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Nematode parasite control in cattle is the goal of the parasitologist and the cattle producer. However, the language used to express the impact of that control has been a source of confusion between the two groups. Veterinary parasitologists speak in terms of reduction in worms or worm eggs, and cattle producers in terms of weight gain, milk production or calving rate. During the development of doramectin for cattle in temperate climates worldwide, the point came when we began to look for a different set of parameters to guide trial design and to communicate the results. In this paper, a series of published papers resulting from the yearling portion of this development programme are reviewed from the viewpoint of weight gain in relation to forage/feed availability. A pattern emerged that indicated that yearling cattle, when parasite control was effective (as indicated by egg counts) and forage was sufficient (as indicated by weather patterns), gained from 0.75 to 0.95 kg day(-1) in trials from the USA, Europe and Argentina. When parasite control or forage supply or both were insufficient, these rates of weight gain were significantly reduced. If more attention is spent on forage availability and weight-gain parameters when parasite-control programmes are designed, then researchers might communicate more meaningful information to producers on the value of parasite control.
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The cyclooctadepsipeptide PF1022A derived from the fungus, Mycelia sterilia, is characterized by a broad spectrum of activity against different parasitic gastrointestinal nematodes of livestock. In the present work the anthelmintic activity of PF1022A against Heligmosomoides bakeri, a widely used laboratory model was studied. Albendazole, ivermectin and levamisole served as reference. In vitro, PF1022A showed low activity on embryonation but significantly inhibited egg hatch (10 and 100 μg/ml), whereas albendazole (10 and 100 μg/ml) revealed statistically significant inhibitions of both embryonation and egg hatch. PF1022A (1-100 μg/ml) completely inhibited larval movement at most examination points. Comparable significant anthelmintic activity on the larval stages of H. bakeri was observed with levamisole (48-100%), while slightly lower activities were observed with ivermectin (20-92%) and albendazole (0-87%) at 1-100 μg/ml. PF1022A and levamisole significantly inhibited motility and egg release of adult worms, while albendazole and ivermectin failed to demonstrate activity. Significant worm burden reductions were achieved with PF1022A, levamisole and ivermectin in vivo. For example, at 0·125 mg/kg PF1022A a worm burden reduction of 91·8% was observed. The use of drug combinations did not further enhance the in vitro and in vivo activity of PF1022A. In conclusion, further investigations are warranted with PF1022A, as the drug is characterized by significant larvicidal and nematocidal activity in vitro and in vivo.
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It is pointed out that two of the three major groups of anthelmintic act by opening membrane ion-channels. It is appropriate, therefore, to use electrophysiological methods to study the properties of the sites of action of these drugs and the changes in the properties of these receptor sites associated with resistance. This paper describes the use of the patch-clamp technique to observe the currents that flow through the levamisole-activated channels as they open and close in levamisole-sensitive and levamisole-resistant isolates. It was found that, on average, the proportion of time the channels are open, is less in the resistant isolate. The patch-clamp technique also showed that the ion-channels are heterogeneous and that one of the subtypes is lost with the appearance of resistance. The use of the current clamp technique is illustrated to record a site of action of ivermectin in the pharyngeal muscle of Ascaris.
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Avermectins are 16-membered macrocyclic polyketides with potent antiparasitic activities, produced by Streptomyces avermitilis. Upstream of the avermectin biosynthetic gene cluster, there is the avtAB operon encoding the ABC transporter AvtAB, which is highly homologous to the mammalian multidrug efflux pump P-glycoprotein (Pgp). Inactivation of avtAB had no effect, but increasing the concentration of avtAB mRNA 30-500-fold, using a multi-copy plasmid in S. avermitilis, enhanced avermectin production about two-fold both in the wild-type and in a high-yield producer strain on agar plates. In liquid industrial fermentation medium, the overall productivity of avermectin B1a in the engineered high-yield producer was improved for about 50%, from 3.3 to 4.8 g/l. In liquid YMG medium, moreover, the ratio of intracellular to extracellular accumulation of avermectin B1a was dropped from 6:1 to 4.5:1 in response to multiple copies of avtAB. Additionally, the overexpression of avtAB did not cause any increased expression of the avermectin biosynthetic genes through RT-PCR analysis. We propose that the AvtAB transporter exports avermectin, and thus reduces the feedback inhibition on avermectin production inside the cell. This strategy may be useful for enhancing the production of other antibiotics.
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Baseline nodule and microfilaria ('skin snip') prevalence data were available from 10 hyperendemic sentinel communities in Cameroon (from 1996) and hyperendemic 20 sentinel communities in Uganda (from 1993). We returned to these villages in 2005, 10 months after the last annual ivermectin distribution, to repeat the cross-sectional surveys. Each sentinel community reported a mean interval treatment coverage of eligible persons of >88% (range 37-100%). Data were analyzed for more than 6200 person examinations. In Cameroon, 719 people >or=10 years were examined at the baseline survey in 1996 and 838 at the follow-up survey in 2005. In Uganda, 1590 people >or=10 years were examined at the baseline survey in 1993 and 2122 people at the follow-up survey in 2005. We also examined children under 10 in Cameroon (1996, n = 185; 2005, n = 448) and Uganda (1993, n = 177; 2005, n = 130). In Uganda, the vitality of worms was judged using standard histological criteria in 80 nodules excised in 2005.
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Two male and two female pet rabbits of about 1 year of age, naturally infested with Notoedres cuniculi were studied in the present investigation. Clinical examination revealed presence of crustaceous lesions on the head, ear pinnae, both the limbs and external genitalia. Microscopic examination of skin scrapings confirmed presence of Notoedres mange infestation. Biochemical parameters revealed altered values of total serum protein, albumin, globulin, and activities of aspartate amino transferase, alanine amino transferase and alkaline phosphatase respectively. The affected rabbits were treated with two injections of Ivermectin (400 μg/kg, subcutaneously, at interval of 15 days) along with supportive therapy. This treatment showed appreciable improvement in clinical signs and restoration in biochemical parameters.
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The aim of the present study was to carry out comparative therapeutic effect of moxidectin pour on, doramectin and ivermectin on psoroptes infestation in buffalo. A total of 318 buffalo in 77 small scale herds suspected to have mange mites were examined clinically and parasitologically. Fifty-three (16.66%) buffalo in 25 herds were recorded to be infested; 51 (16.35%) with psoroptic mites, and two (0.31%) with chorioptic mites. Buffalo with psoroptic mites were randomly allocated into three groups (17 buffalo each). First group was treated with moxidectin pour on at a dose rate of 0.5 mg kg(-1). The second group received doramectin (200 microg kg(-1) twice subcutaneously, 14 days apart). The third group received ivermectin (200 microg kg(-1) twice subcutaneously, 14 days apart). Adjunct to each drug, deltamethrin was applied to the surrounding environment twice at a two week interval. Treatment outcomes of 51 buffalo with psoroptic mites showed that moxidectin pour on and doramectin had a significant higher effect on mite count reduction (MANOVA, P < 0.01; Walks' Lambda, P < 0.01) and clinical sum scores (MANOVA, P < 0.05; Walks' Lambda, P < 0.05) compared with injectible ivermectin. On clinical level, the number of clinically recovered buffalo in moxidectin and doramectin treated groups was significantly (P < 0.05) higher than that of ivermectin treated group. The result of the present study indicated that psoroptic mites are the main cause of mange in buffalo in Lower Egypt. This is the first report that describes the effect of moxidectin in buffalo. Moxidectin is a good alternative and easily applied drug for treatment of psoroptes infestation in buffalo.
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This trial was conducted to test the efficacy of ivermectin/pyrantel chewables in preventing the development of Dirofilaria repens in dogs. The trial included 155 dogs from an endemic area in North-Western Italy. Prior to enrollment in the study, none of the dogs had microfilariae of D. immitis or D. repens in a concentration test, and all dogs were also seronegative for adult heartworm antigen. Animals remained with their owners and were dosed six times, at monthly intervals according to body weight. Efficacy against D. repens was evaluated approximately 6 and 12 months after the first dosing. None of the treated dogs was found to harbour microfilariae of D. repens or D. immitis on either occasion, whereas 6 of 24 untreated controls had circulating D. repens microfilariae at the final testing. The treatment was well accepted by all dogs.
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The presence of retinol-binding protein (RBP) activity in Onchocerca cervicalis adult worms and interaction with ivermectin has been studied using high pressure size exclusion chromatography (HPSEC). Four distinct peaks of [3H]-retinol incorporation were obtained corresponding to approximate molecular weights of 150, 67, 19.7 and 4.6 kDa, the 2 smaller M(r) peaks accounting for most of the binding activity. Competition for binding using non-labelled retinol at 200-fold molar excess indicated that specific binding of retinol occurred only to the 19.7 kDa fraction. Competition by ivermectin also inhibited binding of [3H]-retinol to the third peak. Following incubation with [3H]-ivermectin 4 peaks of similar molecular weights were also detected by HPSEC in soluble adult worm homogenate. However, in this case the 150 kDa fraction was most prominent. Both non-labelled ivermectin and non-labelled retinol at 200-fold molar excess reduced binding of [3H]-ivermectin to all 4 fractions. These data indicate that the putative Onchocerca RBP has an approximate molecular weight of 19.7 kDa, that retinol also binds to 3 additional fractions non-specifically, that the pattern of binding of ivermectin to adult worm material is quantitatively and qualitatively different from the binding exhibited by retinol, and that ivermectin interferes with the binding of retinol to the 19.7 kDa Onchocerca protein.
Donor-derived Strongyloides stercoralis infections in transplant recipients are a rare but recognized complication. In this case series, we report donor-derived allograft transmission of Strongyloides in three solid organ transplant recipients. Following detection of infection in heart and kidney-pancreas recipients at two different transplant centers, a third recipient from the same donor was identified and diagnosed. S. stercoralis larvae were detected in duodenal aspirates, bronchial washings, cerebrospinal fluid, urine and stool specimens. Treatment with ivermectin and albendazole was successful in two of the three patients identified. The Centers for Disease Control and Prevention was contacted and performed an epidemiologic investigation. Donor serology was strongly positive for S. stercoralis antibodies on retrospective testing while all pretransplant recipient serum was negative. There should be a high index of suspicion for parasitic infection in transplant recipients and donors from endemic regions of the world. This case series underscores the need for expanded transplant screening protocols for Strongyloides. Positive serologic or stool tests should prompt early treatment or prophylaxis in donors and recipients as well as timely notification of organ procurement organizations and transplant centers.
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Selamectin, a novel avermectin compound, was evaluated for its efficacy against naturally occurring infestations of Psoroptes cuniculi and Sarcoptes scabiei. A total of 42 New Zealand rabbits with psoroptic mange and 37 Angora rabbits with sarcoptic mange were used in the present study. On day 0, infested rabbits were treated topically with either selamectin at minimum dose of 6 mg kg(-1) (6-18 mg kg(-1) for New Zealand rabbits, n = 31 and 10-12 mg kg(-1) for Angora rabbits, n = 23) or vehicle only (control groups, n = 11 for New Zealand rabbits, n = 14 for Angora rabbits). The efficacy of selamectin was assessed both clinically and parasitologically by the presence or absence of viable mites. Rabbits were scraped for sarcoptic mites on days 7, 14, 28, 42 and 56 and had otoscopeic and/or microscopic examination for the detection of Psoroptes mites on days 7, 14, 42 and 56. Fisher's exact test was used to assess differences between the vehicle and selamectin treatment in the number of rabbits without mites (cure rates) on each assessment date. It was found that significantly fewer selamectin-treated rabbits had mites detected on skin scrapings (for S. scabiei) or otoscopeic and/or microscopic examination (for P. cuniculi) (P < 0.01) than the vehicle group. Results of the present study suggest that selamectin is effective against naturally infestations of P. cuniculi and S. scabiei in rabbits.
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Discovery of the CYP107Z subfamily of cytochrome P450 oxidases (CYPs) led to an alternative biocatalytic synthesis of 4''-oxo-avermectin, a key intermediate for the commercial production of the semisynthetic insecticide emamectin. However, under industrial process conditions, these wild-type CYPs showed lower yields due to side product formation. Molecular evolution employing GeneReassembly was used to improve the regiospecificity of these enzymes by a combination of random mutagenesis, protein structure-guided site-directed mutagenesis, and recombination of multiple natural and synthetic CYP107Z gene fragments. To assess the specificity of CYP mutants, a miniaturized, whole-cell biocatalytic reaction system that allowed high-throughput screening of large numbers of variants was developed. In an iterative process consisting of four successive rounds of GeneReassembly evolution, enzyme variants with significantly improved specificity for the production of 4''-oxo-avermectin were identified; these variants could be employed for a more economical industrial biocatalytic process to manufacture emamectin.
Following the demonstration of onchocercal skin disease's (OSD) public health and social importance in 1994, the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR) Task Force on Onchocerciasis Operational Research was asked to assess its economic impact. A multi-country study was subsequently undertaken in Ethiopia, Sudan, and Nigeria to measure the effect of OSD upon labor input and the effect of severe reactive skin disease in the household upon school attendance by children. Where the head-of-household had OSD, children were twice as likely to drop out of school compared to other children of the same age from the same community. The relationship was especially strong among girls, who were 2.6 times as likely to drop out of school if the head-of-household had OSD than if the head did not. It follows that onchocerciasis impedes educational development where OSD is highly prevalent. People with OSD spend US$20 more annually on health-related expenditures, 15% of their annual income, than do people without OSD. There are also significant time costs to having OSD. Another study was conducted in Uganda, Ghana, and Nigeria to assess the effect of ivermectin treatment upon OSD. Treatment led to a 40-50% decline in severe itching compared to placebo, sustained for up to 12 months after the first treatment. There was also a significant decline in the prevalence of reactive skin lesions following treatment compared to placebo.
The psyllid Bactericera cockerelli (Sulc) (Hemiptera: Psyllidae) is the vector of a bacterial pathogen causing zebra chip (ZC) disease in potato, Solanum tuberosum L. (Solanaceae). Recently, ZC has become important to potato growers and the potato chipping industry in the southwestern United States, Mexico, Central America, and New Zealand. In the current study, we evaluated the knockdown effect of 12 insecticides against adult B. cockerelli, and we examined the effects of treating potato leaves: top side only, bottom side only, or both sides. Within 48 h of exposure, abamectin showed the highest and most consistent rate of adult B. cockerelli mortality and a dosage response to three dosages within labeled field rates. Choice tests conducted in petri dishes, involving untreated potato leaves and leaves treated with abamectin, revealed that abamectin did not affect host preference of adult B. cockerelli. A residual test under field conditions revealed that, although highly effective immediately after application, abamectin-effect was nonsignificantly different from control treatments 24 and 48 h after field application. Higher adult B. cockerelli mortality was recorded from potato plants treated with ground application compared with aerial 48 h after application. Our results indicated that abamectin has a high knockdown effect on adult B. cockerelli and that it can be used effectively in insecticide rotation programs against adult B. cockerelli and ZC control in potatoes.
A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0-5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments.
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Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from avermectins isolated from fermentation products of Streptomyces avermitilis. Ivermectin showed a concentration-dependent inhibitory effect on motility of a free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific binding sites having a high affinity for ivermectin in the membrane fraction of C. elegans, and a strong positive correlation was detected between the affinity for these binding sites and the suppressive effect on motility of C. elegans in several ivermectin-related substances. These results suggested that the binding to these binding sites is important for the nematocidal activity of ivermectin. In oocytes of Xenopus laevis injected with the Poly (A)(+) RNA of C. elegans, expression of a chloride channel, which is irreversibly activated by ivermectin, was recognized. The pharmacological properties of this channel suggest that the ivermectin-sensitive channel is a glutamate-activated chloride channel. As to the glutamate-activated chloride channel, two subtypes (GluCl-alpha and GluCl-beta) were cloned, suggesting these subtypes constitute the glutamate-activated chloride channel. These findings suggest that ivermectin binds to glutamate-activated chloride channels existing in nerve or muscle cells of nematode with a specific and high affinity, causing hyperpolarization of nerve or muscle cells by increasing permeability of chloride ion through the cell membrane, and as a result, the parasites are paralyzed to death. In experimental infections in sheep and cattle, ivermectin exhibited potent dose-dependent anthelmintic effects on Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Oesphagostomum, and Dictyocaulus. Anthelmintic effects were reported also in dogs, horses, and humans infected with Strongyloides. In the clinical Phase III trial in Japan, 50 patients infected with Strongyloides stercoralis were administered approx. 200 microg/kg of ivermectin to be given orally twice at an interval of 2 weeks. As a result, the Strongyloides stercoralis-eradicating rate was 98.0% (49/50).
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The ivermectin accumulation in the everted gut sacs was higher in female compared with male intestine. The presence of PSC833 increased ivermectin accumulation profiles both in male and female rats. However, a greater response to transport modulation was observed in male compared with female animals. Similar results were obtained for Rho 123, where a higher absorption was measured in the intestine of females. PSC833 decreased Rho 123 intestinal secretion in animals of both sexes with a greater inhibition in male.
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Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C- domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions.
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A qualitative method based on thin-layer chromatography (TLC) is described that reliably detects ivermectin as a fluorescent derivative in extracts of cattle dung. The limit of detection (LOD) was < or = 40 ng/g of wet dung. These observations were statistically documented and shown visually using digital imagery. Residues were detected in fresh dung deposited by animals treated 10 days previously with a topical dose (500 microg/kg body weight) of ivermectin.
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Chronic parasitosis due to nematode worms (filariae) in tissue are very common in tropical ecosystems; their larvae (microfilariae) have been isolated in lymph vessels, skin, and blood. The case reported here is of a Nigerian patient suffering severe renal failure and admitted owing to the presence of a right submandibular gland abscess. In the FNAP, the presence of a Mansonella perstans microfilaria was identified. Post-surgery examination of pathology samples from the gland reported an acute inflammatory infiltrate including abundant eosinophils and microfilariae. There are some reports in the literature of haematic or lymphatic microfilariae, especially in epithelial or glandular tissues, and, as in this case, in inflammatory or malignant conditions. Both ivermectin and mebendazol are used for treatment; the scant pathogenicity of the genus Mansonella should, however, lead to an individualized decision.
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ONCHOSIM and EPIONCHO both predicted that in mesoendemic areas the pOTTIS can be reached with annual treatment, but that this strategy may be insufficient in very highly hyperendemic areas or would require prolonged continuation of treatment. For the lower endemicity levels explored, ONCHOSIM predicted that the time needed to reach the pOTTIS is longer than that needed to drive the parasite population to elimination, whereas for the higher endemicity levels the opposite was true. In EPIONCHO, the pOTTIS was reached consistently sooner than the breakpoint.
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Communities were mobilised for nodule palpation. A sample of thirty males aged at least 20 years, from each community that had lived in the area for at least ten years, were randomly selected and examined.
In New Brunswick, Canada, the sea louse, Lepeophtheirus salmonis, poses an on-going management challenge to the health and productivity of commercially cultured Atlantic salmon, Salmo salar. While the in-feed medication, emamectin benzoate (SLICE® ; Merck), has been highly effective for many years, evidence of increased tolerance has been observed in the field since late 2008. Although bioassays on motile stages are a common tool to monitor sea lice sensitivity to emamectin benzoate in field-collected sea lice, they require the collection of large numbers of sea lice due to inherent natural variability in the gender and stage response to chemotherapeutants. In addition, sensitive instruments such as EC(50) analysis may be unnecessarily complex to characterize susceptibility subsequent to a significant observed decline in efficacy. This study proposes an adaptation of the traditional, dose-response format bioassay to a fixed-dose method. Analysis of 657 bioassays on preadult and adult stages of sea lice over the period 2008-2011 indicated a population of sea lice in New Brunswick with varying degrees of susceptibility to emamectin benzoate. A seasonal and spatial effect was observed in the robustness of genders and stages of sea lice, which suggest that mixing different genders and stages of lice within a single bioassay may result in pertinent information being overlooked. Poor survival of adult female lice in bioassays, particularly during May/June, indicates it may be prudent to consider excluding this stage from bioassays conducted at certain times of the year. This work demonstrates that fixed-dose bioassays can be a valuable technique in detecting reduced sensitivity in sea lice populations with varying degrees of susceptibility to emamectin benzoate treatments.
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Individuals positive for at least one nodule were expressed in terms of Nodule Prevalence Rates (NPR) which were used to map the distribution of onchocerciasis.
We retrospectively studied all returning travellers with HrCLM who consulted in our institution. Patients were then treated with a single, 200 μg/kg dose of ivermectin, orally.
The aim of this study is to verify the level of transmission of lymphatic filariasis three years after stopping mass drug treatment in the 7 endemic districts in Togo. The survey was conducted in 2012 in Togo's 7 endemic districts grouped into four evaluation units (EU) using the WHO-recommended transmission assessment survey (TAS) protocol. Children aged 6-7 years were screened for Wuchereria bancofti antigen using the immunochromatographic card (ICT) method. A cluster sampling method was used to select eligible children in schools as the net primary-school enrolment ratio is greater than or equal to 75% in each of the four EUs. The number of children and schools to be selected in each EU, the randomization list for the selection of these children and the critical cut-off number of positive cases not to exceed were automatically generated using the Survey Sample Builder (SSB) tool, (NTD Support Center, Atlanta, Ga, USA). For confirmation, positive cases were subsequently tested for microfilaremia using nocturnal thick blood smear and for filarial antigen using Og4C3 antigen ELISA (TropBio ELISA Kit®, Townsville, Queensland, Australia). An EU is considered to have passed the test successfully (it is assumed that transmission can no longer be sustained), when the number of positive cases is below the critical cut-off number set by the SSB, which is roughly equivalent to 2% prevalence. Of the 1 706 children surveyed in Kpendjal-Tone's EU, 1 549 in Binah-Doufelgou's EU, 1 550 in Kozah's EU and the 1 575 in Amou-Haho's EU, 8 (0.46%), 1 (0.08%), 0 (0.00%) and 4 (0.25%) ICT positive cases respectively were detected. The number of positive ICT tests was well below 18, the critical cut number for each of the 4 EUs. All 13 ICT positive cases tested negative for nocturnal microfilaremia and Og4C3 ELISA. We conclude that all four EU passed the TAS with success, and the transmission of Wuchereria bancrofti is no longer likely to be sustained in the 7 endemic districts in Togo 3 years after stopping the MDA. A new TAS will be carried out in 2015, after which, if the results are still good, the country will submit a dossier to WHO for verification of the elimination of lymphatic filariasis.