Treatment Of Lymphatic Filariasis Research Articles

Factors associated with never treatment and acceptability of mass drug administration for the elimination of lymphatic filariasis in Guyana, 2021.

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA.

Drug- Phospholipid complex: A novel strategy for Lymphatic Filariasis treatment

One of the most terrifying and ugly forms of filariasis to humans is lymphatic filariasis, where adult worms 7-10 cm long are found in the lymphatic system. Mf continues to multiply in the bloodstream of the host and translocates eventually to the LS. Filariasis-causing parasites block the human blood vessels and lymph nodes.The impasse allows fluid to drain into the terminus of the body and accumulate in tissues, causing severe swelling christened “lymphoedema”. LF is caused due Filariodiaceae family roundworms, often these are of three types (Wuchereria bancrofti, Brugia malayi and Brugia timori). All of these are handed down through Anopheles mosquitoes, Aedes mosquitoes and Culex pipiens. In worldwide over 90% of infectious diseases are caused by W. bancrofti. Several synthetic drugs are currently used to treat this disease. However these drugs are not as effective as killing adult worms and at the same time, some side effects are also seen. Conversely, plant actives ingredients complex with phospholipids to form nano-sized vesicles. As parasites live in the small intestine, nanometer-sized phyto vesicles can protect plant actives from deterioration in the stomach and easily reach their target and kill parasites without side effects.

Pharmacokinetics of Moxidectin combined with Albendazole or Albendazole plus Diethylcarbamazine for Bancroftian Filariasis.

Moxidectin (MOX) is a milbemycin endectocide recently approved by the U.S. FDA for the treatment of onchocerciasis in persons at least 12 years of age. MOX has been shown to have a good safety profile in recent clinical trials. The efficacy of MOX for the treatment of lymphatic filariasis (LF) and its potential use in mass drug administration protocols for the elimination of LF is currently under evaluation. In the context of a clinical trial, we investigated the pharmacokinetics and drug interactions of a combination of MOX plus albendazole (ALB) with or without diethylcarbamazine (DEC) compared to ivermectin (IVM) plus ALB with or without DEC in the following four different treatment arms: (I) IVM (0.2mg/kg) plus DEC (6 mg/kg) and ALB (400mg); (II) IVM plus ALB; (III) MOX (8 mg) plus DEC and ALB; and (IV) MOX plus ALB. Drug concentrations were determined using validated liquid chromatography-mass spectrometric methods. Pharmacokinetic parameters were determined using standard non-compartmental analysis methods. Statistical analysis was performed using JMP software. Fifty-eight of 164 study participants (53 men and five women) were included with ages ranging from 18 to 63 yrs (mean = 37). MOX apparent oral clearance (Cl/F) ranged from 0.7 to 10.8 L/hr with Cmax values ranging from 20.8 to 314.5 ng/mL. The mean (range) area under the curve (AUC)0-∞ for MOX, 3405 ng*hr/mL (742-11376), and IVM 1906 ng*hr/mL (692-5900), varied over a ~15.3 and ~8.5-fold range, respectively. The geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were within the no-drug interaction range of 80-125% for all drugs. This indicates that the addition of MOX to ALB alone or ALB plus DEC for LF therapy did not alter the drug exposure of co-administered drugs compared to IVM combinations. Clinical Trial Registration: NCT04410406, https://clinicaltrials.gov/.

Self-care treatment for lymphoedema of lymphatic filariasis using integrative medicine.

Lymphatic filariasis (LF) is a neglected tropical disease presenting mainly as lymphoedema (elephantiasis). At present, LF is not effectively treated. Integrative medicine (IM) treatment for lymphoedema uses a combination of Indian traditional medicine, Ayurveda, alongside yoga exercises, compression therapy, antibiotics and antifungal treatments, providing a useful combination where resources are limited and different practices are in use. To assess the effectiveness of the IM in the existing clinical practice of lower-limb lymphoedema management and to determine whether the treatment outcomes align with the World Health Organization (WHO) global goal of LF management. Institutional data from electronic medical records of all 1698 patients with LF between 2010 and 2019 were retrospectively analysed using pre- and post-treatment comparisons and the National Institute for Health and Care Excellence guidelines for clinical audit. The primary treatment outcomes evaluated were limb volume, bacterial entry points (BEEPs), episodes of cellulitis, and health-related quality of life (HRQoL). Secondary outcomes included the influence of the patient's sex, duration of illness, education and employment status on volume reduction. Multiple regression analysis, t-test, χ2-test, analysis of variance, Mann-Whitney U-test and the Kruskal-Wallis test were used to assess the association between IM and patients' treatment outcomes. Limb volume reduced by 24.5% [95% confidence interval (CI) 22.47-26.61; n = 1660] following an intensive supervised care period (mean 14.84 days, n = 1660). Limb volume further reduced by 1.42% (95% CI 0.76-2.07; n = 1259) at the first follow-up visit (mean 81.45 days), and by 2.3% between the first and second follow-up visits (mean 231.32 days) (95% CI 1.26-3.34; n = 796). BEEPs were reduced upon follow-up; excoriations (78.4%) and intertrigo (26.7%) were reduced at discharge and further improvements was achieved at the follow-up visits. In total, 4% of patients exhibited new BEEPs at the first follow-up [eczema (3.9%), folliculitis (6.5%), excoriations (11.9%) and intertrigo (15.4%); 4 of 7 BEEPs were recorded]. HRQoL, measured using the disease-specific Lymphatic Filariasis Specific Quality of Life Questionnaire, showed an average score of 73.9 on admission, which increased by 17.8 at the first follow-up and 18.6 at the second follow-up. No patients developed new cellulitis episodes at the first follow-up, and only five patients (5.3%) developed new episodes of cellulitis at the second follow-up. IM for lower-limb lymphoedema successfully reduces limb volume and episodes of cellulitis, and also reduces BEEPs, leading to improved HRQoL. IM aligns with the LF treatment goals of the WHO and is a low-cost, predominantly self-care management protocol. IM has the potential to change care models and improve the lives of patients with lymphoedema.

IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis.

Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment. IgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to Wb-Bhp-1 and Wb123, but not Bm14, were significantly higher in participants with persistent microfilaremia 24 months after treatment. Antibodies to all three antigens declined significantly by 60 months after treatment with ivermectin, diethylcarbamazine and albendazole despite circulating filarial antigen in 76% of participants. By 60 months follow up, antibodies to Wb-Bhp-1, Wb123, and Bm14 were detected in 17%, 7% and 90% of participants, respectively. Antibodies to Wb-Bhp-1 also declined more rapidly after treatment than antibodies to Bm14 in samples from a clinical trial conducted in Sri Lanka. We also tested archived serum samples from people living in filariasis-endemic communities in Egypt with different infection profiles. Antibodies to Wb-Bhp-1 were detected in 73% of microfilaremic people, 53% of amicrofilaremic people with circulating filarial antigen, and 17.5% of endemic individuals without microfilaria or circulating filarial antigen. Tests performed with legacy samples from India showed that few people with filarial lymphedema had antibodies to these recombinant antigens. Antibodies to Wb-Bhp-1 and Wb123 are more closely correlated with persistent microfilaremia than circulating filarial antigenemia or antibodies to Bm14, and they clear more rapidly after anti-filarial treatment. Additional studies are needed to assess the value of Wb-Bhp-1 serology as a tool for determining the success of LF elimination efforts.

Dichrostachys cinerea (L.) Wight and Arn. (Fabaceae), a plant used in the traditional treatment of lymphatic filariasis in Côte d'Ivoire: Ethnopharmacological characteristics

Dichrostachys cinerea (L.) Wight & Arn. (Fabaceae) is a plant used in the traditional treatment of lymphatic filariasis. It was revealed following a recent ethnomedicinal survey. The present study aims to highlight the distinctive ethnopharmacological characteristics of Dichrostachys cinerea. The aim was to identify some groups of chemical compounds by thin layer chromatography, to assay some minerals and finally to characterise the specific anatomical and micrographic features of the plant. Terpenes and sterols, saponosides, flavonoids and tannins are the main phytocompounds revealed. Magnesium with 110.4 mg/100 g dry matter is the most abundant mineral. Anatomical sections revealed from the periphery to the interior of the organs, epidermis, collenchyma, cortical parenchyma, sclerenchyma, liber or phloem, the wood or xylem and the medullary parenchyma. In the plant powder, it was observed starch grains and calcium oxalate crystals. These results add to the data on Dichrostachys cinerea, a taxon much used in traditional Ivorian medicine for the treatment of lymphatic filariasis.

Is the neglected tropical disease mass drug administration campaign approach an effective strategy to deliver universal health coverage? A case study of the Liberia neglected tropical disease programme.

Access to affordable, quality healthcare is the key element of universal health coverage (UHC). This study examines the effectiveness of the neglected tropical disease (NTD) mass drug administration (MDA) campaign approach as a means to deliver UHC, using the example of the Liberia national programme. We first mapped the location of 3195 communities from the 2019 national MDA treatment data reporting record of Liberia. The association between coverage for onchocerciasis and lymphatic filariasis treatment achieved in these communities was then explored using a binomial geo-additive model. This model employed three key determinants for community 'remoteness': population density and the modelled travel time of communities to their supporting health facility and to their nearest major settlement. Maps produced highlight a small number of clusters of low treatment coverage in Liberia. Statistical analysis suggests there is a complex relationship between treatment coverage and geographic location. We accept the MDA campaign approach is a valid mechanism to reach geographically marginal communities and, as such, has the potential to deliver UHC. We recognise there are specific limitations requiring further study.

Discovery of potent inhibitors targeting Glutathione S-transferase of Wuchereria bancrofti: a step toward the development of effective anti-filariasis drugs.

Lymphatic filariasis (LF) is one of the major health problems for the human kind in developing countries including India. LF is caused by three major nematodes namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. The recent statistics of World Health Organization (WHO) showed that 51 million people were affected and 863 million people from 47 countries around worldwide remain threatened by LF. Among them, 90% of the filarial infection was caused by the nematode W. bancrofti. Approved drugs were available for the treatment of LF but many of them developed drug resistance and no longer effective in all stages of the infection. In the current research work, we explored the Glutathione S-transferase (GST) of W. bancrofti, the key enzyme responsible for detoxification that catalyzes the conjugation of reduced GSH (glutathione) to xenobiotic compounds. Initially, we analyzed the stability of the WbGST through 200 ns MD simulation and further structure-based virtual screening approach was applied by targeting the substrate binding site to identify the potential leads from small molecule collection. The in silico ADMET profiles for the top-ranked hits were predicted and the predicted non-toxic lead molecules showed the highest docking score in the range of -12.72 kcal/mol to -11.97 kcal/mol. The cross docking of the identified hits with human GST revealed the potential binding specificity of the hits toward WbGST. Through WbGST-lead complex simulation, the lead molecules were observed to be stable and also intactly bound within the binding site of WbGST. Based on the computational results, the five predicted non-toxic molecules were selected for the in vitro assay. The molecules showed significant percentage of inhibition against the filarial worm Setaria digitata which is the commonly used model organism to evaluate the filarial activity. In addition, the molecules also showed better IC50 than the standard drug ivermectin. The identified lead molecules will lay a significant insight for the development of new drugs with higher specificity and lesser toxicity to control and treat filarial infections.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Curative Innovation of Novel Triple-Drug Compared to Double-Drug Regimen in Lymphatic Filariasis: A Systematic Review

The World Health Organization has established a global program for the elimination of lymphatic filariasis by 2020; recent data has shown an impracticable result accomplishing it. Therefore, this study aims to identify the efficacy and safety between triple-drugs (DEC, ALB, IVM) and double-drugs (DEC & ALB/IVM & ALB) for lymphatic filariasis treatment. A systematic review was conducted with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guidelines. The literature search was done using five databases: PubMed, ProQuest, ScienceDirect, EBSCO, and CENTRAL until December 3, 2020 without any publication date range imposed. Data collection was done by three independent reviewers and entered into a predesigned data extraction form. Cochrane risk of bias tool 2.0 was utilized in the quality assessment of the studies. Search strategies identified 209 studies. Three relevant full-text articles met our inclusion criteria. Overall studies had low risk of bias. The main findings are as follows: (a) Administration of single dose of triple-drug regimen resulted in a total elimination of microfilaria 12 months after treatment whilst 91% participants given with double-drug remained microfilaremic (p=0.002); (b) In larger samples (n=182), triple drug cleared microfilaria in 96% of the participants and only 32% of the participants receiving double-drug regimen after 12 months observation; (c) Statistically, the triple-drug safety has a lower degree than the double-drug regimen (p=0.02). The triple-drug treatment has a better efficacy compared to the double-drug regimen in treating lymphatic filariasis. Furthermore, both regimens are proven safe with no serious adverse events elicited.

Theoretical modeling and design of some pyrazolopyrimidine derivatives as Wolbachia inhibitors, targeting lymphatic filariasis and onchocerciasis.

Lymphatic filariasis and onchocerciasis are two common filarial diseases caused by a group of parasitic nematodes called filarial worms, which play host to the bacteria organism Wolbachia. One good treatment approach seeks Wolbachia as drug target. Here, a QSAR study was conducted to investigate the anti-wolbachia activities (pEC50) of 52 pyrazolopyrimidine analogues, while using the built model to predict the pEC50 values of the newly designed analogues. Density Functional Theory was used for the structural optimization, while the model building was based on Genetic Function Algorithm approach. The built QSAR model was validated thus: R2 = 0.8104, R2 adj = 0.7629, Q2 cv = 0.6981, R2 test = 0.7501 and cRp2 = 0.7476. The predicted pEC50 of all newly designed compounds were higher than that of the template (43). The new compounds were; observed to pass the drug-likeness criteria, uniformly distributed to the brain, and found to be non-mutagenic. Also, the new compounds and the reference drug (doxycycline), were docked onto Ovarian Tumor (OTU) deubiquitinase receptor (PDB ID: 6W9O) using iGEMDOCK tool. This protein is known to help Wolbachia subvert host ubiquitin signaling. The resulting binding scores of the newly designed compounds except A5 were higher than that of doxycycline, while the protein-ligand interactions were majorly characterized by Hydrogen-bonding and hydrophobic interaction types. Therefore, the newly designed molecules could be developed as potential drug candidates for the treatment of lymphatic filariasis and onchocerciasis.

Current perspective of new anti-Wolbachial and direct-acting macrofilaricidal drugs as treatment strategies for human filariasis.

Filarial diseases like lymphatic filariasis and onchocerciasis belong to the Neglected Tropical Diseases and remain a public health problem in endemic countries. Lymphatic filariasis and onchocerciasis can lead to stigmatizing pathologies and present a socio-economic burden for affected people and their endemic countries. Current treatment recommendations by the WHO include mass drug administration with ivermectin for the treatment of onchocerciasis and a combination of ivermectin, albendazole and diethylcarbamazine (DEC) for the treatment of lymphatic filariasis in areas that are not co-endemic for onchocerciasis or loiasis. Limitations of these treatment strategies are due to potential severe adverse events in onchocerciasis and loiasis patients following DEC or ivermectin treatment, respectively, the lack of a macrofilaricidal efficacy of those drugs and the risk of drug resistance development. Thus, to achieve the elimination of transmission of onchocerciasis and the elimination of lymphatic filariasis as a public health problem by 2030, the WHO defined in its roadmap that new alternative treatment strategies with macrofilaricidal compounds are required. Within a collaboration of the non-profit organizations Drugs for Neglected Diseases initiative (DNDi), the Bill & Melinda Gates Foundation, and partners from academia and industry, several new promising macrofilaricidal drug candidates were identified, which will be discussed in this review.

Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire.

Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of 3 years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis. Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either 3 annual doses of IA (N = 52), 6 semiannual doses of ALB 400 mg (N = 45), or 6 semiannual doses of ALB 800 mg (N = 47). The primary outcome is amicrofilaremia at 36 months. IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, 95% confidence interval [CI]: 67-91; vs 48%, 95% CI: 32-66 and 57%, 95% CI: 41-73, respectively). Mean percentage reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, 95% CI: 88-100) than after ALB 400 mg (88%, 95% CI: 78-98) and ALB 800 mg (89%, 95% CI: 79-99) (P = .07 and P = .06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated. Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas where ivermectin cannot be used. NCT02974049.

The potentials of Calotropis procera against filarial elephantiasis: an in-silico approach.

Lymphatic filariasis is one of the major diseases that belong to the category of neglected tropical illness. Filarial nematodes are the cause of the disease and are transmitted to humans via blood-feeding arthropod vectors. Drugs such as Albendazole, Ivermectin and diethylcarbamazine are administered either individually or in combination to overcome the progress of the lymphatic filariasis. These drugs have some minor side effects like temporary hair loss, dizziness, nausea etc. The filarial parasites have multifunctional proteins including the Glutathione-s-transferase (GST) enzyme. This study aims at the identification of a natural molecule that has the potential to bind with the GST enzyme, which plays a major role in detoxification of endogenous electrophilic compounds. Thus the binding interrupts the detoxification process within the filarial parasite, Brugia malayi. A medicinal plant Calotropis procera, owing to its anthelmintic properties was searched for the presence of potential phytocompounds. The phytocompounds were docked against the homology modeled GST enzyme using the MOE software. The results were screened and analyzed based on the Lipinski rule of 5. N-octanoate was the phytocompound obtained based on molecular docking, subjected to molecular dynamics. These results require further in vitro and in vivo validation to consider n-octanoate as a potential drug candidate for lymphatic filariasis treatment.

#56: A novel test for diagnosis and surveillance of Wuchereria bancrofti infection

Abstract Background Elephantiasis or Lymphatic filariasis (LF) is a parasitic infection that causes significant morbidity and impacts hundreds of millions of people in 73 countries. Most LF is caused by the nematode Wuchereria bancrofti, but Brugia species cause LF in some areas of Southeast Asia. The global program to eliminate LF uses mass drug administration (MDA) of antifilarial drugs in endemic areas to kill the microfilaria (MF) stage of the parasite that is required for ongoing transmission by mosquitos. Better tools are needed for assessing the success of MDA, because of limitations of available diagnostic tests. MF testing is often not feasible, because it requires collection of blood at night in most endemic areas. Existing antibody and antigen tests remain positive long after effective treatment, and their results do not correlate well with current infectivity. The Brugia Rapid test detects antibodies to BmR1, a Brugia protein that is expressed by MF. These antibodies disappear 2–3 years after effective treatment, and that makes the Brugia Rapid test a useful marker for persistent infection in the few countries with brugian filariasis. We set out to develop a novel antibody test for W. bancrofti infection based on a BmR1 homologue in W. bancrofti. Methods We cloned, expressed and purified a Wuchereria bancrofti protein (provisional name WbN1) that is a homologue of the Brugia malayi protein BmR1. Sera from patients infected with Wuchereria bancrofti as well as sera from patients infected with other closely related filarial species were tested for IgG4 antibodies to WbN1 by indirect ELISA. Results The ELISA has a sensitivity of 90.7% for infection with W. bancrofti based on the 80 bancrofti patient samples tested thus far. Specificity was 91.5% with 59 sera samples from patients infected with Onchocerca volvulus or Loa loa, which are filarial parasites that are co-endemic with W. bancrofti in Africa. Specificity was 97.9% with North American control samples. ELISA with sera from a clinical trial in Sri Lanka demonstrated that antibodies to WbN1 decreased significantly faster after treatment than antibodies to the previously described filarial antigen Bm14. Similar declines in antibody to WbN1 occurred after patients in Papua New Guinea received a single dose of triple drug treatment for LF with Ivermectin Diethylcarbamazine and Albendazole, that is effective for clearing MF from the blood without clearing filarial antigenemia. Conclusions While additional studies are needed, this ELISA for IgG4 antibody to the recombinant protein WbN1 could be a promising new surveillance tool for assessing for ongoing transmission of LF following MDA.

Filaricidal activity of Daniellia oliveri and Psorospermum febrifugum extracts

BackgroundDrugs currently used for controlling onchocerciasis and lymphatic filariasis (LF) are mainly microfilaricidal, with minimal or no effect on the adult worms. For efficient management of these diseases, it is necessary to search for new drugs with macrofilaricidal activities that can be used singly or in combination with existing ones. Daniellia oliveri and Psorospermum febrifugum are two plants commonly used in the local management of these infections in Bambui, a township in the North West Region of Cameroon, but there is currently no documented scientific evidence to support their claimed anthelmintic efficacy and safety. The aim of this study was to provide evidence in support of the search for means to eliminate these diseases by screening extracts and chromatographic fractions isolated from these plants for efficacy against the parasitic roundworms Onchocerca ochengi and Brugia pahangi.MethodsThe viability of O. ochengi adult worms was assessed using the MTT/formazan assay. Fully confluent monkey kidney epithelial cells (LLC-MK2) served as the feeder layer for the O. ochengi microfilariae (mfs) assays. Viability of the mfs was assessed by microscopic examination for mean motility scoring (relative to the negative control) every 24 h post addition of an extract. The Worminator system was used to test the effects of the extracts on adult B. pahangi motility, and mean motility units were determined for each worm. Cytotoxicity of the active extracts on N27 cells was assessed using the MTS assay.ResultsExtracts from D. oliveri and P. febrifugum were effective against the adult roundworms O. ochengi and B. pahangi. Interestingly, extracts showing macrofilaricidal activities against O. ochengi also showed activity against O. ochengi mfs. The hexane stem bark extract of D. oliveri (DOBHEX) was more selective for adult O. ochengi than for mfs, with a half maximal and 100% inhibitory concentration (IC50 and IC100, respectively) against adult O. ochengi of 13.9 and 31.3 μg/ml, respectively. The in vitro cytotoxicity of all active extracts on N27 cells showed selective toxicity for parasites (selectivity index > 1). Bioassay-guided fractionation of the extracts yielded fractions with activity against adult B. pahangi, thus confirming the presence of bioactive principles in the plant extracts.ConclusionsOur study supports the use of D. oliveri and P. febrifugum in the traditional treatment of onchocerciasis and LF. The further purification of active extracts from these plants could yield lead compounds for filarial drug discovery and development.Graphical

An Overview of the Management of Mansonellosis.

Mansonellosis is caused by three filarial parasite species from the genus Mansonella that commonly produce chronic human microfilaraemias: M. ozzardi, M. perstans and M. streptocerca. The disease is widespread in Africa, the Caribbean and South and Central America, and although it is typically asymptomatic it has been associated with mild pathologies including leg-chills, joint-pains, headaches, fevers, and corneal lesions. No robust mansonellosis disease burden estimates have yet been made and the impact the disease has on blood bank stocks and the monitoring of other filarial diseases is not thought to be of sufficient public health importance to justify dedicated disease management interventions. Mansonellosis´s Ceratopogonidae and Simuliidae vectors are not targeted by other control programmes and because of their small size and out-door biting habits are unlikely to be affected by interventions targeting other disease vectors like mosquitoes. The ivermectin and mebendazole-based mass drug administration (iMDA and mMDA) treatment regimens deployed by the WHO´s Elimination of Neglected Tropical Diseases (ESPEN) programme and its forerunners have, however, likely impacted significantly on the mansonellosis disease burden, principally by reducing the transmission of M. streptocerca in Africa. The increasingly popular plan of using iMDA to control malaria could also affect M. ozzardi parasite prevalence and transmission in Latin America in the future. However, a potentially far greater mansonellosis disease burden impact is likely to come from short-course curative anti-Wolbachia therapeutics, which are presently being developed for onchocerciasis and lymphatic filariasis treatment. Even if the WHO´s ESPEN programme does not choose to deploy these drugs in MDA interventions, they have the potential to dramatically increase the financial and logistical feasibility of effective mansonellosis management. There is, thus, now a fresh and urgent need to better characterise the disease burden and eco-epidemiology of mansonellosis so that effective management programmes can be designed, advocated for and implemented.

Natural Products That Changed Society.

Until the end of the 19th century all drugs were natural products or minerals. During the 19th century chemists succeeded in isolating pure natural products such as quinine, morphine, codeine and other compounds with beneficial effects. Pure compounds enabled accurate dosing to achieve serum levels within the pharmacological window and reproducible clinical effects. During the 20th and the 21st century synthetic compounds became the major source of drugs. In spite of the impressive results achieved within the art of synthetic chemistry, natural products or modified natural products still constitute almost half of drugs used for treatment of cancer and diseases like malaria, onchocerciasis and lymphatic filariasis caused by parasites. A turning point in the fight against the devastating burden of malaria was obtained in the 17th century by the discovery that bark from trees belonging to the genus Cinchona could be used for treatment with varying success. However isolation and use of the active principle, quinine, in 1820, afforded a breakthrough in the treatment. In the 20th century the synthetic drug chloroquine severely reduced the burden of malaria. However, resistance made this drug obsolete. Subsequently artemisinin isolated from traditional Chinese medicine turned out to be an efficient antimalarial drug overcoming the problem of chloroquine resistance for a while. The use of synthetic analogues such as chloroquine or semisynthetic drugs such as artemether or artesunate further improved the possibilities for healing malaria. Onchocerciasis (river blindness) made life in large parts of Africa and South America miserable. The discovery of the healing effects of the macrocyclic lactone ivermectin enabled control and partly elimination of the disease by annual mass distribution of the drug. Also in the case of ivermectin improved semisynthetic derivatives have found their way into the clinic. Ivermectin also is an efficient drug for treatment of lymphatic filariasis. The serendipitous discovery of the ability of the spindle toxins to control the growth of fast proliferating cancer cells armed physicians with a new efficient tool for treatment of some cancer diseases. These possibilities have been elaborated through preparation of semisynthetic analogues. Today vincristine and vinblastine and semisynthetic analogues are powerful weapons against cancer diseases.

Coverage Validation Survey for Lymphatic Filariasis Treatment in Itang Special District of Gambella Regional State of Ethiopia: A Cross-Sectional Study.

BackgroundLymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia. In order to alleviate this problem Mass drug administration (MDA) has been given once a year for the public living in endemic sites. Despite this fact there might be a difference between reported coverage and the actual coverage on the ground due to various errors, so assessing the actual coverage through coverage validation survey appears imperative.ObjectiveThe aim of this survey was to assess the difference between the reported coverage and actual coverage of Ivermectin (IVM) and Albendazole (ALB) treatment given for Lymphatic Filariasis in Itang special district of Gambella regional state, Ethiopia.SettingThe study was conducted in Itang special district of Gambella region, the district was purposively selected for lymphatic filariasis treatment coverage survey. Eligible individuals aged 5 and above were interviewed. Data about the children were collected from parents or guardians and analyzed using STATA.ResultsThe survey showed that the coverage for LF treatment was 81.5%. From 825 individuals that reported that they were offered the treatment 823 (99.6%) swallowed the drug. The coverage in school age children (5–14) shows significant difference with treatment coverage in individuals aged 15 and above (p<0.001) in the last mass drug administration campaign. The main reason for not being offered preventive chemotherapy (PC) during the mass drug administration campaigns was missing class during the MDA (37.2%).ConclusionThe treatment coverage is higher than the recommended coverage of 65% of the target population. The coverage in school age children (5–14) showed significant difference with treatment coverage in individuals aged 15 and above. Improving the coverage level beyond this can significantly contribute to the LF elimination goal.