Sci Simple

New Science Research Articles Everyday

# Biology # Molecular Biology

The Impact of Toxocara canis on Health

Learn about Toxocara canis, its effects on dogs and humans, and drug resistance.

Theresa A. Quintana, Matthew T. Brewer, Jeba R. Jesudoss Chelladurai

― 6 min read


Toxocara canis: A Hidden Toxocara canis: A Hidden Threat humans alike. Toxocara canis poses risks to dogs and
Table of Contents

Toxocara canis is a type of roundworm that primarily infests dogs. It is part of a group of parasites that can also affect humans, leading to a condition called toxocariasis. This is not just a problem for our furry friends, as millions of people, especially those in low-income areas, may also be exposed to this worm. In the United States, the infection rate is estimated to be around 5% to 20% of the population, translating to roughly 17 to 66 million people. Globally, around 1.52 billion people might be exposed to Toxocara species. The risk of infection is even higher in developing countries where sanitation is poor and contact with animals is common.

How Do Humans Get Infected?

People typically become infected with Toxocara canis by accidentally swallowing larvated eggs. These tiny eggs can be found in contaminated soil or on the fur of infected animals. After ingestion, the eggs hatch in the intestines, and the larvae can migrate throughout the body, causing various symptoms. Some people may experience mild issues like fever or abdominal pain, while others can suffer from more serious conditions involving their organs or eyes.

Life Cycle of Toxocara canis

The life cycle of T. canis starts when adult worms live in the small intestine of infected dogs. Dogs usually get infected by eating larvated eggs found in dirt or on other animals. Once ingested, these eggs hatch in the intestines and the larvae make their way to the liver and lungs. In young dogs, the larvae are coughed up from the lungs, swallowed, and then mature into adult worms in the intestines. The adult females produce thousands of eggs that are expelled in the dog’s feces, contaminating the environment. These eggs can survive for long periods, heightening the risk of human exposure.

Impact on Dogs

The effects of T. canis infection in dogs can vary based on the severity of the infection and the age of the dog. In severe cases, dogs may face weight loss, poor growth, vomiting, and diarrhea. Fortunately, various medications can successfully treat these infections in dogs, including a few different classes of drugs. However, in older dogs, the larvae can become dormant in tissues, which means the infection can remain a threat even if the adult worms are treated.

The Mystery of Drug Resistance

One of the puzzling aspects of T. canis is how certain larvae can resist treatments. While drugs like ivermectin and moxidectin work well against adult worms, the dormant larvae in tissues seem to tolerate these treatments. The exact reasons behind this tolerance are not fully understood yet.

Other Factors in Drug Resistance

The challenge of drug resistance is not limited to T. canis. Many parasitic worms may have other protective mechanisms, such as specific proteins that help pump drugs out of their cells. These proteins, known as P-glycoproteins, are involved in drug transport and can play a major role in resistance.

Understanding the Worm's Genes

To understand how T. canis responds to medications, scientists need to take a closer look at its genes. So far, there hasn't been much information about the full set of genes in T. canis, but research has started to explore how this worm's genes behave when exposed to drugs.

Research Purpose

In recent studies, scientists aimed to analyze the gene activity in T. canis larvae after exposure to treatments like ivermectin and moxidectin. They looked specifically at how these drugs influence the expression of genes thought to be involved in drug resistance.

The Experiment

For the experiments, researchers collected T. canis from a naturally infected dog. They let the eggs hatch into larvae in a controlled environment. The larvae were then exposed to either the drugs or left untreated. Afterward, the researchers analyzed the genes expressed in the larvae.

What Were the Findings?

The results revealed that many genes were significantly affected by the drug treatments. In total, scientists identified several hundred genes that reacted differently when exposed to ivermectin or moxidectin compared to untreated larvae.

Upregulated Genes

In the experiments, some genes showed increased activity in response to the drugs. These genes are important as they may contribute to how the worm manages to survive even when exposed to treatments that generally kill it.

Downregulated Genes

Conversely, other genes showed decreased activity when larvae were treated with these drugs, suggesting that the treatment alters the worms' normal functioning.

The Role of GluCls

One key component of the drugs' effectiveness is their ability to target certain channels in the worms' nerves called glutamate-gated chloride channels (GluCls). In our experiments, it was found that the expression of some GluCls decreased in the presence of ivermectin, which might suggest a potential mechanism for drug resistance.

P-glycoprotein Genes

In addition to GluCls, the worms also express various P-glycoprotein genes. Some of these genes were shown to have altered activity in response to drug exposure. This suggests they might be involved in the worms’ ability to resist treatment.

Genetic Analysis

To analyze the genetic makeup of T. canis, researchers employed advanced sequencing techniques. They focused on understanding how many genes were active under different conditions.

The Results of Genetic Analysis

The genetic analysis revealed thousands of sequences, with many genes responding differently based on whether larvae were exposed to drugs or left untreated.

Energy Metabolism and Other Functions

Exposure to drugs appeared to affect the metabolism of the larvae. The researchers noted that some genes involved in generating energy were upregulated, suggesting that the worms might be trying to counter the effects of the drugs.

Neuronal Activity

Furthermore, genes related to neuronal structure and function also showed changes in expression. Some increased while others decreased, indicating that the drugs might disrupt the normal nervous system activities of the worms.

Impacts on Reproduction

The research also hinted that the treatments could interfere with reproductive processes in T. canis. Certain genes involved in reproduction were downregulated, raising concerns about how these drugs could impact the worms' ability to reproduce.

Conclusion: A Call for Continued Research

In the end, while the research shed light on how T. canis responds to treatments, it also highlighted the complexities of drug resistance. Further studies are needed to understand the exact mechanisms behind this resistance and to develop more effective treatments.

Final Thought

Toxocara canis may be a small roundworm, but it proves that even the tiniest creatures can have significant impacts on health! So, let’s keep our furry friends and ourselves safe by maintaining proper hygiene and regular vet visits. Remember, a worm-free dog is a happy dog!

Original Source

Title: Transcriptional responses to in vitro macrocyclic lactone exposure in Toxocara canis larvae using RNA-seq

Abstract: Toxocara canis, the causative agent of zoonotic toxocariasis in humans, is a parasitic roundworm of canids with a complex lifecycle. While macrocyclic lactones (MLs) are successful at treating adult T. canis infections when used at FDA-approved doses in dogs, they fail to kill somatic third-stage larvae. In this study, we profiled the transcriptome of third-stage larvae derived from larvated eggs and treated in vitro with 10 {micro}M of the MLs - ivermectin and moxidectin with Illumina sequencing. We analyzed transcriptional changes in comparison with untreated control larvae. In ivermectin-treated larvae, we identified 608 differentially expressed genes (DEGs), of which 453 were upregulated and 155 were downregulated. In moxidectin-treated larvae, we identified 1,413 DEGs, of which 902 were upregulated and 511 were downregulated. Notably, many DEGs were involved in critical biological processes and pathways including transcriptional regulation, energy metabolism, neuronal structure and function, physiological processes such as reproduction, excretory/secretory molecule production, host-parasite response mechanisms, and parasite elimination. We also assessed the expression of known ML targets and transporters, including glutamate-gated chloride channels (GluCls), and ATP-binding cassette (ABC) transporters, subfamily B, with a particular focus on P-glycoproteins (P-gps). We present gene names for previously uncharacterized T. canis GluCl genes using phylogenetic analysis of nematode orthologs to provide uniform gene nomenclature. Our study revealed that the expression of Tca-glc-3 and six ABCB genes, particularly four P-gps, were significantly altered in response to ML treatment. Compared to controls, Tca-glc-3, Tca-Pgp-11.2, and Tca-Pgp-13.2 were downregulated in ivermectin-treated larvae, while Tca-abcb1, Tca-abcb7, Tca-Pgp-11.2, and Tca-Pgp-13.2 were downregulated in moxidectin-treated larvae. Conversely, Tca-abcb9.1 and Tca-Pgp-11.3 were upregulated in moxidectin-treated larvae. These findings suggest that MLs broadly impact transcriptional regulation in T. canis larvae.

Authors: Theresa A. Quintana, Matthew T. Brewer, Jeba R. Jesudoss Chelladurai

Last Update: 2024-12-20 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.20.629602

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.20.629602.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

Similar Articles