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BACKGROUND: Both endo- and ectoparasites pose a great challenge to the health of pigs worldwide, placing a significant burden on low-resource countries where veterinary care is minimal. As part of a larger clinical trial assessing the use of ivermectin (IVM) mass drug administration to humans and pigs for the control of malaria vectors in the Mopeia district in Mozambique, a longitudinal study to assess the impact of IVM administration on pig health was performed. METHODS: Beginning in March 2022, IVM was administered to pigs in the intervention area once a month for three consecutive months. Seventy pigs from the treatment group and 70 pigs from the control group were randomly selected for inclusion in the study. Fecal samples were collected monthly for three months and analyzed for the presence of strongyle eggs, strongyle eggs in the larval stage (strongyles – larval) and Ascaris suum using the modified McMaster test. Fecal samples were also collected two weeks after each dose of IVM was given to pigs in the treatment group for determination of a fecal egg reduction count. Juvenile pigs were measured twice a month for the first 3 months of the study, then once monthly for another three months. Visual exam for ectoparasites was performed on all pigs for the presence of ticks, lice or scabies at the same time points. RESULTS: Overall, 55% [95% CI: 48-62%] of pigs were positive for Ascaris suum, 95.2% [95% CI: 91-98%] were positive for strongyle eggs, and 72.5% [95% CI: 65.5-79%] were positive for strongyle – larval. A significant difference in the ivermectin treatment group was only seen one month after the second dose of ivermectin was administered: pigs in the treatment group had a 23.6% lower prevalence of strongyles (p = 0.003) and 18% lower prevalence of strongyles – larval (p = 0.03). Pigs in the treatment group also had lower EPG for Ascaris suum (diff = 102 EPG; p = 0.006), strongyles (diff = 642 EPG; p < 0.001), and strongyles - larval (diff = 217 EPG; p < 0.001). Analysis of covariance regression found no significant difference(P>0.05) in average daily weight gain (ADG) between the treatment and control groups. CONCLUSION: IVM delivered once monthly for three months has a small impact on pig health. To counteract the multiple health challenges pigs face in these settings, different dosing schedules along with education on husbandry issues related to nutrition and sanitation should be investigated in order to maximize impact on pig health. / Master of Science / A study was conducted in rural Mozambique in the district of Mopeia to determine the effectiveness of ivermectin against common parasites of swine when administered to pigs. The study began in March of 2022, at the beginning of rainy season, and ivermectin was given to pigs once a month for three months. Pigs were visited twice a month for the first three months, and then once a month for another three months. At various time points, fecal samples were collected, pigs were examined for evidence of ectoparasites (ticks, lice and scabies infestation), and young pigs were measured to determine their rate of growth. Fecal samples were analyzed for the presence of common internal parasites (endoparasites) affecting pigs in the area. The burden of endo and ectoparasites was estimated before any ivermectin was administered, and then compared in treated and untreated pigs over the course of the study. Similarly, the effect of ivermectin on growth rates in young animals was determined. The results of this study found that there was a high burden of common endoparasites in pigs in the Mopeia district, which was only minimally affected by the use of ivermectin delivered once a month. Among the treated pigs, a fecal egg count reduction test suggests that these parasites are potentially resistant to ivermectin, although other issues may be responsible for these results. The burden of ectoparasites was generally low (<10%), with ivermectin only significantly reducing the prevalence of ticks. Young animals that received ivermectin had a 15% increase in their growth rate, but this was not statistically significant. In conclusion, the use of ivermectin once a month for three months in pigs, as part of a malaria intervention, has some minimal positive health effects on treated pigs. Given the poor management practices, poor nutrition and lack of veterinary care in these pigs, it is likely that to have a greater impact on pig health, ivermectin will need to be delivered under a different dosing schedule and alongside owner education on pig management practices.

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Brugia malayi is one of the causative agents of the disabling and disfiguring disease known as Lymphatic Filariasis (LF). This infection is a well-established ailment in tropical and subtropical countries and recently the drug ivermectin has been introduced for the LF control programs. Ivermectin (IVM) is an excellent microfilaricide, but is not markedly macrofilaricidal. However, it causes a long-lasting reduction in the production of new larvae by female worms, suggesting that adult stages are affected. However, the mechanism by which IVM produces such effect in the adult worm is not well understood. One major reason is our incomplete understanding about the biological effect of IVM on adult stages. The present study was carried out to examine the in vitro effects of IVM on B. malayi adult worms using Brugia-gerbil animal model. And also to have some leads in understanding the drug-uptake and location of probable targets in the worm body by using fluorescent labeled IVM and confocal microscopy. / The antifilarial effects of IVM were examined using three parameters: mf release by female worms, and motility, and viability in both male and female worms. The results reported in this study demonstrate that although IVM did not kill the adult worm, but showed significant antifilarial effects on B. malayi adult stages when examined in an in vitro system. Confocal microscopy images of the worms incubated in bodipy FITC-IVM showed strong specific localization signal in the anterior cephalic region of both male and female worms. These observations suggest the early/initial interactions of the drug with its probable receptors that could be located specifically in the head region.

A current initiative to eliminate lymphatic filariasis (LF), headed by the World Health Organization, aims to interrupt transmission of the disease through yearly community-wide treatment with the broad spectrum anthelmintic albendazole (ABZ), in combination with ivermectin (IVM) or diethylcarbamazine (DEC). Over the years, the use of both ABZ and IVM in the treatment of veterinary parasites has led to widespread anthelmintic resistance against these drugs. In this study, we genotyped microfilaria of Wuchereria bancrofti, a causative agent of LF, in order to detect the presence of mutations which confer ABZ resistance in other parasites, and we identified such mutations in worms obtained from untreated patients in Ghana and Burkina Faso, West Africa. Microfilaria from patients who had been treated with ABZ + IVM, had a significantly higher frequency of the resistant genotype, and this frequency was even higher in worms from patients that had received two rounds of treatment. In addition, the untreated population of microfilaria had an excess of homozygotes in the population. This excess homozygosity was equivalent to a Wright's Inbreeding Statistic of FIT= 0.44, and we found that the population was significantly subdivided between patients. In order to better understand the mechanisms and factors involved in the potential spread of ABZ resistance, caused by such mutations, through a population of Culex-transmitted W. bancrofti, we developed a deterministic model that incorporates genotype structure into the epidemiological model EPIFIL. This model predicts that the combination of ABZ + DEC leads to stronger selection for the resistant genotype than ABZ + IVM, and that drug efficacy assumptions are an important factor affecting the spread of drug resistance. Treatment coverage, non-random mating, initial allele frequency and number of treatments also had substantial impact on the speed and magnitude of the spread of ABZ resistance. When we expanded this model to include potential IVM-resistance alleles we found that, under ABZ + IVM treatment, selection for resistance to either drug is enhanced by the presence of resistance against the second drug. Similarly, excess homozygosity caused by parasite non-random mating may increase selection for a dominant IVM resistance allele through enhancing the spread of a recessive ABZ resistance allele. Resistence developed more slowly when it was inherited as a polygenic trait. Results from this study suggest that resistance monitoring is crucial, as resistance may not be apparent until treatment is stopped, recrudescence occurs and treatment is reapplied.

No description available.

Extracellular adenosine-5'-triphosphate (ATP), released from damaged cells or coreleased as a cotransmitter from synaptic vesicles, acts on its plasma membrane receptors termed purinergic. Purinergic P2X receptors are ATP-gated cation channels. To date seven P2X isoforms designated P2X1-7 have been cloned that are organized as trimeric homomers or heteromers. All P2X subunits share a similar structure consisting of a large extracellular loop, two transmembrane domains and intracellular N- and C- termini. An additional structural feature is conserved aminoacids, these include ten conserved cysteine residues in the extracellular loop. All ectodomain cysteines form disulfide bonds which are organized in two areas: three disulfide bridges are localized in the N-termini half and two in the C-termini half at P2X receptor. ATP binding pocket is apparently localized between two neighbouring subunits. The aim of this Diploma Thesis was to examine the relevance of ectodomain cysteine residue and/or disulfide bonds for the expression, function and ATP binding properties of the P2X receptor. All ten, one by one, ectodomain cysteines were substituted by alanines and ATP-induced currents was recorded in HEK293 cells expressing wild-type P2X4 receptor and its mutants. Low responsible or nonfunctional mutants...

Estudo preliminar da redução da microfilaremia in vivo de Mansonella ozzardi (Manson, 1897) com uso de ivermectina, utilizando a técnica de filtração em membrana de policarbonato, Lábrea, Amazonas, Brasil. Estudou-se a eficácia do uso de dose única de ivermectina 0,15 mg/kg de peso no tratamento de 74 pacientes com infecção por Mansonella ozzardi. Inicialmente foi realizado a coleta de sangue para o diagnóstico parasitológico utilizando a filtração de sangue em membrana de policarbonato e para análises bioquímicas e hematológicas. Foi realizado a quantificação de microfilárias antes e depois do tratamento seguindo-os até 1 ano. Foi observado uma redução estatisticamente significativa em relação à densidade de microfilárias (&#967;2 de Friedman = 159,00; valor-p < 0, 0001) após 1 ano do uso da medicação, e que não houve alterações laboratoriais e efeitos adversos que comprometessem o uso da ivermectina. Concluiu-se que o fármaco nesta dose é eficaz e seguro, e mantém o \"clearance\" de microfilaremia pelo menos 1 ano após o uso. / Preliminary study of the reduction of microfilaremia in vivo of Mansonella ozzardi (Manson, 1897) with use of ivermectin, using the blood filtration polycarbonate membrane technique, in Labrea, Brazilian Amazon, Brazil. The study focused in the efficacy and tolerability of a single-dose use of ivermectin 0.15 mg / kg body weight in the treatment of 74 patients infected by the filarial worm M. ozzardi. Before and after the parasitological diagnosis by a blood filtration polycarbonate membrane and treatment, anamnesis, clinical examination and blood collection for quantification of microfilariae, biochemical and hematological analysis were done, comparing the outcomes of patients the in first day and after 72 hours and at least following up the patients for 1 year. The study concluded that there was a statistically significant reduction in microfilariaemia density (&#967;2 Friedman = 159, 00; p-value <0, 0001) after 1 year of use of the medication, and that there were no laboratory abnormalities and clinical symptoms that compromised the use of ivermectin. In conclusion, the use of ivermectin is an effective microfilaricide and maintains a suppressive effect for at least 1 year and the adverse reactions are not an obstacle for the treatment.

Dans ce travail, nous avons voulu apporter notre contribution dans le domaine de la recherche sur les poux humains, afin d’en savoir plus sur l’origine et la phylogéographie des clades, les pathogènes qui leurs sont associés et comprendre les mécanismes impliqués dans la résistance à l’ivermectine. Nous avons obtenu des résultats concrets dans chacune des thématiques abordées. En effet, nous avons (i) pour la première fois rapporté la présence de clade B au Moyen-Orient datant de plus de 2000 ans, supportant une origine asiatique pour ce clade, (ii) mis en évidence l'existence d'un nouveau clade mitochondrial (Clade F), (iii) mis en place une nouvelle technique de PCR en temps réel pour l’identification moléculaire rapide des clades de poux, (iv) mis en évidence chez des poux de tête la présence de l’ADN de plusieurs bactéries, dont plusieurs bactéries qui ne sont pas habituellement vectorisées par les poux telles que Coxiella burnetii, Rickettsia aeschlimannii et de potentielles nouvelles espèces de genre Anaplasma et Ehrlichia ont été détectées pour la première fois chez les poux. Enfin, nous rapportons des données nouvelles sur la résistance des poux à l’ivermectine : (v) en mettant en évidence la présence de trois mutations non-synonymes au niveau de GluCl des poux cliniquement résistants à l’ivermectine, (vi) et en démontrant, pour la première fois, chez une population de poux de laboratoire résistante à l’ivermectine qu’une répression significative de la complexine est à l’origine de la résistance. Cette découverte représente la première évidence liant la complexine à la résistance aux insecticides. / In this thesis, we are interested in studying human lice and we aimed to learn more about the origin and phylogeography of clades, lice-borne associated pathogens and to investigate potential mechanisms underlying resistance to ivermectin in lice. We obtained concrete results that have led to scientific publications. Indeed, (i) we reported for the first time the existence of the clade B in the Middle East, dating approximately to 2,000 years old, supporting an Asian origin for this clade, (ii) we highlighted the existence of a sixth mitochondrial clade (Clade F), (iii) we developed a new qPCR for a quick molecular identification of all the known clades of lice, (iv) we identified the presence of the DNA of several bacterial pathogens in head lice, among which several bacteria are not usually associated with lice, such as Coxiella burnetii, Rickettsia aeschlimannii, Borrelia theileri and potential new species from the Anaplasma and Ehrlichia. We finally, investigated mechanisms underlying resistance to ivermectin in lice: (v) we have identified, for the first time, the occurrence of three non-synonymous mutations in GluCl gene in clinically confirmed ivermectin resistant head lice, (vi) and we have identified the involvement of neuronal protein, a complexin, in laboratory ivermectin-selected resistant lice. This finding represents the first evidence linking complexin to insecticide resistance.