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.

Elimination of diurnally sub-periodic Wuchereria bancrofti in Andaman and Nicobar Islands, India, using mass DEC-fortified salt as a supplementary intervention to MDA.

Feasibility of implementing a DEC-fortified (DEC at 0.2% w/w and iodine) salt strategy to hasten elimination of diurnally sub-periodic Wuchereria bancrofti (DspWB) from the lone foci in Nancowry islands, Nicobar district, India, was assessed. This is a two-arm community-based study: one arm (12 villages, population 2936) received double fortified salt along with annual mass drug administration (MDA) of DEC plus albendazole (DEC-salt+MDA-arm), and another (14 villages; population 4840) received MDA under the National Filaria Elimination Programme. DEC salt was distributed on camp mode supplemented by door delivery. Monthly survey was carried out in fixed and random households to assess the coverage, usage of DEC salt and DEC content. The impact on prevalence of mf at community level and antigenaemia among children was assessed. A total of 21 metric tonnes of free-flow DEC salt manufactured by Tamil Nadu Salt Corporation, India, was distributed for 1 year. In the DEC-salt+MDA-arm, > 90% of the households received and used the DEC salt. DEC was within therapeutic range (0.2-0.32% w/w) in the samples collected from kitchens. Community mf prevalence reduced from 2.27 to 0.14% in the DEC-salt-arm (< 1% in all the villages) and 1.26 to 0.74% (> 1% in 4 out of 14 villages) in the MDA-arm. Ag prevalence reduced to zero from 1.0 (DEC-salt+MDA-arm) and 6.3% (MDA-arm) in 2-3 years old, 1.2 and 3.6% from 2.9 in the DEC-salt-arm and 4.5% in the MDA-arm among 6-7 years old. It was feasible to deliver DEC-fortified salt covering > 90% of the households with compliance reaching the elimination target in the islands.

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.

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.

Virtual screening of natural anti-filarial compounds against glutathione-S-transferase of Brugia malayi and Wuchereria bancrofti.

Glutathione-S-transferase also referred as GST is one of the major detoxification enzymes in parasitic helminths. The crucial role played by GST in various chronic infections has been well reported. The dependence of nematodes on detoxification enzymes to maintain their survival within the host established the crucial role of GST in filariasis and other related diseases. Hence, this well-established role of GST in filariasis along with its greater nonhomology with its human counterpart makes it an important therapeutic drug target. Here in this study, we have tried to explore the inhibitory potential of some of the well-reported natural ant-filarial compounds against the GST from Wuchereria bancrofti (W.bancrofti) and Brugia malayi (B.malayi). In silico virtual screening, approach was used to screen the selected natural compounds against GST from W.bancrofti and B.malayi. On the basis of our results, here we are reporting some of the natural compounds which were found to be very effective against GSTs. Along with we have also revealed the characteristic of the active site of BmGST and WbGST and the role of important active site residues involve in the binding of natural compounds within the active site of GSTs. This information will oped doors for using natural compounds as anti-filarial therapy and will also be helpful for future drug discovery.

Exploration of antifilarial activity of gold nanoparticle against human and bovine filarial parasites: A nanomedicinal mechanistic approach.

The present work seeks to explore the antifilarial activity of biopolymer functionalized gold nanoparticles (AuNPs) against human filarial parasite (Wuchereria bancrofti) through Nrf2 signaling for the first time. A natural polymer, chitosan is used along with Terminalia chebula extract to synthesize AuNPs following the principles of green chemistry. The probable mode of action of AuNPs as filaricidal agent has been investigated in detail using model filarial parasite, Setaria cervi (bovine parasite). Biopolymers inspired AuNPs exhibit superior antifilarial activity against both human and bovine filarial parasites, and are able to induce oxidative stress and apoptotic cell death in filarial parasites mediated through mitochondria. AuNPs also alter the Nrf2 signaling. In addition, the synthesized nanomaterials appear to be nontoxic to mammalian system. Thus the present mechanistic study, targeting human filarial parasites, has the potential to increase the therapeutic prospects of AuNPs to control lymphatic filariasis in the upcoming days.

Seroprevalence of lymphatic filariasis among migrant workers in Peninsular Malaysia.

Background: Malaysia aims to eliminate lymphatic filariasis (LF) by the year 2020, thus the potential threat of LF from migrant workers needs to be investigated. Methods: Brugian and bancroftian filariasis among 484 migrant workers from six countries were investigated using rapid tests based on detection of specific IgG4 antibodies against BmR1 (Brugia Rapid) and BmSXP recombinant antigens. Results: The seroprevalence of brugian filariasis was very low; however, bancroftian filariasis was notable among workers from India, Nepal and Myanmar. Conclusion: Malaysia is not endemic for Wuchereria bancrofti, but harbors the vectors for the parasite, thus the results showed that migrant workers should be monitored for this infection.

Mathematical modelling of lymphatic filariasis elimination programmes in India: required duration of mass drug administration and post-treatment level of infection indicators.

BACKGROUND: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. METHODS: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. RESULTS: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). CONCLUSION: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure.

Los tres premios Nobel de Medicina 2015 / The Three Nobel Prizes 2015

No disponible

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.

Avaliação da infecção filarial por Wuchereria bancrofti antes do início do tratamento massivo para eliminação da Filaríase Linfática no distrito de Murrupula, Província de Nampula-Moçambique / Evaluation of Wuchereria bancrofti filarial infection before massive treatment for elimination of Lymphatic Filariasis in Murrupula District, Nampula Province Mozambique

A Wuchereria bancrofti é responsável por mais de 90% dos casos da Filaríase Linfática no mundo todo. Em Moçambique, 103 distritos são endémicos para a doença com as prevalências mais altas na região norte do país. A eliminação da doença esta prevista para o ano 2020 e pode ser alcançada pelo tratamento massivo das populações das áreas endémicas durante 5-6 anos com ivermectina e albendazole. A avaliação do impacto do tratamento e a verificação da eliminação da doença carece de ferramentas de diagnóstico com sensibilidade suficiente para detectar os mais pequenos vestígios de infecção remanescente. Entre elas, o teste imunocromatográfico (ICT) para pesquisa do antígeno filarial circulante (AFC), a gota espessa (GE) de sangue para pesquisa de microfilárias (Mf) e a PCR para a detecção têm sido frequentemente utilizadas antes (baseline), durante e após a campanha de eliminação com vista a monitorar a situação de transmissão da doença. Assim, no presente inquérito de base (baseline) propusemo-nos a avaliar a presença da infecção filarial por Wuchereria bancrofti antes do início do tratamento massivo pelos métodos comummente utilizados (teste imunocromatográfico e gota espessa) e também faze-lo utilizando um método de detecção molecular (PCR) para o efeito de padronização da técnica. As amostras de sangue foram colhidas no período nocturno entre as 21h-2h da manhã por punção digital. O teste imunocromatográfico foi realizado durante o inquérito utilizando 100 µL de sangue. As lâminas foram coradas pelo Giemsa e duplamentes observadas ao microscópio óptico para contagem de microfilárias. O ADN foi extraído a partir de pequenas quantidades de sangue seco em papel de filtro utilizando o Kit comercial Dneasy® Blood & Tissue da QUIAGEN. A PCR foi realizada para amplificar um seguimento de 188 pb da região repetitiva do genoma de W. Bancrofti (SspI ) e, também para amplificar o gene mitocondrial Citocromo oxidase 1 (Cox1). Os produtos da PCR foram analisados por electroforese em gel de agarose (1,5 %) e tampão tris-borato-EDTA (TBE), e os fragmentos de ADN visualizados sob iluminação UV. Foram incluídos 678 indivíduos com idade média de 20,7 (SD= 16.71) anos. O AFC esteve presente em 26 % (176/678) dos indivíduos. A prevalência dos portadores de microfilária foi 12,4% (84/678) e a densidade microfilárial foi de 244,12 Mf Mf/mL. Cerca de 6,8% (46/678) dos inqueridos tinham algum tipo de sintoma relacionado a doença. A PCR para amplificação da região repetitiva SspI detectou 15,5 % (105/678) de casos de infecção, enquanto que a PCR para amplificação Cox1 detectou apenas 7,1% (48/678) que foram conduzidos ao sequenciamento. Foram analizadas 14 sequências e identificadas três mutaçoes em 12 delas. A pesquisa do AFC pelo ICT continua sendo o mais sensível indicador da infecção filarial por W. bancrofti enquanto que a PCR pode ser utilizada para determinar a microfilarêmia de forma eficiente e com mais sensibilidade que o método microscópico de gota espessa comumente utilizado nos programas de avaliação do impacto da administração massiva de drogas sobre a microfilarêmia.

The Wuchereria bancrofti is responsible for more than 90% of Lymphatic Filariasis worldwide cases. In Mozambique, 103 districts are endemic for the disease with the highest prevalence in the northern region of the country. The elimination of the disease is expected for 2020 and can be achieved by mass treatment of populations of the endemic areas for 5-6 years with ivermectin and albendazole. The treatment impact evaluation and verification of the desease elimination lacks diagnostic tools with sufficient sensitivity to detect the smallest traces of the remaining infection. Among them, the immunochromatographic test (ICT) for circulating filarial antigen (CFA) detention, the thick blood film(TBF) for microfilariae research (Mf) and PCR for parasite DNA detention have been frequently used before (in baseline), during and after elimination program to monitor the situation of the disease transmission. Therefore, in this baseline survey our purpose was to evaluate the presence of filarial infection by Wuchereria bancrofti before the mass treatment using the commonly diagnostic methods (immunochromatographic rapid test and thick blood film) and also using a molecular method (PCR) for technical standardization effect. Blood samples were collected during nocturnal period between 9 pm and 2 am by digital lancing. The rapid immunochromatographic card test (ICT) were performed during the survey using 100 µL of blood. The slides were stained with giemsa (10%) and double cheked for the microfilariae counting using optic microscope. The DNA was extracted from small amount blood dried on filter peper using Dneasy® Blood & Tissue commercial Quiagen kit. A PCR were performed to amplify 188 bp fragment of repetitive SspI region of the W. bancrofti genome, and also to amplify cytochrome oxidase 1 (COX1) mitochondrial gene. The PCR products were analyzed by electrophoresis of agarose gel (1,5%) and tris-borate-EDTA buffer (TBE), and the DNA fragments were visualized under UV illumination. We included 678 individuals whose average age was 20.7 (SD = 16.71) years. The CFA was present in 26% (176/678) of surveyed. The microfilaria prevalence was 12.4% (84/678) and the microfilárial density was 244.12 Mf Mf/mL. About 6.8% (46/678) of the surveyed had symptoms related to the disease. The PCR for the SspI aplification detected 15.5% (105/678) cases of filarial infection while the PCR for Cox1 amplification detected only 7.1% (48/678) cases which were conducted for sequencing. We analysed 14 sequences and identified three mutations in 12 of the sequences. The filarial circulating antigen research by ICT cards remains the most sensitive indicator of the W. bancrofti filarial infection while the PCR can be used to determine the microfilaraemia efficiently and with greater sensitivity than the thick blood film method wich is commonly used in the MDA impact evaluation programme.

Antifilarial effect of ursolic acid from Nyctanthes arbortristis: molecular and biochemical evidences.

A bio-assay guided fractionation and purification approach was used to examine in vitro antifilarial activities of the crude methanolic extract of Nyctanthes arbortristis as well as fractions and isolated compound. From ethyl-acetate fraction we isolated and identified a triterpenoid compound which has been characterized as ursolic acid (UA) by HPLC and NMR data. We are reporting for the first time isolation and identification of UA from the leaves of N. arbortristis. The crude extract and UA showed significant micro- as well as macrofilaricidal activities against the oocyte, microfilaria and adult of Setaria cervi (S. cervi) by dye exclusion test and MTT reduction assay. Significant microfilaricidal activity of UA was further proved against mf of W. bancrofti by viability assay. The findings thus provide a new lead for development of a suitable filaricide from natural products. The molecular mechanism of UA was investigated by performing TUNEL, Hoechst staining, Annexin V-Cy3, flow cytometric analysis and DNA fragmentation assay. Differential expressions of pro- and anti-apoptotic genes were observed at the transcription and translational levels in a dose-dependent manner. Depletion in the worm GSH level and elevation in the parasite GST, SOD and super oxide anion indicated the generation of ROS. In this investigation we are reporting for the first time that UA acts its antifilarial effect through induction of apoptosis and by downregulating and altering the level of some key antioxidants like GSH, GST and SOD of S. cervi.

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.

Diurnally subperiodic filariasis in India-prospects of elimination: precept to action?

The elimination of lymphatic filariasis in the Andaman and Nicobar Islands provides unique opportunities and challenges at the same time. Since these islands are remote, are sparsely populated, and have poor transport networks, mass drug administration programs are likely to be difficult to implement. Diurnally subperiodic Wuchereria bancrofti vectored by Downsiomyia nivea was considered for the scope of vector control options. Considering the bioecology of this mosquito, vector control including personal protection measures may not be feasible. However, since these islands are covered by separate administrative machinery which also plays an important role in regulating the food supply, the use of diethylcarbamazine (DEC)-fortified salt as a tool for the interruption of transmission is appealing. DEC-fortified salt has been successfully pilot tested in India and elsewhere, operationally used by China for eliminating lymphatic filariasis. Administration of DEC-fortified salt though simple, rapid, safe, and cost-effective, challenges are to be tackled for translating this precept into action by evolving operationally feasible strategy. Although the use of DEC-fortified salt is conceptually simple, it requires commitment of all sections of the society, an elaborate distribution mechanism that ensures the use of DEC-fortified salt only in the endemic communities, and a vigorous monitoring mechanism. Here, we examine the inbuilt administrative mechanisms to serve the tribal people, health infrastructure, and public distribution system and discuss the prospects of putting in place an operationally feasible strategy for its elimination.

The sharp end - experiences from the Tanzanian programme for the elimination of lymphatic filariasis: notes from the end of the road.

The Tanzania Lymphatic Filariasis Programme, which was launched in 2000, is, in terms of geographical coverage, among the largest disease-control programmes in Tanzania's history, currently reaching 9.4 million people in 34 districts. The issues associated with this programme's implementation are reviewed here, in the context of the various players/stakeholders involved. This article provides an insight of how the programme began and discusses key areas in the programme's design. Mainly, however, it gives some impressions of how the programme is perceived by, and how it affects, village healthworkers, patients and politicians - the people who contribute to the implementation of the programme at various levels.

Reduction in levels of plasma vascular endothelial growth factor-A and improvement in hydrocele patients by targeting endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline.

The treatment for hydrocele is expensive, invasive surgery-hydrocelectomy. A drug that could prevent or improve this condition could replace or supplement hydrocelectomy. In Ghana, 42 hydrocele patients participated in a double-blind, placebo-controlled trial of a six-week regimen of doxycycline, 200 mg/day. Four months after doxycycline treatment, patients received 150 mug/kg of ivermectin and 400 mg of albendazole, which is used for mass chemotherapy in this area. Patients were monitored for levels of Wolbachia sp., microfilaremia, antigenemia, plasma levels of vascular endothelial growth factor-A (VEGF-A) and stage/size of the hydrocele. Wolbachia sp. loads/microfilaria, microfilaremia, and antigenemia were significantly reduced in the doxycycline-treated patients compared with the placebo group. The mean plasma levels of VEGF-A were decreased significantly in the doxycycline-treated patients who had active infection. This finding preceded the reduction of the stage of hydrocele. A six-week regimen of doxycycline treatment against filariasis showed amelioration of pathologic conditions of hydrocele patients with active infection.

Antifilarial lead molecules isolated from Trachyspermum ammi.

Lymphatic filariasis is caused by infection with the parasitic filarial nematodes Wuchereria bancrofti, Brugia malayi and B. timori, transmitted by mosquitoes. The lack of an adulticidal drug poses a challenge to filariasis elimination, hence it is essential to develop an effective antifilarial drug which could either kill or permanently sterilize the adult worms. In the reported work the in vitro activity of a methanolic extract of fruits of Trachyspermum ammi (Apiaceae) against adult bovine filarial Setaria digitata worms has been investigated. A bioassay-guided fractionation was carried out by subjecting the crude extract to flash chromatography. HPLC analysis was done for the crude extract and active fraction. The crude extract and the active fraction showed significant activity against the adult S. digitata by both a worm motility and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction assays. The isolated active principle was chemically characterized by IR, (1)H-NMR and MS analysis and identified as a phenolic monoterpene. It was screened for in vivo antifilarial activity against the human filarial worm B. malayi in Mastomys coucha, showing macrofilaricidal activity and female worm sterility in vivo against B. malayi. The findings thus provide a new lead for development of a macrofilaricidal drug from natural products.