"Whenever I tell her to wear slippers, she turns a deaf ear. She never listens": a qualitative descriptive research on the barriers to basic lymphedema management and quality of life in lymphatic filariasis patients in a rural block of eastern India.

BACKGROUND: Chronic lymphatic filariasis patients in Bihar, India, need management of lymphedema to live a disability-free life. For patients who have recurrent attacks of acute dermato-lymphangio-adenitis (ADLA), World Health Organization (WHO) has recommended simple home-based measures that include maintaining hygiene, skin care, and limb movement. However, patients in rural areas are unable to adopt them, resulting in a vicious cycle of ADLA attacks. There might be multiple realities from patients' and healthcare workers' perspectives that were unexplored. Qualitative research was deemed best suitable to identify the barriers to carrying out home-based lymphedema practices that adversely affected quality of life. METHODS: The qualitative descriptive study was conducted in two villages in the rural field practice area under a tertiary care hospital in Bihar. Researchers purposively selected ten participants, including patients affected by lymphedema, their caregivers, the grassroots healthcare workers, and the block health manager. In-depth interviews were conducted using a semi-structured interview guide. Data were entered into QDA Miner Lite, where researchers did attribute, in-vivo, process, descriptive, emotion, and holistic coding, followed by content analysis, where categories and themes emerged from the codes. RESULTS: Three themes emerged: the inherent nature of disease, patient-related factors, and healthcare system-related factors. The fifteen identified barriers were low awareness, low adherence, low health-seeking behavior, poor personal hygiene, and categories like signs and symptoms, seasonal factors, hampered activities of daily living, hopelessness from not getting cured, psychosocial difficulty, lack of capacity building and receipt of incentives by healthcare workers, unavailability of laboratory diagnosis and management of complications at the facility, inconsistent drug supply, and no financial assistance. CONCLUSIONS: Accessibility to WaSH, regular training of home-based care, increasing the capacity and motivation of grassroots workers, and the generation of in-depth awareness among the patients are required to achieve the elimination of filariasis, with MMDP as a key component of that strategy for endemic districts across the whole country.

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.

Immunodiagnostic potential of Wuchereria bancrofti L1 antigen-based filarial immunoglobulin G4 detection assay.

Background: After mass drug administration to eliminate human lymphatic filariasis, there is a need for surveillance to detect the measurable endpoint of the program. Methods: An immunodominant seroreactive clone, WbL1, was identified through immunoscreening of a Wuchereria bancrofti L3 complementary DNA expression library. Recombinant WbL1 (rWbL1) was analysed with sera from W. bancrofti patients. Diagnostic evaluation was carried out by developing an enzyme-linked immunosorbent assay (ELISA) to detect the filarial-specific antibodies in various categories of filarial sera samples against recombinant WbL1 (rWbL1) protein. Results: Performance parameters of the test in terms of immunoglobulin G (IgG) and IgG4 detection displayed significant sensitivity and specificity values up to 77% and 100%, respectively. Our results showed filarial antibodies against rWbL1 to be highly reactive with microfilaremic and clinical filarial sera samples compared with the endemic and non-endemic control sera samples. Reasonably satisfactory performance of the test was also confirmed from the multicentric evaluation of an anti-WbL1 IgG4 detection ELISA. This test was found to be minimally reactive with other nematode parasites and protozoan infections. Conclusions: The anti-WbL1 IgG4 detection test can be considered as a field test for initial screening and epidemiological monitoring of filarial infections in filariasis-endemic areas.

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.

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.

Filarial selenium glutathione peroxidase: a probable immunodiagnostic marker for lymphatic filariasis.

Lymphatic filariasis (LF) caused by Wuchereria bancrofti is widely prevalent in tropical and subtropical countries. Night blood film examination is most commonly used for diagnosis of filariasis but is cumbersome and labour intensive. In order to develop an indirect ELISA-based immunodiagnostic test, the importance of antifilarial IgG subclasses was evaluated in bancroftian filariasis patients. Blood samples from healthy individuals and different categories of LF patients were used to estimate the diagnostic potential of selenium glutathione peroxidase antigen purified from the bovine filarial parasite Setaria cervi. This antigen reacted with both IgG(1) and IgG(4); however, the IgG1 response was greater in microfilaraemic patients and the IgG(4) response was higher in chronic filarial patients. The diagnostic sensitivity of IgG(1) and IgG(4) was 97% and 96% whereas specificity was determined to be 95% and 98% respectively. Our observations suggest that SeGSHPx could be an alternative diagnostic marker for the detection of bancroftian filariasis in an endemic area.

[Genital elephantiasis: reconstructive treatment of penoscrotal lymphoedema with a myocutaneous M. gracilis flap. Experiences from a District Hospital in Ethiopia]. / Genitale Elephantiasis: Rekonstruktive Behandlung des penoskrotalen Lymphödems durch myokutane M. gracilis-Lappenplastik. Erfahrungen aus einem District Hospital in Athiopien.

BACKGROUND: Genital elephantiasis is an illness leading to serious functional and aesthetic as well as psychosocial impairment. Since the 19th century there have been articles describing methods for surgical ablative treatment of penoscrotal lymphoedema. However, most of these methods ignore the creation a new drainage for the lymph. We now describe a new technique using a myocutaneous M. gracilis muscle flap for the reconstruction of the soft tissue damage resulting from radical excision, thus ensuring drainage of the lymph into the deep muscle compartment of the thigh. PATIENTS AND METHOD: In the District Hospital "Mettu-Karl Hospital" in the Ethiopian rain forest region of Illubabor, during a period of 6 months the described surgical procedure was applied to 9 patients suffering from severe forms of this grotesquely disfiguring disease. Two patients presented with combined penoscrotal oedema, while the other 7 patients were suffering from isolated scrotal lymphoedema alone. All patients benefited from reconstruction with a myocutaneous M. gracilis muscle flap after radical excision of the affected tissue. All patients were evaluated after 3 and 12 months postoperatively in the presence of a translator. RESULTS: All nine patients showed a functionally and aesthetically satisfying result after 3 months without postoperative occurrence of infection. The evaluation 12 months postoperatively showed no recurrence of genitoscrotal lymphoedema. All patients reported on having regained normal ability for sexual intercourse and no occurrence of urinary tract infections since the operation. Concerning fertility, no statements could be made. A significant improvement in the quality of life was observed by the regained ability to walk and work and consequently the reintegration of the patients into their socio-economic environment. CONCLUSION: Radical excision of the affected tissue followed by transferring a functioning lymphatic drainage into the deep muscle compartment of the ipsilateral thigh using a proximally based myocutaneous gracilis muscle flap treats genital lymphoedema without recurrence. Satisfying aesthetic and functional results are achieved. The described surgical technique is still successfully being performed by two Ethiopian surgeons trained in this procedure.