"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 integrative therapeutic approach to elephantiasis nostras verrucosa: A case report.

Elephantiasis nostras is a chronic disorder that is difficult to treat. It is characterized by marked lymphedema, associated with hyperkeratosis, ulceration, deep skin folds and a cobblestone appearance of the skin. Causes include parasitic and bacterial infections, neoplasia and obesity, but numerous cases have uncertain aetiology. Treatment includes surgery and medication, which are associated with variable results. In the present study, a 72-year old female with renal insufficiency presented with leg enlargement of 3-4 years duration, which rendered her housebound. Examination showed massive lower limb enlargement, with typical cobblestone appearance. She was on furoseminde 80 mg/day. A diagnosis of elephantiasis nostras was made. Then, she was treated with increased furosemide from 80 to 120 mg daily and homeopathic Apocynum cannabinum, CH30 potency, t.d.s. Unavailability of corresponding fit excluded the use of compressive stockings. The patient remitted over 18 months, with limb diameters dropping from 68/46 cm (right mid-calf/ankle) and 67/43 cm (left mid-calf/ankle) to 64/43 cm (right mid-calf/ankle) and 64.5/45 cm (left mid-calf/ankle) at 6 months, 63/42 cm (right mid-calf/ankle) and 65/41 cm (left mid-calf/ankle) at 12 months, and 46/35 cm (right mid-calf/ankle) and 48/36 cm (left mid-calf/ankle) at 18 months, with improvement of skin appearance. Elephantiasis nostras is not spontaneously remitting. In this resource-limited setting, furosemide combined with homeopathic Apocynum cannabinum has proved valuable and may be used for similar cases.

Hybrid Treatment Combining Lymphaticovenous Anastomoses and the Oriental Herbal Medicine Bofutsushosan for Obesity-Associated Lower Leg Elephantiasis Nostras Verrucosa: A Case Report.

Elephantiasis nostras verrucosa (ENV) is a rare dermatological disease associated with chronic lymphedema caused by obesity, soft tissue infection, or chronic venous insufficiency. Although surgical debridement may be sufficient to treat the skin manifestations of ENV, treatment of ENV should focus on reducing lymph stasis to improve the skin changes and prevent recurrence. In this case report, we present the case of a 79-year-old woman who developed obesity-associated ENV in the lower leg. She was successfully treated by a combination of lymphaticovenous anastomoses and the oriental herbal medicine Bofutsushosan. To our knowledge, this is the first reported obesity-associated ENV case in which skin pathology was not only healed, but both edema relief and weight loss were successful. A treatment combining both surgery and the herbal medicine could be a potential therapeutic candidate for obesity-associated ENV.

High Throughput and Computational Repurposing for Neglected Diseases.

PURPOSE: Neglected tropical diseases (NTDs) represent are a heterogeneous group of communicable diseases that are found within the poorest populations of the world. There are 23 NTDs that have been prioritized by the World Health Organization, which are endemic in 149 countries and affect more than 1.4 billion people, costing these developing economies billions of dollars annually. The NTDs result from four different causative pathogens: protozoa, bacteria, helminth and virus. The majority of the diseases lack effective treatments. Therefore, new therapeutics for NTDs are desperately needed. METHODS: We describe various high throughput screening and computational approaches that have been performed in recent years. We have collated the molecules identified in these studies and calculated molecular properties. RESULTS: Numerous global repurposing efforts have yielded some promising compounds for various neglected tropical diseases. These compounds when analyzed as one would expect appear drug-like. Several large datasets are also now in the public domain and this enables machine learning models to be constructed that then facilitate the discovery of new molecules for these pathogens. CONCLUSIONS: In the space of a few years many groups have either performed experimental or computational repurposing high throughput screens against neglected diseases. These have identified compounds which in many cases are already approved drugs. Such approaches perhaps offer a more efficient way to develop treatments which are generally not a focus for global pharmaceutical companies because of the economics or the lack of a viable market. Other diseases could perhaps benefit from these repurposing approaches.

Assessing the feasibility of integration of self-care for filarial lymphoedema into existing community leprosy self-help groups in Nepal.

BACKGROUND: Lymphatic filariasis (LF) and leprosy are disabling infectious diseases endemic in Nepal. LF infection can lead to lymphoedema and hydrocoele, while secondary effects of leprosy infection include impairments to hands, eyes and feet. The disabling effects of both conditions can be managed through self-care and the supportive effects of self-help groups (SHGs). A network of SHGs exists for people affected by leprosy in four districts in Nepal's Central Development Region, however no such service exists for people affected by LF. The aim of this study was to determine the feasibility of integrating LF affected people into existing leprosy SHGs in this area. METHODS: A survey was conducted using a semi-structured questionnaire to elicit information on: (i) participant characteristics, clinical manifestation and disease burden; (ii) participants' knowledge of management of their condition and access to services; and (iii) participants' knowledge and perceptions of the alternate condition (LF affected participants' knowledge of leprosy and vice versa) and attitudes towards integration. RESULTS: A total of 52 LF affected and 53 leprosy affected participants were interviewed from 14 SHGs. On average, leprosy affected participants were shown to have 1.8 times greater knowledge of self-care techniques, and practiced 2.5 times more frequently than LF affected participants. Only a quarter of LF affected participants had accessed a health service for their condition, compared with 94.3% of leprosy affected people accessing a service (including SHGs), at least once a week. High levels of stigma were perceived by both groups towards the alternate condition, however, the majority of LF (79%) and leprosy (94.3%) affected participants stated that they would consider attending an integrated SHG. CONCLUSIONS: LF affected participants need to increase their knowledge of self-care and access to health services. Despite stigma being a potential barrier, attitudes towards integration were positive, suggesting that the SHGs may be a good platform for LF affected people to start self-care in this area. TRIAL REGISTRATION: This is not a registered trial.

Oleanolic acid from antifilarial triterpene saponins of Dipterocarpus zeylanicus induces oxidative stress and apoptosis in filarial parasite Setaria digitata in vitro.

Absence of a drug that kills adult filarial parasites remains the major challenge in eliminating human lymphatic filariasis (LF); the second leading cause of long-term and permanent disability. Thus, the discovery of novel antifilarial natural products with potent adulticidal activity is an urgent need. In the present study, methanol extracts of leaves, bark and winged seeds of Dipterocarpus zeylanicus (Dipterocarpaceae) were investigated for macro and microfilaricidal activity. Two antifilarial triterpene saponins were isolated from winged seed extracts by bioactivity guided chromatographic separation and identified using Nuclear Magnetic Resonance and mass spectroscopic analysis as oleanolic acid 3-O-ß-D- glucopyranoside (1) (IC50 = 20.54 µM for adult worms, 19.71 µM for microfilariae ) and oleanolic acid 3-O-α-L-arabinopyranoside (2) (IC50 = 29.02 µM for adult worms, 25.99 µM for microfilariae). Acid hydrolysis of both compounds yielded oleanolic acid (3) which was non or least toxic to human peripheral blood mono nuclear cells (Selectivity index = >10) while retaining similar macrofilaricidal (IC50 = 38.4 µM) and microfilaricidal (IC50 = 35.6 µM) activities. In adult female worms treated with 50 and 100 µM doses of oleanolic acid, condensation of nuclear DNA, apoptotic body formation and tissue damage was observed by using Hoechst 33342 staining, TUNEL assay and Hematoxylin and Eosin staining respectively. A dose dependent increase in caspase 3/CED3 activity and decrease in total protein content were also observed in these parasites. A dose dependant DNA fragmentation was observed in adult parasites and microfilariae. Decreased levels of reduced glutathione (GSH) and elevated levels of glutathione S transferase (GST), superoxide dismutase (SOD) and reactive oxygen species (ROS) were also observed in parasites treated with oleanolic acid indicating an oxidative stress mediated apoptotic event. Compound 3/oleanolic acid was thus identified as a potent and safe antifilarial compound in vitro.

Rhizome extracts of Curcuma zedoaria Rosc induce caspase dependant apoptosis via generation of reactive oxygen species in filarial parasite Setaria digitata in vitro.

Human lymphatic filariasis (LF) is mainly caused by filarial parasite Wuchereria bancrofti and is the second leading cause of long term and permanent disability in tropical countries. To date, incapability to eliminate long lived adult parasites by current drugs remains the major challenge in the elimination of LF. Hence, in the current study, the efficacy of rhizome extracts of Curcuma zedoaria (a plant traditionally used in Sri Lanka in the management of LF) was evaluated as an effective filaricide in vitro. Sequential solvent extracts of C. zedoaria rhizomes were screened for in vitro antifilarial activity at 0.01-1 mg/mL concentrations by motility inhibition assay and 3-(4, 5 dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) reduction assay using cattle parasite Setaria digitata as a model organism. Exposure of parasites to hexane and chloroform extracts of C. zedoaria caused a dose dependant reduction in motility and viability of microfilariae (IC50 = 72.42 µg/mL for hexane extract, 191.14 µg/mL for chloroform extract) and adult parasites (IC50 = 77.07 µg/mL for hexane extract, 259.87 µg/mL for chloroform extract). Both extracts were less toxic to human peripheral blood mononuclear cells when compared to filariae. A dose dependant increase in caspase 3/CED 3 and a decrease in total protein content, cyclooxygenase (COX) and protein tyrosine phosphatase (PTP) activities were observed in adult parasites treated with hexane or chloroform extract. A significant degree of chromatin condensation and apoptotic body formation were also observed in these worms by Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining respectively. Dose dependant chromosomal DNA laddering was observed in treated adult worms but not in microfilariae in response to both extracts. Oxidative stress parameters such as reduction in reduced glutathione (GSH) levels and increase in glutathione s transferase (GST), superoxide dismutase (SOD) and catalase activities, increased reactive oxygen levels (ROS) and lipid peroxidation were also observed indicating that an apoptotic event is induced by reactive oxygen species.

An Integrative Therapeutic Concept for Surgical Treatment of Severe Cases of Lymphedema of the Lower Extremity.

BACKGROUND: Lymphedema results from insufficient lymphatic drainage and typically affects the extremities. Recent studies revealed obesity as another cause of extremity lymphedema. Conservative treatment of patients with elephantiastic lymphedema of the lower extremity is limited and often inadequate. Resecting surgery plays an important role in these cases. Here, we investigated the effects of an integrated therapy concept on outcome and complication rates. METHODS: We retrospectively analyzed the clinical outcome of 26 patients with elephantiastic lymphedema of the lower limb who underwent a complex decongestive physical therapy (CDP) perioperatively and reduction surgery in our clinic between 1998 and 2011. We subsequently compared these patients (group A) with a control group of 30 patients (group B) who received medial thigh lift due to post-bariatric or aesthetic issues between 2011 and 2013. The incidence of complications, reoperations, blood transfusion, and duration of hospital stay was analyzed. All patients in group A received CDP perioperatively in a specialized lymphological clinic. RESULTS: Both groups are comparable in terms of age and sex. Patients significantly differ in terms of BMI (p < 0.001). Thirty-six reductive procedures were performed in group A and 30 in group B. We did not see any significant difference in the incidence of complications (p = 1.000) and the rate of postoperative blood transfusions (p = 0.116). CONCLUSIONS: We were able to show that an integrative concept including surgery is a good additional option for the treatment of severe cases of lymphedema in appropriate candidates. Furthermore, an adequate perioperative conservative setting helps to minimize possible complications.

Maggot Therapy for Elephantiasis Nostras Verrucosa Reveals New Applications and New Complications: A Case Report.

Elephantiasis nostras verrucosa (ENV) is a rare dermatologic condition caused by chronic nonfilarial lymphedema. The treatment for ENV is challenging and based solely on case reports. We report novel therapy for ENV with maggot debridement therapy (MDT), an effective wound therapy that has gained popularity with the rise of antimicrobial resistance. MDT, in combination with tangential surgical debridement, was effective in the treatment of ENV. In nature, sheep infested with more than 16 000 blow fly larvae exhibit ammonia toxicity. Although hyperammonemia as a side effect of maggot therapy has been theorized, its existence has not been described in human studies until this case. This patient exhibited hyperammonemia during maggot therapy; with alterations in serum ammonia reflecting changes in larval population. Maggot therapy should be considered for the treatment of ENV. Hyperammonemia with maggot therapy exists, and clinicians who employ this treatment should be aware of this potential adverse effect.

Large reduction in volume with the intensive treatment of lymphedema: reduction of fluids?

The aim of this study is to report on the intensive treatment of lymphedema of the legs demonstrating a large reduction in volume in a short period of time. The case of a 29-year-old female patient, who developed the most serious form of lymphedema, associated with verrucosities of the leg and genitalia is reported. Elephantiasis evolved after surgery and radiotherapy. The patient was treated at the Clinica Godoy in Sao Jose do Rio Preto, Brazil using an intensive course of treatment. Baseline and then daily evaluations of the leg perimeter and body weight were performed during treatment. Intensive treatment for 8 hours daily was performed on an outpatient basis using manual and mechanical (RAGodoy device, São Jose do Rio Preto, São Paulo-Brazil) lymph drainage and the continuous use of a compression garment made of a cotton-polyester textile and adjusted every 3 hours. A reduction of 31 kg was seen in 10 days (over 2 weeks); in the first few days, the patient lost 6 kg per day. Due to the excess of skin, the length of intensive treatment sessions was reduced to avoid the compression garment causing a tourniquet effect, the size of the compression stocking was only adjusted once per day and daily walks were included in the treatment program. After 1 month, the size of the leg was reduced by another 4 kg. Intensive lymphedema treatment is an option that rapidly reduces edema, and constant use of low-stretch compression maintains the result achieved and continues to reduce the swelling.

Isoterápico de Culex sobre o ciclo biológico domosquito Culex sp / Isotherapic of Culex on the biological cycle of the mosquito Culex sp

Introduction: Culex is an insect of the family Culicidae. It occurs in tropical and subtropical regions. It is known as the domestic mosquito. Their larvae develop in stagnant and dirty water, with plenty of organic matter. Some species of the insect such as Culex quinquefasciatus transmit the worms (helminths) called Wuchereria bancrofti filariasis or Elephantiasis.(AU)

Introdução: O Culex é um inseto da família Culicidae. Ele ocorre em regiões tropicais e subtropicais. Éconhecido como mosquito doméstico. Suas larvas se desenvolvem em água parada e suja, com muita matériaorgânica. Algumas espécies do inseto, como Culex quinquefasciatus transmite os vermes (helmintos) chamadoWuchereria bancrofti filiarose ou Elefantíase.(AU)