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Parasitology Apr 2021The soil-transmitted helminth Ascaris lumbricoides infects ~800 million people worldwide. Some people are heavily infected, harbouring many worms, whereas others are...
The soil-transmitted helminth Ascaris lumbricoides infects ~800 million people worldwide. Some people are heavily infected, harbouring many worms, whereas others are only lightly infected. The mechanisms behind this difference are unknown. We used a mouse model of hepatic resistance to Ascaris, with C57BL/6J mice as a model for heavy infection and CBA/Ca mice as a model for light infection. The mice were infected with the porcine ascarid, Ascaris suum or the human ascarid, A. lumbricoides and immune cells in their livers and spleens were enumerated using flow cytometry. Compared to uninfected C57BL/6J mice, uninfected CBA/Ca mice had higher splenic CD4+ and γδ T cell counts and lower hepatic eosinophil, Kupffer cell and B cell counts. Infection with A. suum led to expansions of eosinophils, Kupffer cells, monocytes and dendritic cells in the livers of both mouse strains and depletions of hepatic natural killer (NK) cells in CBA/Ca mice only. Infection with A. lumbricoides led to expansions of hepatic eosinophils, monocytes and dendritic cells and depletions of CD8+, αβ, NK and NK T cells in CBA/Ca mice, but not in C57BL/6J mice where only monocytes expanded. Thus, susceptibility and resistance to Ascaris infection are governed, in part, by the hepatic immune system.
Topics: Animals; Ascariasis; Ascaris lumbricoides; Ascaris suum; Disease Resistance; Disease Susceptibility; Flow Cytometry; Immunity, Innate; Liver; Male; Mice; Mice, Inbred C57BL; Spleen
PubMed: 33431071
DOI: 10.1017/S0031182021000020 -
Frontiers in Immunology 2023The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including...
INTRODUCTION
The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions.
METHODS
The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression.
RESULTS AND DISCUSSION
The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.
Topics: Humans; Animals; Ascaris lumbricoides; Benin; COVID-19; Diabetes Mellitus, Type 2; Pandemics; SARS-CoV-2; Ascaris; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37622109
DOI: 10.3389/fimmu.2023.1233082 -
Frontiers in Pediatrics 2022The identification of gene-environment interactions allows the recognition of groups with higher risk of morbidity. This study evaluated the interaction between the...
INTRODUCTION
The identification of gene-environment interactions allows the recognition of groups with higher risk of morbidity. This study evaluated the interaction between the presence of TLR4 gene polymorphisms and infection with severe bronchiolitis in a tropical Colombian region.
METHODS
We included all infants younger than 24 months hospitalized due to bronchiolitis in Hospital centers in the county of Rionegro, Colombia. To identify interaction between severe bronchiolitis and presence of TLR4 polymorphisms and infection, we used log-binomial regression.
RESULTS
Four hundred and seventeen infants were hospitalized due to bronchiolitis, of which 115 (27%) had severe bronchiolitis. In infants with respiratory syncytial virus (RSV) acute infection and positive anti-Ascaris IgE, TLR4 Asp299Gly was associated to low risk of severe bronchiolitis (OR 0.09, CI 95% 0.01-0.48). Conversely, in infants RSV negative with negative anti-Ascaris IgE, TLR4 Asp299Gly was associated with an increased risk of severe bronchiolitis (OR 14.5, CI 95% 2.2-96).
CONCLUSION
In our population there is an interaction between the presence of severe bronchiolitis, TLR4 Asp299Gly and Ile399Thr polymorphisms, anti-Ascaris IgE levels and RSV. This association should be evaluated in other populations to elucidate its role in the pathogenesis of severe bronchiolitis.
PubMed: 35573947
DOI: 10.3389/fped.2022.876882 -
Current Biology : CB Sep 2020Germline and somatic genomes are in general the same in a multicellular organism. However, programmed DNA elimination leads to a reduced somatic genome compared to...
Germline and somatic genomes are in general the same in a multicellular organism. However, programmed DNA elimination leads to a reduced somatic genome compared to germline cells. Previous work on the parasitic nematode Ascaris demonstrated that programmed DNA elimination encompasses high-fidelity chromosomal breaks and loss of specific genome sequences including a major tandem repeat of 120 bp and ~1,000 germline-expressed genes. However, the precise chromosomal locations of these repeats, breaks regions, and eliminated genes remained unknown. We used PacBio long-read sequencing and chromosome conformation capture (Hi-C) to obtain fully assembled chromosomes of Ascaris germline and somatic genomes, enabling a complete chromosomal view of DNA elimination. We found that all 24 germline chromosomes undergo comprehensive chromosome end remodeling with DNA breaks in their subtelomeric regions and loss of distal sequences including the telomeres at both chromosome ends. All new Ascaris somatic chromosome ends are recapped by de novo telomere healing. We provide an ultrastructural analysis of Ascaris DNA elimination and show that eliminated DNA is incorporated into double membrane-bound structures, similar to micronuclei, during telophase of a DNA elimination mitosis. These micronuclei undergo dynamic changes including loss of active histone marks and localize to the cytoplasm following daughter nuclei formation and cytokinesis where they form autophagosomes. Comparative analysis of nematode chromosomes suggests that chromosome fusions occurred, forming Ascaris sex chromosomes that become independent chromosomes following DNA elimination breaks in somatic cells. These studies provide the first chromosomal view and define novel features and functions of metazoan programmed DNA elimination.
Topics: Animals; Ascaris suum; Chromosome Mapping; DNA, Helminth; Female; Genome, Helminth; Helminth Proteins; Male; Repetitive Sequences, Nucleic Acid; Sex Chromosomes; Telomere
PubMed: 32679104
DOI: 10.1016/j.cub.2020.06.058 -
PLoS Neglected Tropical Diseases Sep 2021The treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently...
BACKGROUND
The treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently high. This high drug pressure may result in the development of BZ resistance in STHs and so there is an urgent need for surveillance systems detecting molecular markers associated with BZ resistance. A critical prerequisite to develop such systems is an understanding of the gene family encoding β-tubulin proteins, the principal targets of BZ drugs.
METHODOLOGY AND PRINCIPAL FINDINGS
First, the β-tubulin gene families of Ascaris lumbricoides and Ascaris suum were characterized through the analysis of published genomes. Second, RNA-seq and RT-PCR analyses on cDNA were applied to determine the transcription profiles of the different gene family members. The results revealed that Ascaris species have at least seven different β-tubulin genes of which two are highly expressed during the entire lifecycle. Third, deep amplicon sequencing was performed on these two genes in more than 200 adult A. lumbricoides (Ethiopia and Tanzania) and A. suum (Belgium) worms, to investigate the intra- and inter-species genetic diversity and the presence of single nucleotide polymorphisms (SNPs) that are associated with BZ resistance in other helminth species; F167Y (TTC>TAC or TTT>TAT), E198A (GAA>GCA or GAG>GCG), E198L (GAA>TTA) and F200Y (TTC>TAC or TTT>TAT). These particular SNPs were absent in the two investigated genes in all three Ascaris populations.
SIGNIFICANCE
This study demonstrated the presence of at least seven β-tubulin genes in Ascaris worms. A new nomenclature was proposed and prioritization of genes for future BZ resistance research was discussed. This is the first comprehensive description of the β-tubulin gene family in Ascaris and provides a framework to investigate the prevalence and potential role of β-tubulin sequence polymorphisms in BZ resistance in a more systematic manner than previously possible.
Topics: Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Ascaris suum; Benzimidazoles; Drug Resistance; Humans; Tubulin
PubMed: 34570778
DOI: 10.1371/journal.pntd.0009777 -
Cureus Dec 2022is the most common type of helminth infection in humans. It affects more than one billion of the world's population. Children living in developing nations are prone to... (Review)
Review
is the most common type of helminth infection in humans. It affects more than one billion of the world's population. Children living in developing nations are prone to ascariasis, presenting with obstructive biliary illnesses. Migration of worms through the major duodenal papilla to the hepatobiliary system leads to symptoms of biliary colic and complications along the biliary tree. In April 2022, we performed a systematic review of case reports to identify and examine cases of gallbladder ascariasis worldwide. A methodical search using PubMed, Semantic Scholar, ScienceDirect, and Directory of Open Access Journals yielded 2773 studies. After duplicate removal, title, abstract, and content screening, retrieval, and quality assessment, 13 studies met the criteria for this systematic review of case reports. The cases and results from these 13 studies revealed gallbladder ascariasis in different age groups worldwide. This systematic review discusses ascariasis, explicitly highlighting its presence in the gallbladder, symptomatic presentation, laboratory/imaging findings, complications, and approach to management.
PubMed: 36654632
DOI: 10.7759/cureus.32545 -
Parasitology Dec 2021Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to...
Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to control and eradicate ascariasis in endemic regions have been met with significant challenges including high-rates of re-infection and potential development of anthelminthic drug resistance. Vaccines against ascariasis are a key tool that could break the transmission cycle and lead to disease eradication globally. Evolution of the vaccine pipeline has progressed, however no vaccine product has been brought to human clinical trials to date. Advancement in recombinant protein technology may provide the first step in generating an vaccine as well as a pan-helminthic vaccine ready for human trials. However, several roadblocks remain and investment in new technologies will be important to develop a successful human vaccine that is critically needed to prevent significant morbidity in -endemic regions around the world.
Topics: Animals; Ascariasis; Ascaris; Humans; Vaccine Development; Vaccines
PubMed: 35586777
DOI: 10.1017/s0031182021001347 -
PloS One 2022In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic...
In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.
Topics: Adolescent; Albendazole; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Cross-Sectional Studies; Feces; Helminthiasis; Hookworm Infections; Humans; Longitudinal Studies; Soil; Trichuriasis; Trichuris
PubMed: 35960935
DOI: 10.1371/journal.pone.0272821 -
Current Opinion in Microbiology Aug 2016Maintenance of genome integrity is essential. However, programmed DNA elimination removes specific DNA sequences from the genome during development. DNA elimination... (Review)
Review
Maintenance of genome integrity is essential. However, programmed DNA elimination removes specific DNA sequences from the genome during development. DNA elimination occurs in unicellular ciliates and diverse metazoa ranging from nematodes to vertebrates. Two distinct groups of nematodes use DNA elimination to silence germline-expressed genes in the soma (ascarids) or for sex determination (Strongyloides spp.). Data suggest that DNA elimination likely evolved independently in these nematodes. Recent studies indicate that differential CENP-A deposition within chromosomes defines which sequences are retained and lost during Ascaris DNA elimination. Additional studies are needed to determine the distribution, functions, and mechanisms of DNA elimination in nematodes.
Topics: Animals; Ascaris; Base Sequence; Centromere Protein A; DNA, Protozoan; Female; Gene Silencing; Male; Sequence Deletion; Sex Determination Processes; Strongyloides
PubMed: 27315434
DOI: 10.1016/j.mib.2016.05.012 -
α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG.The Journal of Allergy and Clinical... Apr 2021IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate... (Comparative Study)
Comparative Study
BACKGROUND
IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated.
OBJECTIVE
We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya.
METHODS
IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children.
RESULTS
In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG were not high in Ecuador, but were greater than in children from the United States.
CONCLUSIONS
These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.
Topics: Adolescent; Adult; Animals; Ascaris; Child; Child, Preschool; Diet; Disaccharides; Ecuador; Feces; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Immunoglobulin G; Kenya; Male; Prevalence; Red Meat; Trichuris; Virginia; Young Adult
PubMed: 33539899
DOI: 10.1016/j.jaci.2020.12.650