MTT assay confirmed the antifilarial potential of azadirachtin against S. cervi with a median lethal dose (LC50) of 6.28 µg/ml for microfilariae (mf), and 9.55 µg/ml for adult parasites. Morphological aberrations were prominent in the histological sections of the azadirachtin-exposed parasites. Moreover, alterations in the reactive oxygen species (ROS) parameters in treated parasites were evident. Induction of apoptosis in treated parasites was confirmed by DNA laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and translation levels confirmed apoptosis execution at the molecular level. Changes in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence detailed the pharmacological effectiveness of azadirachtin as a possible therapeutic agent against filariasis.

Equity and efficiency in the scaled-up implementation of integrated neglected tropical disease control: the health economics protocol of the COUNTDOWN multicountry observational study in Ghana, Cameroon and Liberia.

INTRODUCTION: Worldwide, millions of individuals are affected by neglected tropical diseases (NTDs). They are frequently the poorest and most marginalised members of society. Their living conditions, among other things, make them susceptible to such diseases. Historically, several large-scale treatment programmes providing mass drug administrations (MDAs) were carried out per single disease but over the last decade there has been an increasing trend towards co-implementation of MDA activities given the resources used for such programmes are often the same. The COUNTDOWN multicountry studies focus on scaled-up implementation of integrated control strategies against four diseases: lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The objective of the COUNTDOWN economic study is to assess the multicountry implementation of control interventions in terms of equity, impact and efficiency. METHODS: The health economic study uses different analytical methods to assess the relationship between NTDs and poverty and the cost-effectiveness of different large-scale intervention options. Regression analysis will be used to study the determinants of NTD occurrence, the impact of NTDs on poverty, factors that hinder access to MDAs and the effect of NTDs on quality-of-life of those affected, including disability. Cost-effectiveness analyses of various integration methods will be performed using health economic modelling to estimate the cost and programme impact of different integration options. Here, cost-effectiveness ratios will be calculated, including multivariate sensitivity analyses, using Bayesian analysis. ETHICS AND DISSEMINATION: Ethics approval has been received both at the Liverpool School of Tropical Medicine and in all participating countries. Results of the various substudies will be presented for publication in peer-reviewed journals. STUDY DATES: 1 July 2016 to 30 June-October 2019.

Antifilarial activity of diterpenoids from Taxodium distichum.

BACKGROUND: Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi and B. timori, is a debilitating disease with an adverse social and economic impact. The infection remains unabated in spite of treatment with existing antifilarial drugs diethylcarbamazine (DEC) and ivermectin which are chiefly microfilaricides. There is therefore, need for macrofilaricides, embryostatic agents and better microfilaricides. In the present study we explored the antifilarial potential of crude extract and its molecular fractions of the plant Taxodium distichum using in vitro assay systems and rodent models of B. malayi infection. METHODS: Ethanolic extract (A001) of aerial parts of T. distichum was solvent fractionated and sub-fractionated. Four molecules, 3-Acetoxylabda-8(20), 13-diene-15-oic acid (K001), Beta-sitosterol (K002), labda-8(20),13-diene-15-oic acid (K003) and Metasequoic acid A (K004) were isolated from the fractions and their structure determined by spectroscopic analysis. The extract, subfractions and molecules were evaluated for antifilarial activity against B. malayi by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction and motility assays in vitro and in two animal models, Meriones unguiculatus and Mastomys coucha, harbouring B. malayi infection. RESULTS: A001 was effective in killing microfilariae (mf) and adult worms in vitro. The diterpenoid K003 produced 100 % reduction in motility of both mf and adult worms and > 80 % inhibition in MTT reduction potential of adult female worms. In B. malayi-M. unguiculatus model, A001 killed all the adult worms in > 80 % of infected animals. K003 was embryostatic (> 95 %) in this model. In the B. malayi-M. coucha model, K003 killed ~54 % of adult worms (macrofilaricidal activity) and rendered > 36 % female worms sterile; it also stopped any further rise in microfilaraemia after day 42 post-initiation of treatment. CONCLUSION: Ethanolic extract of aerial parts of the plant T. distichum possesses potent antifilarial activity and the active principle was localised to K003 which showed significant macrofilaricidal activity and late suppression of peripheral microfilaraemia and some embryostatic activity. These findings indicate that labdane diterpenoid molecule(s) may provide valuable leads for design and development of new macrofilaricidal agent(s). To the best of our knowledge, this is the first report on antifilarial efficacy of products from the plant T. distichum.

The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology.

This International Society of Lymphology (ISL) Consensus Document is the latest revision of the 1995 Document for the evaluation and management of peripheral lymphedema (1). It is based upon modifications: [A] suggested and published following the 1997 XVI International Congress of Lymphology (ICL) in Madrid, Spain (2), discussed at the 1999 XVII ICL in Chennai, India (3), and considered/ confirmed at the 2000 (ISL) Executive Committee meeting in Hinterzarten, Germany (4); [B] derived from integration of discussions and written comments obtained during and following the 2001 XVIII ICL in Genoa, Italy as modified at the 2003 ISL Executive Committee meeting in Cordoba, Argentina (5); [C] suggested from comments, criticisms, and rebuttals as published in the December 2004 issue of Lymphology (6); [D] discussed in both the 2005 XX ICL in Salvador, Brazil and the 2007 XXI ICL in Shanghai, China and modified at the 2008 Executive Committee meeting in Naples, Italy (7,8);[E] modified from discussions and written comments from the 2009 XXII ICL in Sydney, Australia, the 2011 XXIII ICL in Malmö, Sweden, the 2012 Executive Committee Meetings (9),and [F] from discussions at the 2013 XXIV ICL in Rome, Italy, and the 2015 XXV ICL in San Francisco, USA, as well as multiple written comments and feedback from Executive Committee and other ISL members during the 2016 drafting. The document attempts to amalgamate the broad spectrum of protocols and practices advocated worldwide for the diagnosis and treatment of peripheral lymphedema into a coordinated proclamation representing a "Consensus" of the international community based on various levels of evidence. The document is not meant to override individual clinical considerations for complex patients nor to stifle progress. It is also not meant to be a legal formulation from which variations define medical malpractice. The Society understands that in some clinics the method of treatment derives from national standards while in others access to medical equipment and supplies is limited; therefore the suggested treatments might be impractical. Adaptability and inclusiveness does come at the price that members can rightly be critical of what they see as vagueness or imprecision in definitions, qualifiers in the choice of words (e.g., the use of "may... perhaps... unclear", etc.) and mentions (albeit without endorsement) of treatment options supported by limited hard data. Most members are frustrated by the reality that NO treatment method has really undergone a satisfactory meta-analysis (let alone rigorous, randomized, stratified, long-term, controlled study). With this understanding, the absence of definitive answers and optimally conducted clinical trials, and with emerging technologies and new approaches and discoveries on the horizon, some degree of uncertainty, ambiguity, and flexibility along with dissatisfaction with current lymphedema evaluation and management is appropriate and to be expected. We continue to struggle to keep the document concise while balancing the need for depth and details. With these considerations in mind, we believe that this 2016 version presents a Consensus that embraces the entire ISL membership, rises above national standards, identifies and stimulates promising areas for future research, and represents the best judgment of the ISL membership on how to approach patients with peripheral lymphedema in the light of currently available evidence. Therefore, the document has been, and should continue to be, challenged and debated in the pages of Lymphology (e.g., as Letters to the Editor) and ideally will remain a continued focal point for robust discussion at local, national and international conferences in lymphology and related disciplines. We further anticipate as experience evolves and new ideas and technologies emerge that this "living document" will undergo further periodic revision and refinement as the practice and conceptual foundations of medicine and specifically lymphology change and advance.

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases.

Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.

Prevalence of lymphatic filariasis in a tea garden worker population of Dibrugarh (Assam), India after six rounds of mass drug administration.

BACKGROUND & OBJECTIVES: Lymphatic filariasis (LF) is endemic in the state of Assam and mass drug administration (MDA) programme for LF elimination is being implemented in the state since 2004. A study on prevalence of microfilaria (mf), disease endemicity and vector infection was carried out in a tea garden population of Dibrugarh, Assam (India) to assess the effect of ongoing MDA programme on elimination of LF. METHODS: Finger prick thick blood smears (20 mm3) were made from individuals aged ≥2 yr old during night blood survey in between 2000-0000 hrs during the period of November 2012 to February 2013. Blood smears were dehaemoglobinised, stained with Giemsa and examined under microscope for presence of mf. Indoor resting mosquitoes were collected during 0600-1000 hrs and female Culex quinquefasciatus were dissected and examined under microscope for larval forms of the parasite. RESULTS: A total of 634 blood smears were collected and screened for mf and 47 (7.41%) individuals were found microfilaraemic, with predominance of males (74.5%). Highest mf rate (20.0%) was seen in the males of 30-39 yr age group while in females, age group of 10-19 yr recorded maximum mf rate (5.48%). Entomological collection and dissection of Cx. quinquefasciatus revealed presence of larval stages of the parasite and infection and infectivity rates recorded were 13.20 and 3.70%, respectively. Chronic clinical manifestations in the form of elephantiasis and hydrocele were recorded in 33 (5.73%) subjects of the 575 examined. INTERPRETATION & CONCLUSION: Mass drug administration data showed six rounds of MDA with drug distribution coverage in between 63.42 and 95.93% in the study population. Out of 634 individuals examined 47 were found microfilaraemic giving an overall infection rate of 7.41%. Mosquito vector infection and infectivity rates were 13.20 and 3.70%, respectively. Presence of high mf rate, vector infectivity rate and clinical cases in the study population after six rounds of MDA warrants concerted efforts to be made for effective implementation and monitoring of MDA for success of LF elimination programme.

The impact of two semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in the Republic of Congo.

Implementation of mass drug administration (MDA) with ivermectin plus albendazole (ALB) for lymphatic filariasis (LF) has been delayed in central Africa because of the risk of serious adverse events in subjects with high Loa loa microfilaremia. We conducted a community trial to assess the impact of semiannual MDA with ALB (400 mg) alone on LF and soil-transmitted helminth (STH) infections in the Republic of Congo. Evaluation at 12 months showed that ALB MDA had not significantly reduced Wuchereria bancrofti antigenemia or microfilaria (mf) rates in the community (from 17.3% to 16.6% and from 5.3% to 4.2%, respectively). However, the geometric mean mf count in mf-positive subjects was reduced from 202.2 to 80.9 mf/mL (60% reduction, P = 0.01). The effect of ALB was impressive in 38 subjects who were mf-positive at baseline and retested at 12 months: 37% had total mf clearance, and individual mf densities were reduced by 73.0%. MDA also dramatically reduced the hookworm infection rate in the community from 6.5% to 0.6% (91% reduction), with less impressive effects on Ascaris and Trichuris. These preliminary results suggest that semiannual community MDA with ALB is a promising strategy for controlling LF and STH in areas with coendemic loiasis.

Virtual screening of traditional Chinese medicine (TCM) database: identification of fragment-like lead molecules for filariasis target asparaginyl-tRNA synthetase.

Lymphatic filariasis (LF) is a vector borne infectious disease caused by the nematode Wuchereria bancrofti, Brugia malayi, and Brugia timori. Over 120 million people are affected by LF in the world, of which two-thirds are in Asia. The infection restricts the normal flow of lymph from the infected area resulting in swelling of the extremities and causing permanent disability. As the available drugs for the treatment of LF are becoming ineffective due to the development of resistance, there is an urgent need to find new leads for drug development. In this study, asparaginyl-tRNA synthetase (AsnRS; PDB ID: 2XGT) essential for the protein bio-synthesis in the filarial nematode was used to carry out virtual screening (VS) of plant constituents from traditional Chinese medicine (TCM) database. Docking as well as E-pharmacophore based VS were carried out to identify the hits. The top scoring hits, Agri 1 (1,3,8-trihydroxy-4,5-dimethoxyxanthen-9-one-3-O-beta-D-glucopyranoside) and Agri 2 (5,7-dihydroxy-2-propylchromone 7-O-beta-D-glucopyranoside), constituents of Agrimonia pilosa, were selected for molecular dynamics (MD) simulation study for 10 ns. MD simulation showed that both the glycosides Agri 1 and Agri 2 were forming stable interactions with the target protein. Moreover, docking and MD simulation of the lead A (1,3,8-trihydroxy-4,5-dimethoxyxanthen-9-one; Mol. Wt.: 304.25; CLogP: 3.07) and lead B (5,7-dihydroxy-2-propylchromone; Mol. Wt.: 220.22; CLogP: 3.02), the aglycones of Agri 1 and Agri 2, respectively, were carried out with the target AsnRS. The in silico investigations of the aglycones suggest that the lead B could be a suitable fragment-like lead molecule for anti-filarial drug discovery.

Nanocurcumin: a novel antifilarial agent with DNA topoisomerase II inhibitory activity.

OBJECTIVE: The aim of this study is to evaluate the antifilarial, antiwolbachial and DNA topoisomerase II inhibitory activity of nanocurcumin (nano-CUR). METHODS: Nano-CUR formulations (F1-F6) were prepared using free radical polymerization and were characterized by particle size, morphology, encapsulation efficiency and in vitro release kinetics. Antifilarial potential was evaluated in vivo against Brugian filariasis in an experimental rodent model, Mastomys coucha, by selecting the formulation that maximized parasite elimination characteristics. Wolbachial status was determined by PCR and a relaxation assay was used to estimate DNA topoisomerase II inhibitory activity. RESULTS: Nano-CUR (F3) having a 60 nm diameter and 89.78% entrapment efficiency showed the most favorable characteristics for the elimination of filarial parasites. In vivo pharmacokinetic and organ distribution studies demonstrate significantly greater C(max) (86.6 ± 2.56 ng ml(-1)), AUC0-∞ (796 ± 89.8 ng d ml(-1)), MRT (19.5 ± 7.82 days) and bioavailability of CUR (70.02%) in the organs from which the adult parasites were recovered. The optimized nano-CUR (F3) (5 × 5 mg/kg, orally) significantly augmented the microfilariciadal and adulticidal action of CUR over free CUR (5 × 50 mg/kg, orally) or Diethylcarbamizine (50 mg/kg, orally) against the Brugia malayi Mastomys coucha rodent model. The PCR results showed complete elimination of wolbachia from the recovered female parasites. Interestingly, nano-CUR was also found to be a novel inhibitor of filarial worm DNA topoisomerase II, Setaria Cervi in vitro. CONCLUSION: This study recognizes the beforehand antimicrofilarial, antimacrofilarial, anti-wolbachial activity of nano-CUR (F3) over free forms and additionally its strong inhibitory action against the major target filarial parasite enzyme DNA topoisomerase II in vitro.

Towards elimination of lymphatic filariasis: social mobilization issues and challenges in mass drug administration with anti-filarial drugs in Tamil Nadu, South India.

India is a signatory to World Health Assembly resolution for elimination of lymphatic filariasis (LF) and National Health Policy has set the goal of LF elimination by 2015. Annual mass drug administration (MDA) is ongoing in endemic districts since 1996-97. Compliance rate is a crucial factor in achieving elimination and was assessed in three districts of Tamil Nadu for 10th and 11th treatment rounds (TRs). An in-depth study assessed the impact of social mobilization by drug distributors (DDs) in two areas from each of the three districts. Overall coverage and compliance for assessed TRs were 76.3 and 67.7% which is below the optimum level to achieve LF elimination. Modifiable determinants continue to be the reason for non-consumption even in the 11th TR and 20.8% were systematic non-compliers. In 76.4% of the cases, DDs failed to adhere to three mandatory visits as per the guidelines. Number of visits by DDs in relation to low and high MDA coverage areas showed a significant relationship (P ≤ 0.000). MDA is limited to drug distribution alone and efforts by DDs in preparing the community were inadequate. Probable means to meet the challenges in preparation of the community is discussed.

Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi.

Bioassay guided fractionation of ethanolic extract of the leaves of Bauhinia racemosa led to the isolation of galactolipid and catechin class of the compounds (1-7) from the most active n-butanol fraction (F4). Among the active galactolipids, 1 emerged as the lead molecule which was active on both forms of lymphatic filarial parasite, Brugia malayi. It was found to be better than the standard drug ivermectin and diethylcarbamazine (DEC) in terms of dose and efficacy.