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PLoS Neglected Tropical Diseases Apr 2019Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide...
BACKGROUND
Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit.
METHODOLOGY/PRINCIPAL FINDINGS
We investigated the vaccine efficacy in outbred Syrian hamsters of three A. ceylanicum hookworm antigen candidates from two classes of proteins previously identified as promising vaccine candidates. These include two intestinally-enriched, putatively secreted cathepsin B cysteine proteases (AceyCP1, AceyCPL) and one small Kunitz-type protease inhibitor (AceySKPI3). Recombinant proteins were produced in Pichia pastoris, and adsorbed to Alhydrogel. Recombinant AceyCPL (rAceyCPL)/Alhydrogel and rAceySKPI3/Alhydrogel induced high serum immunoglobulin G (IgG) titers in 8/8 vaccinates, but were not protective. rAceyCP1/Alhydrogel induced intermediate serum IgG titers in ~60% of vaccinates in two different trials. rAceyCP1 serum IgG responders had highly significantly decreased hookworm burdens, fecal egg counts and clinical pathology compared to Alhydrogel controls and nonresponders. Protection was highly correlated with rAceyCP1 serum IgG titer. Antisera from rAceyCP1 serum IgG responders, but not nonresponders or rAceyCPL/Alhydrogel vaccinates, significantly reduced adult A. ceylanicum motility in vitro. Furthermore, rAceyCP1 serum IgG responders had canonical Th2-specific recall responses (IL4, IL5, IL13) in splenocytes stimulated ex vivo.
CONCLUSIONS/SIGNIFICANCE
These findings indicate that rAceyCP1 is a promising vaccine candidate and validates a genomic/transcriptomic approach to human hookworm vaccine discovery.
Topics: Amino Acid Sequence; Ancylostoma; Ancylostomiasis; Animals; Antibodies, Helminth; Antigens, Helminth; Antigens, Surface; Cysteine Proteases; Disease Models, Animal; Immunoglobulin G; Intestinal Diseases, Parasitic; Male; Mesocricetus; Recombinant Proteins; Vaccination; Vaccines; Vaccines, Synthetic
PubMed: 31009474
DOI: 10.1371/journal.pntd.0007345 -
The Korean Journal of Parasitology Feb 2019Melting temperature shift (Tm-shift) is a new detection method that analyze the melting curve on real-time PCR thermocycler using SYBR Green I fluorescent dye. To...
Melting temperature shift (Tm-shift) is a new detection method that analyze the melting curve on real-time PCR thermocycler using SYBR Green I fluorescent dye. To establish a Tm-shift method for the detection of Ancylostoma ceylanicum and A. tubaeforme in cats, specific primers, with GC tail of unequal length attached to their 5 ́ end, were designed based on 2 SNP loci (ITS101 and ITS296) of the internal transcribed spacer 1 (ITS1) sequences. The standard curve of Tm-shift was established using the standard plasmids of A. ceylanicum (AceP) and A. tubaeforme (AtuP). The Tm-shift method stability, sensitivity, and accuracy were tested with reference to the standard curve, and clinical fecal samples were also examined. The results demonstrated that the 2 sets of primers based on the 2 SNPs could accurately distinguish between A. ceylanicum and A. tubaeforme. The coefficient of variation (CV) of Tm-values of AceP and AtuP was 0.07% and 0.06% in ITS101 and was 0.06% and 0.08% in ITS296, respectively. The minimum detectable DNA concentration was 5.22×10-6 and 5.28×10-6 ng/μl samples of AceP and AtuP, respectively. The accuracy of Tm-shift method reached 100% based on examination of 10 hookworm DNA samples with known species. In the clinical detection of hookworm in 69 stray cat fecal sample, the Tm-shift detection results were consistent with the microscopic examination and successfully differentiated between the 2-hookworm species. In conclusion, the developed method is a rapid, sensitive and accurate technique and can provide a promising tool for clinical detection and epidemiological investigation of cat-derived hookworms.
Topics: Ancylostoma; Ancylostomiasis; Animals; Cat Diseases; Cats; DNA Primers; DNA, Helminth; DNA, Ribosomal Spacer; Feces; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Transition Temperature
PubMed: 30840793
DOI: 10.3347/kjp.2019.57.1.9 -
Veterinary Parasitology Jun 2019A new topical formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus, Zoetis) was evaluated in the treatment and control of naturally occurring...
Efficacy and safety of a new topical formulation of selamectin plus sarolaner in the treatment and control of natural infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States.
A new topical formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus, Zoetis) was evaluated in the treatment and control of naturally occurring infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States. Three thousand three hundred three (3303) cats were screened in 25 veterinary practices in 15 states and 153 hookworm-positive cats (A. tubaeforme and/or A. braziliense), mainly from Alabama, Mississippi, Texas, and Hawaii, were identified; 135 cats met all the criteria for enrollment and were included on study. The cats were randomly assigned to treatment with Revolution (at the label dosage, to provide a minimum dosage of 6 mg/kg selamectin) or selamectin plus sarolaner (at a dosage of 6-12 mg/kg plus 1-2 mg/kg, respectively). Treatments were administered at the time of enrollment and repeated 30 days later. Fecal samples were collected for differential fecal egg count prior to the first treatment (Day 0), prior to the second treatment (Day 30), and approximately 30 days later (Day 60). Efficacy was based on the percentage reductions in geometric mean fecal egg count for A. tubaeforme on Day 30 and Day 60 compared with Day 0. Where cats were co-infected with T. cati, efficacy against this species was also evaluated. Efficacy data were evaluated for A. tubaeforme for 40 cats on both Day 30 and Day 60 for the group treated with the selamectin/sarolaner combination and reductions in geometric mean fecal egg counts of 99.4% and 99.7% were demonstrated for Day 30 and Day 60, respectively. For the group treated with selamectin alone, 44 and 40 cats were evaluated and percent reductions for Day 30 and Day 60 were 99.5% and 99.9%, respectively. For T. cati, 14 cats were evaluated in the selamectin/sarolaner-treated group for Day 30 and for Day 60, and the reduction in geometric mean fecal egg count was 100% for both days. There were 11 and 9 cats evaluated for Day 30 and Day 60, respectively, for the selamectin-treated group and the reduction was again 100% for both days. The geometric mean fecal egg counts post-treatment were significantly lower than pre-treatment for both A. tubaeforme and T. cati, for both treatments, and for both periods of interest (P < 0.0001). No serious adverse events related to treatment with either product occurred during the study. Thus, both selamectin alone and the combination product of selamectin/sarolaner were safe and effective when administered on a monthly basis for the treatment and control of natural infections of A. tubaeforme and T. cati. The addition of sarolaner to the formulation did not interfere with the efficacy of selamectin against these nematodes.
Topics: Ancylostoma; Ancylostomiasis; Animals; Antiparasitic Agents; Azetidines; Cat Diseases; Cats; Female; Ivermectin; Male; Random Allocation; Spiro Compounds; Toxocara; Toxocariasis; Treatment Outcome; United States
PubMed: 30470638
DOI: 10.1016/j.vetpar.2018.10.012 -
International Journal For Parasitology.... Dec 2018Infection with gastrointestinal parasitic nematodes is a major cause of chronic morbidity and economic burden around the world, particularly in low-resource settings.... (Review)
Review
Infection with gastrointestinal parasitic nematodes is a major cause of chronic morbidity and economic burden around the world, particularly in low-resource settings. Some parasitic nematode species, including the human-parasitic threadworm Strongyloides stercoralis and human-parasitic hookworms in the genera Ancylostoma and Necator, feature a soil-dwelling infective larval stage that seeks out hosts for infection using a variety of host-emitted sensory cues. Here, we review our current understanding of the behavioral responses of soil-dwelling infective larvae to host-emitted sensory cues, and the molecular and cellular mechanisms that mediate these responses. We also discuss the development of methods for transgenesis and CRISPR/Cas9-mediated targeted mutagenesis in Strongyloides stercoralis and the closely related rat parasite Strongyloides ratti. These methods have established S. stercoralis and S. ratti as genetic model systems for gastrointestinal parasitic nematodes and are enabling more detailed investigations into the neural mechanisms that underlie the sensory-driven behaviors of this medically and economically important class of parasites.
Topics: Ancylostoma; Ancylostomiasis; Animals; Gastrointestinal Diseases; Host-Parasite Interactions; Humans; Larva; Necator; Nematoda; Nematode Infections; Rats; Sensation; Soil; Strongyloides ratti; Strongyloides stercoralis
PubMed: 30396862
DOI: 10.1016/j.ijpddr.2018.10.008 -
Journal of Clinical Laboratory Analysis Mar 2019Our aim intended to determine the relationship between hematological parameters (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and...
OBJECTIVE
Our aim intended to determine the relationship between hematological parameters (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and eosinophil-to-lymphocyte ratio [ELR]) and ancylostomiasis.
METHODS
There were 140 patients with ancylostomiasis and 159 healthy controls enrolled in this study. All data were collected from electronic medical records of the First Affiliated Hospital of Guangxi Medical University.
RESULTS
The levels of NLR, PLR, and ELR in ancylostomiasis patients were significantly higher than those in the healthy controls (all P = 0.000). A receiver operating characteristic curve was generated to assess the diagnostic efficacy of these three hematological parameters. ELR (AUC = 0.850; sensitivity = 75.00%; specificity = 86.80%) showed the superior AUC than those of NLR (AUC = 0.718; sensitivity = 53.57%; specificity = 88.68%) and PLR (AUC = 0.806; sensitivity = 68.57%; specificity = 86.79%), respectively. A multivariate regression model using the two selected indices (RBC and ELR) was established with the model's sensitivity and specificity reached 82.86% and 96.23%, respectively. In the ancylostomiasis patient group, NLR (r = -0.452, P = 0.000) and PLR (r = -0.357, P = 0.000) were reversely associated with eosinophils.
CONCLUSION
The pretreatment levels of the three hematological parameters (NLR, PLR, and ELR) may serve as valuable indicators for distinguishing patients with ancylostomiasis from healthy controls. NLR and PLR are negatively associated with the previous indicator, eosinophils.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ancylostomiasis; Area Under Curve; Child; Child, Preschool; Eosinophils; Female; Humans; Infant; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Retrospective Studies; Young Adult
PubMed: 30390342
DOI: 10.1002/jcla.22705 -
World Journal of Gastroenterology Sep 2018To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia. (Meta-Analysis)
Meta-Analysis Review
AIM
To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia.
METHODS
A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in PubMed, Google Scholar, Science Direct, World Health Organization African and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems.
RESULTS
Twenty-nine studies from Somalia and Somali immigrants (United Kingdom, United States, Italy, Libya) with a combined sample size for each type of viral hepatitis [hepatitis A virus (HAV): 1564, hepatitis B virus (HBV): 8756, hepatitis C virus (HCV): 6257, hepatitis D virus (HDV): 375 and hepatitis E virus (HEV): 278] were analyzed. The overall pooled prevalence rate of HAV was 90.2% (95%CI: 77.8% to 96%). The HAV prevalence among different age groups was as follows: < 1 year old, 61.54% (95%CI: 40.14% to 79.24%); 1-10 years old, 91.91% (95%CI: 87.76% to 94.73%); 11-19 years old, 96.31% (95%CI: 92.84% to 98.14%); 20-39 years old, 91.3% (95%CI: 83.07% to 95.73%); and > 40 years old, 86.96% (95%CI: 75.68% to 93.47%). The overall pooled prevalence of HBV was 18.9% (95%CI: 14% to 29%). The overall pooled prevalence among subgroups of HBV was 20.5% (95%CI: 5.1% to 55.4%) in pregnant women; 5.7% (95%CI: 2.7% to 11.5%) in children; 39.2% (95%CI: 33.4% to 45.4%) in patients with chronic liver disease, including hepatocellular carcinoma (HCC); 7.7% (95%CI: 4.2% to 13.6%), 12.4% (95%CI: 6.3% to 23.0%) and 11.8% (95%CI: 5.3% to 24.5%) in age groups < 20 years old, 20-39 years old and > 40 years old, respectively. The HBV prevalence among risk groups was 20% (95%CI: 7.19% to 44.64%) in female prostitutes, 21.28% (95%CI: 7.15% to 48.69%) in hospitalized adults, 5.56% (95%CI: 0.99% to 25.62%) in hospitalized children, 60% (95%CI: 31.66% to 82.92%) in patients with acute hepatitis, 33.55% (95%CI: 14.44% to 60.16%) in patients with ancylostomiasis, 12.34% (95%CI: 7.24% to 20.26%) in patients with leprosy and 20.19% (95%CI: 11.28% to 33.49%) in schistosomiasis patients. The overall pooled prevalence of HCV was estimated as 4.84% (95%CI: 3.02% to 7.67%). The prevalence rates among blood donors, risk groups, children and patients chronic liver disease (including HCC) was 0.87% (95%CI: 0.33% to 2.30%), 2.43% (95%CI: 1.21% to 4.8%), 1.37% (95%CI: 0.76% to 2.46%) and 29.82% (95%CI: 15.84% to 48.98%), respectively. The prevalence among genotypes of HCV was 21.9% (95%CI: 15.36% to 30.23%) in genotype 1, 0.87% (95%CI: 0.12% to 5.9%) in genotype 2, 25.21% (95%CI: 18.23% to 33.77%) in genotype 3, 46.24% (95%CI: 37.48% to 55.25%) in genotype 4, 2.52% (95%CI: 0.82% to 7.53%) in genotype 5, and 1.19% (95%CI: 0.07% to 16.38%) in genotype 6. The overall pooled prevalence of HDV was 28.99% (95%CI: 16.38% to 45.96%). The HDV prevalence rate among patients with chronic liver disease, including HCC, was 43.77% (95%CI: 35.09% to 52.84%). The overall pooled prevalence of HEV was 46.86% (95%CI: 5.31% to 93.28%).
CONCLUSION
Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease. This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.
Topics: Chronic Disease; Emigrants and Immigrants; Genotype; Hepatitis, Viral, Human; Humans; Italy; Libya; Prevalence; Somalia; United Kingdom; United States; Viruses
PubMed: 30228786
DOI: 10.3748/wjg.v24.i34.3927 -
The American Journal of Tropical... Nov 2018Hookworm disease caused by , , and affects half a billion people worldwide. The prevalence and intensity of infection of individual hookworm species are vital for...
Hookworm disease caused by , , and affects half a billion people worldwide. The prevalence and intensity of infection of individual hookworm species are vital for assessing morbidity and generating targeted intervention programs for their control. The present study aims to evaluate a multiplex real-time quantitative PCR (qPCR) assay to determine the prevalence and egg intensity of all three hookworm species and compare this with standard microscopy and published genus-based conventional and real-time multiplex qPCRs. Performance of the diagnostic assays was evaluated using DNA extracted from 192 fecal samples collected as part of a soil-transmitted helminth (STH) survey in northern Cambodia. The prevalence of hookworms as detected by the multiplex hookworm qPCR of 84/192 (43.8%) was significantly higher than that using microscopy of 49/192 (25.5%). The hookworm multiplex qPCR showed very good agreement for the detection of both (Kappa 0.943) and spp. (Kappa 0.936) with a multiplex STH qPCR. A strong and moderate quantitative correlation between cycle threshold and eggs per gram (EPG) feces was obtained for the hookworm qPCR for seeded DNA egg extracts ( ≥ 0.9004) and naturally egg-infected individuals ( = 0.6848), respectively. The newly developed hookworm quantitative multiplex qPCR has the potential for application in anthelmintic efficacy trials and for monitoring the success of mass deworming programs targeting individual species of anthroponotic and zoonotic hookworms.
Topics: Ancylostoma; Ancylostomiasis; Animals; Anthelmintics; Cambodia; Cross-Sectional Studies; DNA, Helminth; Feces; Hookworm Infections; Humans; Multiplex Polymerase Chain Reaction; Ovum; Parasite Egg Count; Prevalence
PubMed: 30226132
DOI: 10.4269/ajtmh.18-0276 -
Journal of Infection in Developing... Aug 2018Dogs may act as potential sources of zoonotic parasites, e.g. intestinal helminths like Toxocara spp., Ancylostoma spp., Echinococcus spp. In particular circumstances,...
INTRODUCTION
Dogs may act as potential sources of zoonotic parasites, e.g. intestinal helminths like Toxocara spp., Ancylostoma spp., Echinococcus spp. In particular circumstances, the environment contaminated by parasitic elements represents a source of infection for people and animals. The present study has evaluated the presence of zoonotic helminths in house dogs from central and north-eastern Italy.
METHODOLOGY
Stool samples from 493 dogs were examined by a qualitative copromicroscopic technique and differences in prevalence of zoonotic parasites were statistically examined in relation to canine individual data.
RESULTS
48/493 (9.7%) were positive for at least one parasite. Helminths recovered were Trichuris vulpis (5.5%), Toxocara canis (4.3%), Ancylostoma spp. (0.6%) and Eucoleus aerophilus (0.4%), while no cestodes were detected. Age and living with other dogs resulted risk factors for T. canis infection.
CONCLUSIONS
The health risk associated with the occurrence of parasitic nematodes in privately owned dogs, along with the current anthelmintic treatment plans, are discussed.
Topics: Ancylostomiasis; Animals; Dog Diseases; Dogs; Feces; Female; Italy; Male; Nematode Infections; Pets; Prevalence; Toxocariasis; Trichuriasis; Zoonoses
PubMed: 31958330
DOI: 10.3855/jidc.9865 -
Current Biology : CB Jul 2018Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are a major source of neglected tropical disease [1-6]. Their life cycle...
Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are a major source of neglected tropical disease [1-6]. Their life cycle includes an infective third-larval (iL3) stage that searches for hosts to infect in a poorly understood process that involves both thermal and olfactory cues. Here, we investigate the temperature-driven behaviors of skin-penetrating iL3s, including the human-parasitic threadworm Strongyloides stercoralis and the human-parasitic hookworm Ancylostoma ceylanicum. We show that human-parasitic iL3s respond robustly to thermal gradients. Like the free-living nematode Caenorhabditis elegans, human-parasitic iL3s show both positive and negative thermotaxis, and the switch between them is regulated by recent cultivation temperature [7]. When engaging in positive thermotaxis, iL3s migrate toward temperatures approximating mammalian body temperature. Exposing iL3s to a new cultivation temperature alters the thermal switch point between positive and negative thermotaxis within hours, similar to the timescale of thermal plasticity in C. elegans [7]. Thermal plasticity in iL3s may enable them to optimize host finding on a diurnal temperature cycle. We show that temperature-driven responses can be dominant in multisensory contexts such that, when thermal drive is strong, iL3s preferentially engage in temperature-driven behaviors despite the presence of an attractive host odorant. Finally, targeted mutagenesis of the S. stercoralis tax-4 homolog abolishes heat seeking, providing the first evidence that parasitic host-seeking behaviors are generated through an adaptation of sensory cascades that drive environmental navigation in C. elegans [7-10]. Together, our results provide insight into the behavioral strategies and molecular mechanisms that allow skin-penetrating nematodes to target humans.
Topics: Ancylostoma; Ancylostomiasis; Animals; Host-Seeking Behavior; Humans; Larva; Strongyloides stercoralis; Strongyloidiasis; Taxis Response; Thermosensing
PubMed: 30017486
DOI: 10.1016/j.cub.2018.05.063 -
Emerging Infectious Diseases Aug 2018During 2012-2015, US-bound refugees living in Myanmar-Thailand border camps (n = 1,839) were surveyed for hookworm infection and treatment response by using quantitative...
During 2012-2015, US-bound refugees living in Myanmar-Thailand border camps (n = 1,839) were surveyed for hookworm infection and treatment response by using quantitative PCR. Samples were collected at 3 time points: after each of 2 treatments with albendazole and after resettlement in the United States. Baseline prevalence of Necator americanus hookworm was 25.4%, Ancylostoma duodenale 0%, and Ancylostoma ceylanicum (a zoonosis) 5.4%. Compared with N. americanus prevalence, A. ceylanicum hookworm prevalence peaked in younger age groups, and blood eosinophil concentrations during A. ceylanicum infection were higher than those for N. americanus infection. Female sex was associated with a lower risk for either hookworm infection. Cure rates after 1 dose of albendazole were greater for A. ceylanicum (93.3%) than N. americanus (65.9%) hookworm (p<0.001). Lower N. americanus hookworm cure rates were unrelated to β-tubulin single-nucleotide polymorphisms at codons 200 or 167. A. ceylanicum hookworm infection might be more common in humans than previously recognized.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albendazole; Ancylostoma; Ancylostomiasis; Animals; Anthelmintics; Child; Child, Preschool; Feces; Female; Humans; Infant; Male; Middle Aged; Myanmar; Refugees; Thailand; Young Adult
PubMed: 30014834
DOI: 10.3201/eid2408.180280