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2.
PLoS Negl Trop Dis ; 13(10): e0007778, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658264

RESUMO

BACKGROUND: A DNA extraction and preservation protocol that yields sufficient and qualitative DNA is pivotal for the success of any nucleic acid amplification test (NAAT), but it still poses a challenge for soil-transmitted helminths (STHs), including Ascaris lumbricoides, Trichuris trichiura and the two hookworms (Necator americanus and Ancylostoma duodenale). In the present study, we assessed the impact of different DNA extraction and preservativation protocols on STH-specific DNA amplification from stool. METHODOLOGY AND PRINCIPAL FINDINGS: In a first experiment, DNA was extracted from 37 stool samples with variable egg counts for T. trichiura and N. americanus applying two commercial kits, both with and without a prior bead beating step. The DNA concentration of T. trichiura and N. americanus was estimated by means of qPCR. The results showed clear differences in DNA concentration across both DNA extraction kits, which varied across both STHs. They also indicated that adding a bead beating step substantially improved DNA recovery, particularly when the FECs were high. In a second experiment, 20 stool samples with variable egg counts for A. lumbricoides, T. trichiura and N. americanus were preserved in either 96% ethanol, 5% potassium dichromate or RNAlater and were stored at 4°C for 65, 245 and 425 days. DNA was extracted using the DNeasy Blood & Tissue kit with a bead beating step. Stool samples preserved in ethanol proved to yield higher DNA concentrations as FEC increased, although stool samples appeared to be stable over time in all preservatives. CONCLUSIONS: The choice of DNA extraction kit significantly affects the outcome of NAATs. Given the clear benefit of bead beating and our validation of ethanol for (long-term) preservation, we recommend that these aspects of the protocol should be adopted by any stool sampling and DNA extraction protocol for downstream NAAT-based detection and quantification of STHs.


Assuntos
Fezes/parasitologia , Helmintíase/diagnóstico , Helmintos/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Preservação Biológica/métodos , Solo/parasitologia , Adolescente , Ancylostoma/genética , Ancylostoma/isolamento & purificação , Ancylostomatoidea/genética , Ancylostomatoidea/isolamento & purificação , Ancylostomatoidea/parasitologia , Animais , Ascaríase/diagnóstico , Ascaríase/parasitologia , Ascaris lumbricoides/genética , Ascaris lumbricoides/isolamento & purificação , Criança , Pré-Escolar , DNA/isolamento & purificação , Helmintíase/parasitologia , Helmintos/genética , Humanos , Necator americanus/isolamento & purificação , Necatoríase/diagnóstico , Necatoríase/patologia , Contagem de Ovos de Parasitas , Sensibilidade e Especificidade , Tricuríase/diagnóstico , Tricuríase/parasitologia , Trichuris/genética , Trichuris/isolamento & purificação
3.
PLoS Negl Trop Dis ; 13(8): e0007446, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369558

RESUMO

BACKGROUND: Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs). METHODOLOGY: We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs. PRINCIPAL FINDINGS: All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.


Assuntos
Testes Diagnósticos de Rotina/métodos , Helmintíase/parasitologia , Helmintíase/transmissão , Helmintos/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Solo/parasitologia , Adolescente , Animais , Brasil , Criança , Testes Diagnósticos de Rotina/instrumentação , Etiópia/epidemiologia , Fezes/parasitologia , Feminino , Helmintíase/diagnóstico , Helmintíase/epidemiologia , Helmintos/genética , Humanos , Laos/epidemiologia , Masculino , Microscopia , Técnicas de Diagnóstico Molecular/instrumentação , Contagem de Ovos de Parasitas/métodos , Prevalência , Sensibilidade e Especificidade , Tanzânia/epidemiologia , Organização Mundial da Saúde
4.
PLoS Negl Trop Dis ; 13(8): e0007471, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369562

RESUMO

BACKGROUND: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. METHODS: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. PRINCIPAL FINDINGS AND CONCLUSIONS: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the ß-tubulin gene that have previously been linked to anthelmintic resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Helmintíase/diagnóstico , Helmintíase/tratamento farmacológico , Solo/parasitologia , Administração Oral , Albendazol/administração & dosagem , Animais , Brasil , Criança , Testes Diagnósticos de Rotina/métodos , Etiópia , Fezes/parasitologia , Feminino , Helmintos/genética , Humanos , Laos , Masculino , Contagem de Ovos de Parasitas/métodos , Sensibilidade e Especificidade , Tanzânia , Tubulina (Proteína)/genética , Organização Mundial da Saúde
5.
BMC Infect Dis ; 19(1): 659, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340774

RESUMO

BACKGROUND: It is estimated that over a third of the world population is infected by malaria and helminthiases mainly among communities with high poverty indices. The distribution of these parasitic infections overlaps in many epidemiological settings and have varying outcomes in the host. In this paper we report the prevalence of malaria and intestinal helminthiases coinfections among malaria suspected patients and the association of helminthiases with the occurrence of malaria and its outcomes in Wondo Genet, southern Ethiopia. METHODS: In a cross-sectional study conducted from December 2009 to July 2010 in Kella, Aruma and Busa Health Centers in Wondo Genet, a total of 427 consenting febrile patients were screened for malaria and intestinal helminths infections. Malaria parasite detection and quantification were done using Giemsa stained thick and thin blood films. Helminth infections were screened and quantified by Kato-Katz thick smear method. Haemoglobin level was assessed using haemocue machine (HemoCue HB 201+). Difference in proportions and means were tested by Student's t test and ANOVA while logistic regression analysis was used to determine the association between variables. RESULTS: Of the total examined, 196 (45.90%) were positive for at least one helminth infection while 276 (64.64%) were positive for malaria. The prevalence of Plasmodium falciparum and P. vivax infections were 47.31 and 16.62%, respectively. The most common helminth parasites detected were Ascaris lumbricoides (33.96%), Trichuris trichiura (21.55%), Schistosoma mansoni (13.35%), and hookworms (6.79%). The overall malaria-helminthiases coinfection was 33.96%. The prevalence of anaemia was 43.12%. Helminthiases coinfection showed a positive correlation with the occurrence of malaria (AOR = 2.17, 95% CI: 1.44-3.28; P < 0.001). Schistosoma mansoni coinfection was associated with the increased risk of developing malaria associated anaemia (OR = 14.4, 95% CI: 1.37-150.80; P = 0.026). CONCLUSION: Malaria and helminth coinfections are important causes of morbidities among the population in Wondo Genet necessitating integrated control measures. Nevertheless, further detailed studies on the consequences and pathogenesis of these coinfections are needed to institute sound control and intervention measures.


Assuntos
Coinfecção/epidemiologia , Helmintíase/epidemiologia , Enteropatias Parasitárias/epidemiologia , Malária/epidemiologia , Adolescente , Adulto , Idoso , Animais , Criança , Coinfecção/parasitologia , Coinfecção/prevenção & controle , Comorbidade , Estudos Transversais , Etiópia/epidemiologia , Feminino , Febre/epidemiologia , Febre/parasitologia , Helmintíase/parasitologia , Helmintíase/prevenção & controle , Helmintos/genética , Helmintos/isolamento & purificação , Humanos , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/prevenção & controle , Malária/parasitologia , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Prevalência , Viverridae , Adulto Jovem
6.
Parasit Vectors ; 12(1): 349, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300009

RESUMO

BACKGROUND: Four species of Strongyloides, Strongyloides felis, Strongyloides planiceps, Strongyloides stercoralis and Strongyloides tumefaciens, have been identified in cats based on morphology and location in the host with limited data on the prevalence and disease potential of these different species. Strongyloides tumefaciens adults are located in colonic nodules while the other three species are in the small intestine. The literature on Strongyloides in cats is scattered and has never been compiled. The aim of this article is to provide a short review of the existing literature on Strongyloides spp. in cats, to describe the pathology of colonic nodules containing Strongyloides sp. seen at necropsies of cats in St. Kitts, West Indies, and to provide the first unequivocal report of zoonotic S. stercoralis in cats based on sequencing analysis of a portion of the cytochrome c oxidase subunit 1 (cox1) gene, and supported by phylogenetic analysis. RESULTS: Colonic nodules containing sections of nematodes, histologically compatible with Strongyloides sp. were seen during necropsy in six cats in St. Kitts, West Indies. Sequencing of the cox1 gene of the mitochondrial DNA extracted from colonic nodules from two of these cats matched sequences of the zoonotic strain of S. stercoralis. CONCLUSIONS: The morphological similarities between S. stercoralis-associated colonic nodules and previous reports of S. tumefaciens, together with the insufficient defining criteria for S. tumefaciens raises questions about the validity of the species. Further sampling and genetic characterization of isolates is needed to understand the species in cats and their zoonotic potential.


Assuntos
Gatos/parasitologia , Colo/patologia , Hiperplasia/parasitologia , Estrongiloidíase/veterinária , Zoonoses/parasitologia , Animais , Colo/citologia , Colo/parasitologia , DNA Mitocondrial/genética , DNA Ribossômico/genética , Fezes/parasitologia , Helmintos/genética , Filogenia , RNA Ribossômico 18S/genética , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/epidemiologia , Índias Ocidentais , Zoonoses/patologia
7.
Nucleic Acids Res ; 47(13): 6858-6870, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31194871

RESUMO

Inverted repeats are common DNA elements, but they rarely overlap with protein-coding sequences due to the ensuing conflict with the structure and function of the encoded protein. We discovered numerous perfect inverted repeats of considerable length (up to 284 bp) embedded within the protein-coding genes in mitochondrial genomes of four Nematomorpha species. Strikingly, both arms of the inverted repeats encode conserved regions of the amino acid sequence. We confirmed enzymatic activity of the respiratory complex I encoded by inverted repeat-containing genes. The nucleotide composition of inverted repeats suggests strong selection at the amino acid level in these regions. We conclude that the inverted repeat-containing genes are transcribed and translated into functional proteins. The survey of available mitochondrial genomes reveals that several other organisms possess similar albeit shorter embedded repeats. Mitochondrial genomes of Nematomorpha demonstrate an extraordinary evolutionary compromise where protein function and stringent secondary structure elements within the coding regions are preserved simultaneously.


Assuntos
Genes de Helmintos/genética , Genes Mitocondriais/genética , Código Genético , Genoma Mitocondrial , Helmintos/genética , Sequências Repetidas Invertidas/genética , Sequência de Aminoácidos , Animais , Composição de Bases , Sequência de Bases , DNA de Helmintos/genética , DNA Ribossômico/genética , Complexo I de Transporte de Elétrons/genética , Evolução Molecular , Feminino , Proteínas de Helminto/genética , Masculino , Consumo de Oxigênio , RNA de Helmintos/genética , RNA Ribossômico 18S/genética , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
8.
Acta Parasitol ; 64(3): 625-637, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31165986

RESUMO

INTRODUCTION: This is the first worldwide systematic and quantitative study to count and identify helminth parasites from 100 blue and 44 fin whale fecal samples collected in the Gulf of California during winter (1993-2014). RESULTS: Blue and fin whale feces had similar prevalence of adult acanthocephalans (Bolbosoma sp.) in feces (18.2% and 14.6%, respectively), but blue whales had significantly higher helminth egg prevalence in feces (100%) and mean intensity (443 ± 318 eggs/g) compared to fin whales (61%, 252 ± 327 eggs/g). Diphyllobothrium sp. eggs were identified in blue whale feces and Diphyllobothridae, Ogmogaster sp. and Crassicauda sp. eggs were identified in fin whale feces. We tested the hypothesis that egg intensity in blue whale's feces varies as a function of age class, reproductive status, sex, preservation and sampling years using a Generalized Linear Model. This model explained 61% of the variance in the helminth egg intensity, but it was not significant. Eighteen blue whale individuals were resampled over time without significant difference between consecutive samples. CONCLUSIONS: Thus, all individual blue whales that migrate to the Gulf of California during winter are permanently parasitized with helminths, while the resident fin whales showed lower prevalence and intensity. This helminth load difference is likely due to their different diets duringsummer-fall, when blue whales feed on other krill species in the California Current System and fin whales shift to school fish prey types in the Gulf of California.


Assuntos
Fezes/parasitologia , Baleia Comum/parasitologia , Helmintíase Animal/parasitologia , Helmintos/isolamento & purificação , Migração Animal , Animais , Balaenoptera/parasitologia , Balaenoptera/fisiologia , Feminino , Baleia Comum/fisiologia , Helmintíase Animal/fisiopatologia , Helmintos/classificação , Helmintos/genética , Helmintos/fisiologia , Masculino , Reprodução , Estações do Ano
9.
PLoS Negl Trop Dis ; 13(6): e0007363, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31206520

RESUMO

Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished conditions and limited access to public health systems. Underestimation of infection prevalence using traditional microscopy-based diagnostic techniques is common, specifically in populations with access to benzimidazole mass treatment programs and a predominance of low intensity infections. In this study, we developed a multiplexed-tandem qPCR (MT-PCR) tool to identify and quantify STH eggs in stool samples. We have assessed this assay by measuring infection prevalence and intensity in field samples of two cohorts of participants from Timor-Leste and Cambodia, which were collected as part of earlier epidemiological studies. MT-PCR diagnostic parameters were compared to a previously published multiplexed qPCR for STH detection. The MT-PCR assay agreed strongly with qPCR data and showed a diagnostic specificity of 99.60-100.00% (sensitivity of 83.33-100.00%) compared to qPCR and kappa agreement exceeding 0.85 in all tests. In addition, the MT-PCR has the added advantage of distinguishing Ancylostoma spp. species, namely Ancylostoma duodenale and Ancylostoma ceylanicum. This semi-automated platform uses a standardized, manufactured reagent kit, shows excellent run-to-run consistency/repeatability and supports high-throughput detection and quantitation at a moderate cost.


Assuntos
Fezes/parasitologia , Helmintíase/diagnóstico , Helmintos/isolamento & purificação , Enteropatias Parasitárias/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Camboja , Criança , Pré-Escolar , Feminino , Helmintos/classificação , Helmintos/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Timor-Leste , Adulto Jovem
10.
BMC Genomics ; 20(1): 333, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046663

RESUMO

BACKGROUND: Helminth infections affect ~ 60% of the human population that lives in tropical and subtropical regions worldwide. These infections result in diseases like schistosomiasis, lymphatic filariasis, river blindness and echinococcosis. Here we provide a comprehensive computational analysis of the aminoacyl tRNA synthetase (aaRS) enzyme family from 27 human-infecting helminths. Our analyses support the idea that several helminth aaRSs can be targeted for drug repurposing or for development of new drugs. For experimental validation, we focused on Onchocerciasis (also known as "river blindness"), a filarial vector-borne disease that is prevalent in Africa and Latin America. We show that halofuginone (HF) can act as a potent inhibitor of Onchocerca volvulus prolyl tRNA synthetase (OvPRS). RESULTS: The conserved enzyme family of aaRSs has been validated as druggable targets in numerous eukaryotic parasites. We thus embarked on assessing aaRSs from the genomes of 27 helminths that cause infections in humans. In order to delineate the distribution of aaRSs per genome we utilized Hidden Markov Models of aaRS catalytic domains to identify all orthologues. We note that Fasciola hepatica genome encodes the highest number of aaRS-like proteins (69) whereas Taenia asiatica has the lowest count (32). The number of genes for any particular aaRS-like protein varies from 1 to 8 in these 27 studied helminths. Sequence alignments of helminth-encoded lysyl, prolyl, leucyl and threonyl tRNA synthetases suggest that various known aaRS inhibitors like Cladosporin, Halofuginone, Benzoborale and Borrelidin may be of utility against helminths. The recombinantly expressed Onchocerca volvulus PRS was used as proof of concept for targeting aaRS with drug-like molecules like HF. CONCLUSIONS: Systematic analysis of unique subdomains within helminth aaRSs reveals the presence of a number of non-canonical domains like PAC3, Utp-14, Pex2_Pex12 fused to catalytic domains in the predicted helminth aaRSs. We have established a platform for biochemical validation of a large number of helminth aaRSs that can be targeted using available inhibitors to jump-start drug repurposing against human helminths.


Assuntos
Aminoacil-tRNA Sintetases/genética , Genoma Helmíntico , Genômica/métodos , Proteínas de Helminto/genética , Helmintíase/genética , Helmintos/genética , Helmintos/isolamento & purificação , Animais , Helmintíase/parasitologia , Helmintos/classificação , Humanos , Filogenia
11.
PLoS Negl Trop Dis ; 13(5): e0007406, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083673

RESUMO

BACKGROUND: The World Health Organization has recently reemphasized the importance of providing preventive chemotherapy to women of reproductive age in countries endemic for soil-transmitted helminthiasis as they are at heightened risk of associated morbidity. The Demographic and Health Surveys (DHS) Program is responsible for collecting and disseminating accurate, nationally representative data on health and population in developing countries. Our study aims to estimate the number of pregnant women at risk of soil-transmitted helminthiasis that self-reported deworming by antenatal services in endemic countries that conducted Demographic and Health Surveys. METHODOLOGY/PRINCIPAL FINDINGS: The number of pregnant women living in endemic countries was extrapolated from the United Nations World Population Prospects 2015. National deworming coverage among pregnant women were extracted from Demographic and Health Surveys and applied to total numbers of pregnant women in the country. Sub-national DHS with data on self-reported deworming were available from 49 of the 102 endemic countries. In some regions more than 73% of STH endemic countries had a DHS. The DHS report an average deworming coverage of 23% (CI 19-28), ranging from 2% (CI 1-3) to 35% (CI 29-40) in the different regions, meaning more than 16 million pregnant women were dewormed in countries surveyed by DHS. The deworming rates amongst the 43 million pregnant women in STH endemic countries not surveyed by DHS remains unknown. CONCLUSIONS/SIGNIFICANCE: These estimates will serve to establish baseline numbers of deworming coverage among pregnant women, monitor progress, and urge endemic countries to continue working toward reducing the burden of soil-transmitted helminthiasis. The DHS program should be extended to STH-endemic countries currently not covering the topic of deworming during pregnancy.


Assuntos
Anti-Helmínticos/uso terapêutico , Helmintíase/tratamento farmacológico , Helmintos/isolamento & purificação , Complicações Parasitárias na Gravidez/tratamento farmacológico , Solo/parasitologia , Adulto , África/epidemiologia , Animais , Ásia/epidemiologia , Doenças Endêmicas/prevenção & controle , Feminino , Helmintíase/epidemiologia , Helmintos/classificação , Helmintos/genética , Humanos , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Autorrelato , América do Sul/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-31125837

RESUMO

Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in 'refugia', unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of refugia-based approaches to slow the development of drug resistance in parasitic helminths is currently limited. Moreover, the conditions needed for refugia to work, or how transferable those are between parasite-host systems, are not known. This review, born of an international workshop, seeks to deconstruct the concept of refugia and examine its assumptions and applicability in different situations. We conclude that factors potentially important to refugia, such as the fitness cost of drug resistance, the degree of mixing between parasite sub-populations selected through treatment or not, and the impact of parasite life-history, genetics and environment on the population dynamics of resistance, vary widely between systems. The success of attempts to generate refugia to limit anthelmintic drug resistance are therefore likely to be highly dependent on the system in hand. Additional research is needed on the concept of refugia and the underlying principles for its application across systems, as well as empirical studies within systems that prove and optimise its usefulness.


Assuntos
Anti-Helmínticos/farmacologia , Resistência a Medicamentos , Helmintos/efeitos dos fármacos , Animais , Helmintíase/parasitologia , Helmintos/genética , Helmintos/crescimento & desenvolvimento , Humanos , Refúgio de Vida Selvagem
13.
PLoS Negl Trop Dis ; 13(5): e0007323, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050672

RESUMO

BACKGROUND: Soil transmitted helminths (STH) infect >1.5 billion people. Mass drug administration (MDA) effectively reduces infection; however, there is evidence for rapid reinfection and risk of potential drug resistance. We conducted a randomized controlled trial in Bangladesh (WASH Benefits, NCT01590095) to assess whether water, sanitation, hygiene and nutrition interventions, alone and combined, reduce STH in a setting with ongoing MDA. METHODOLOGY/PRINCIPAL FINDINGS: In 2012-2013, we randomized 720 clusters of 5551 pregnant women into water treatment, sanitation, handwashing, combined water+sanitation+handwashing (WSH), nutrition, nutrition+WSH (N+WSH) or control arms. In 2015-2016, we enrolled 7795 children, aged 2-12 years, of 4102 available women for STH follow-up and collected stool from 7187. We enumerated STH infections with Kato-Katz. We estimated intention-to-treat intervention effects on infection prevalence and intensity. Participants and field staff were not blinded; laboratory technicians and data analysts were blinded. Prevalence among controls was 36.8% for A. lumbricoides, 9.2% for hookworm and 7.5% for T. trichiura. Most infections were low-intensity. Compared to controls, the water intervention reduced hookworm by 31% (prevalence ratio [PR] = 0.69 (0.50,0.95), prevalence difference [PD] = -2.83 (-5.16,-0.50)) but did not affect other STH. Sanitation improvements reduced T. trichiura by 29% (PR = 0.71 (0.52,0.98), PD = -2.17 (-4.03,-0.38)), had a similar borderline effect on hookworm and no effect on A. lumbricoides. Handwashing and nutrition interventions did not reduce any STH. WSH and N+WSH reduced hookworm prevalence by 29-33% (WSH: PR = 0.71 (0.52,0.99), PD = -2.63 (-4.95,-0.31); N+WSH: PR = 0.67 (0.50,0.91), PD = -3.00 (-5.14,-0.85)) and marginally reduced A. lumbricoides. Effects on infection intensity were similar. CONCLUSIONS/SIGNIFICANCE: In a low-intensity infection setting with MDA, we found modest but sustained hookworm reduction from water treatment and combined WSH interventions. Impacts were more pronounced on STH species with short vs. long-term environmental survival. Our findings suggest possible waterborne transmission for hookworm. Water treatment and sanitation improvements can augment MDA to interrupt STH transmission. TRIAL REGISTRATION: NCT01590095.


Assuntos
Água Doce/parasitologia , Desinfecção das Mãos/métodos , Helmintíase/prevenção & controle , Helmintos/isolamento & purificação , Saneamento/métodos , Animais , Bangladesh/epidemiologia , Criança , Pré-Escolar , Dieta , Fezes/parasitologia , Feminino , Helmintíase/epidemiologia , Helmintíase/transmissão , Helmintos/classificação , Helmintos/genética , Humanos , Masculino , Avaliação Nutricional , Gestantes , Solo/parasitologia
14.
Nat Rev Genet ; 20(6): 341-355, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30918369

RESUMO

Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.


Assuntos
Doenças Transmissíveis/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Ciência de Laboratório Médico/métodos , Metagenoma , Metagenômica/métodos , Animais , Antibacterianos/uso terapêutico , Bactérias/genética , Bactérias/isolamento & purificação , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , DNA/genética , DNA/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Fungos/genética , Fungos/isolamento & purificação , Helmintos/genética , Helmintos/isolamento & purificação , Interações Hospedeiro-Patógeno , Humanos , Ciência de Laboratório Médico/instrumentação , Metagenômica/instrumentação , Saúde Pública/tendências , Vírus/genética , Vírus/isolamento & purificação
15.
J Helminthol ; 94: e30, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30714552

RESUMO

The black rat Rattus rattus and the house mouse Mus musculus are two commensal rodent species that harbour and shed zoonotic pathogens, including helminths. The aim of this survey was to study the helminth community and the patterns of infections in R. rattus and M. musculus from two Mayan communities in Mexico. Gastrointestinal helminths were isolated from 322 M. musculus and 124 R. rattus, including Gongylonema neoplasticum, Hassalstrongylus aduncus, Hassalstrongylus musculi, Hydatigera taeniaeformis metacestode, Hymenolepis diminuta, Nippostrongylus brasiliensis, Oligacanthorhynchidae gen. sp., Syphacia muris, Syphacia obvelata, Rodentolepis microstoma and Trichuris muris. The overall richness of helminths was seven in R. rattus and six in M. musculus. The results of generalized linear models showed that juvenile rodents had lower probabilities of being infected with G. neoplasticum, H. taeniaeformis and H. musculi than adult rodents. A positive association between the prevalence of S. muris and rat abundance was found. The intensity of infection with S. muris was higher in the rainy season than in the dry season; the opposite result was found for H. musculi infection. Male R. rattus harboured more S. muris specimens. The intensity of infection with T. muris was inversely associated with mouse abundance. The presence of the zoonotic H. diminuta, as well as H. taeniaeformis and R. microstoma in rodent populations indicates that there is risk of transmission, and that their entire life cycle occurs in the study area.


Assuntos
Helmintíase Animal/parasitologia , Helmintos/isolamento & purificação , Doenças dos Roedores/parasitologia , Animais , Feminino , Trato Gastrointestinal/parasitologia , Helmintíase Animal/epidemiologia , Helmintos/classificação , Helmintos/genética , Masculino , México/epidemiologia , Camundongos , Prevalência , Ratos , Estações do Ano
16.
J Helminthol ; 94: e37, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30767800

RESUMO

The European badger (Meles meles) is Ireland's largest terrestrial carnivore. Since first being identified as a wildlife reservoir of bovine tuberculosis in 1974 there has been an increased research focus into the behaviour of these ecologically important mammals in the Republic of Ireland (ROI). However, to date there has never been an assessment of the helminth parasite community of Irish badgers. This study of 289 badgers found helminth infection to be endemic within the sample population and we report for the first time the prevalence, abundance, intensity and aggregation of helminth infection in ROI. Eight distinct helminth taxa were recorded: Aelurostrongylus falciformis, Crenosoma melesi, Eucoleus aerophilus, Species A, Strongyloides spp., Uncinaria criniformis, and two unidentifiable but morphologically distinct nematodes. All helminths belong to the taxon Nematoda, and this is the first report of an exclusively nematode community across the badger's Eurasian distribution. Infection was not significantly influenced by the host sex, region of origin or season of sampling.


Assuntos
Animais Selvagens/parasitologia , Helmintos/isolamento & purificação , Mustelidae/parasitologia , Animais , Feminino , Helmintos/classificação , Helmintos/genética , Irlanda , Masculino
17.
Trends Parasitol ; 35(4): 289-301, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30733094

RESUMO

The rapid evolution of anthelmintic resistance in a number of parasites of livestock and domesticated animals has occurred in response to widespread use of anthelmintics for parasite control, and threatens the success of parasite control of species that infect humans. The genetic basis of resistance to most anthelmintics remains poorly resolved. Genome-wide approaches are now accessible due to recent advances in high-throughput sequencing, and are increasingly applied to characterize traits including drug resistance. Here, we discuss why traditional candidate gene studies have largely failed to define the genetics of resistance, and why - and in what circumstances - we expect genome-wide approaches to shed new light on the modes of action and the evolution of resistance to anthelmintic compounds.


Assuntos
Anti-Helmínticos/farmacologia , Resistência a Medicamentos/genética , Genoma Helmíntico/genética , Estudo de Associação Genômica Ampla , Helmintos/efeitos dos fármacos , Helmintos/genética , Animais
18.
Mol Genet Genomics ; 294(2): 469-478, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30604069

RESUMO

Anthocyanins are a class of pigments ubiquitously distributed in plants and play roles in adoption to several stresses. The red plant gene (R1) promotes light-induced anthocyanin accumulation and red/purple pigmentation in cotton. Using 11 markers developed via genome resequencing, the R1 gene was located in an interval of approximately 136 kb containing three annotated genes. Among them, a PAP1 homolog, GhPAP1D (Gohir.D07G082100) displayed differential transcript level in the red- and green-plant leaves. GhPAP1D encoded a R2R3-MYB transcription factor and its over-expression resulted in increased anthocyanin accumulation in transgenic tobaccos and cottons. Dual luciferase assay indicated that GhPAP1D activated the promoters of several cotton anthocyanin structural genes in tobacco leaves. Importantly, we found that the GhPAP1D-overexpressing cotton leaves had increased resistance to both bollworm and spite mite. Our data demonstrated that GhPAP1D was the controlling gene of the red plant phenotype in cotton, and as the major anthocyanin regulator, this gene was potential to create transgenic cottons with resistance to a broad spectrum of herbivores.


Assuntos
Antocianinas/genética , Resistência à Doença/genética , Gossypium/genética , Folhas de Planta/genética , Animais , Antocianinas/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Gossypium/crescimento & desenvolvimento , Helmintos/genética , Controle Biológico de Vetores , Pigmentação/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/parasitologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/parasitologia , Regiões Promotoras Genéticas , Tetranychidae/genética , Tetranychidae/patogenicidade
19.
Nat Genet ; 51(1): 163-174, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30397333

RESUMO

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms.


Assuntos
Helmintos/genética , Animais , Genoma/genética , Genômica/métodos , Humanos , Nematoides/genética , Filogenia
20.
J Helminthol ; 93(6): 720-731, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30220264

RESUMO

Among the Brazilian marsupials, the species of the genus Didelphis are the most parasitized by helminths. This study aimed to describe the species composition and to analyse the helminth communities of the Atlantic Forest common opossum Didelphis aurita at infracommunity and component community levels using the Elements of Metacommunity Structure Analysis, considering peri-urban, sylvatic and rural environments in the state of Rio de Janeiro, Brazil. Seventy-three specimens of D. aurita were captured during the study. Fourteen species of helminths were collected: nine of the phylum Nematoda (Trichuris minuta, Trichuris didelphis, Globocephalus marsupialis, Heterostrongylus heterostrongylus, Travassostrongylus orloffi, Viannaia hamata, Aspidodera raillieti, Cruzia tentaculata and Turgida turgida); four of the phylum Platyhelminthes (three species of Trematoda, Duboisiella proloba, Brachylaima advena and Rhopalias coronatus, and one species of the class Cestoda); and one species of the phylum Acanthocephala (Oligacanthorhynchus microcephalus). More than 95% of the animals were infected with parasites. The most abundant parasite species were V. hamata, T. turgida, C. tentaculata and T. orloffi. The nematodes T. turgida, C. tentaculata and A. raillieti were the most dominant species in the three environments. The analysis of the metacommunity structure indicated a structured pattern as a function of the environmental gradient, but only when all localities were considered together. At the infracommunity and component community levels, quasi-nested and nested structures with stochastic species loss were observed, respectively. The results indicate that the settlement of helminth species in the opossums can be attributed to the heterogeneity among individual hosts in relation to their exposure to parasites and to extrinsic factors, which vary among habitats, considering a regional scale. On a local scale, the characteristics of this host species may promote homogenization among individual hosts in terms of their exposure to the helminths. This study constitutes a new host record for the species G. marsupialis and T. didelphis and represents a pioneering investigation of the helminth metacommunity of a Neotropical marsupial.


Assuntos
Didelphis/parasitologia , Helmintíase Animal/parasitologia , Helmintos/isolamento & purificação , Animais , Brasil , Feminino , Helmintos/classificação , Helmintos/genética , Helmintos/fisiologia , Especificidade de Hospedeiro , Masculino , População Rural
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