What is Ascariasis and Trichuriasis?

Soil-transmitted helminths are a family of intestinal worms that include the organisms that cause ascariasis, hookworm (profiled separately), and trichuriasis. Ascariasis and trichuriasis are transmitted through ingestion of parasite eggs in contaminated soil. While ascariasis and trichuriasis are associated with a relatively small number of deaths, they can result in intestinal symptoms, weakness, and malnutrition which, over time, can impact childhood development and adult productivity.

Global Burden

Ascariasis and Trichuriasis

Ascariasis, also known as common roundworm, and trichuriasis, also known as whipworm, are found throughout the tropics and subtropics. It is estimated that more than 1 billion people are infected worldwide including 300 million suffering from severe morbidity.1

WHO Region DALY (in thousands)1
Ascariasis Trichuriasis
Africa 915 236
Americas 60 73
Eastern Mediterranean 162 61
South-East Asia 404 372
Western Pacific 308 269
Total: 1,849 1,011

The economic impact of ascariasis and trichuriasis is difficult to estimate. The World Health Organization (WHO) estimates that deworming may increase adult income by 40%.1

Causative Agent

example

Ascariasis is caused by the intestinal roundworm, Ascaris lumbricoides. Humans become infected by ingesting eggs from contaminated soil. The eggs release larvae in the small intestine which bore through the intestinal wall and circulate through the lymphatic system, ultimately reaching the lungs. Over a period of 2-3 months larvae mature through a process that involves coughing up and swallowing larvae from the lungs. Once swallowed, the worms return to the small intestine, were the adult female worm burrows through the mucosa and begins producing about 200,000 eggs per day. The eggs are shed into the feces allowing the infection to propagate. Most infections with ascariasis are asymptomatic, but moderate to heavy worm burdens can cause malabsorption of nutrients or obstruction of the intestine.

Trichuriasis, more commonly known as whipworm, is caused by the roundworm Trichuris trichiura. As with ascariasis, humans become infected by ingesting eggs from contaminated soil. The larvae of T. trichiura emerge in the small intestine and develop into adults in the large intestine where 3,000-7,000 eggs are shed into the feces per day. Although infection with a small number of worms is usually asymptomatic, heavier infections can cause diarrhea, cognitive impairment, anemia, and prolapsed rectum.

Pathogenesis

Female worms shed eggs into the stool of the host. When latrines or toilets are not available, eggs from the feces of infected hosts contaminate the soil and water. New hosts become infected upon ingestion of contaminated soil or water, often on unwashed food or from unwashed hands.

Current Control Strategy

Current control strategies for ascariasis and trichuriasis include a combination of mass drug administration (MDA) with benzimidazoles (albendazole or mebendazole) one to two times a year, based on prevalence levels in school-aged children, and improvement of sanitation to reduce fecal contamination in the local environment.

Existing Products

Drugs

Benzimidazoles (albendazole or mebendazole), pyrantel pamoate, and levamisole are all used to treat soil transmitted helminths, including ascariasis and trichuriasis. Treatment is challenging because of the way the worms are situated in the large intestine -- very little surface area is exposed to the drugs. Mass drug administration programs primarily consist of once-per-year single dose treatment with albendazole. Although this regimen is sufficient for the treatment of ascariasis, the impact on trichuriasis is less efficacious. In addition to the drugs recommended by the WHO (albendazole, mebendazole, levamisole, and pyrantel pamoate), new anthelmintic alternatives, such as tribendimidine and Nitazoxanide, have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials. Some new drugs for veterinary use, including monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand the drug spectrum for human treatments in the future.2

The goal for treating ascariasis and trichuriasis is not necessarily cure, but rather control by greatly reducing the number of worms and eggs present in a patient. As such, treatment response rates are dependent on the severity of a patient’s condition. While the cure rate indicates that room for improvement remains, most experts in the field primarily cite and evaluate egg reduction rates when assessing the success of a program or course of treatment.

Drug Response Rates Based on Meta Analysis2,3
 Treatment A. lumbricoides T. trichiura 
Cure Rate (%) Egg Reduction (%) Cure Rate (%) Egg Reduction (%)
Albendazole (1 day) 88 87-100 28 0-90
Albendazole (3 days) N/A N/A 53 81-100
Mebendazole (1 day) 95 96-100 36 81-93
Mebendazole (3 days) 92 91-100 63-80 38-99
Pyrantel pamoate (1 day) 88 88 31 52
Pyrantel pamoate (3 days) 92 99 27 77
Levamisole (1 day) 92 92-100 10 42

Albendazole is also used for MDA to treat lymphatic filariasis and other soil transmitted helminths, such as hookworm, providing crossover treatment for ascariasis and trichuriasis Ivermectin, which is also used to treat lymphatic filariasis, offers systematic effects for STH, especially for trichuriasis.

Tribendimidine was approved for the treatment of soil transmitted helminths in China in 2004. Despite positive efficacy data in animals and humans from China, the use of tribendimidine will likely remain limited until the drug is approved by the U.S. FDA or European regulatory agencies.3

Vaccines

There is currently no vaccine approved for the prevention of ascariasis or trichuriasis.

Diagnostics

Diagnosis of ascariasis and trichuriasis relies on microscopic examination of feces for egg contamination. This has an overall low sensitivity because of variable egg excretion. Furthermore, eggs of A. lumbricoides and T. trichuris are difficult to distinguish from the eggs of other worm infections.

References

  1. WHO (2010) First WHO report on neglected tropical diseases 2010: working to overcome the global impact of neglected tropical diseases.
  2. Hagel I, Giusti T. Ascaris lumbricoides: an overview of therapeutic targets. Infect Disord Drug Targets. 2010 Oct;10(5):349-67.
  3. Keiser J and Utzinger J (2010) “The drugs we have against major helminth infections.” Advances in Parasitology 73: 197-229.

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Drugs

Analysis

The development of novel drugs for ascariasis is not considered an immediate priority. New drugs for trichuriasis, which is less well controlled by single dose therapy with current drugs, may represent a greater need. Although drug resistance is possible, it has not yet been detected. A standard system to detect and respond to resistance is under development by the WHO. A proposed target product profile (TPP) for soil transmitted helminthes was recently published.1 At this point in time however, resources are focusing more heavily on improving the coverage of mass drug administration among school children rather than new product development.

Future drug discovery programs will most likely focus on new or optimized combination therapy programs, discovery of single products that can target multiple parasitic or neglected diseases in a single dose, or the repurposing of veterinary medications for worm infections, such as emodepside, monepantel, or derquantel. New drugs or combination therapeutics may be required if resistance is detected. Although repurposing of veterinary medications may represent the fastest path to new anti-helminth drugs, formal development of these drugs in humans is not currently active.1

Vaccines

Vaccines are not currently being developed for ascariasis or trichuriasis. However, these worms may share some homologous antigens with other helminths. More research is needed to understand the potential for cross protection against these worms through vaccines currently in development for the prevention of other helminth infections such as hookworm or schistosomiasis.

Diagnostics

New point-of-care diagnostics are needed for use in parallel with mass drug administration (MDA) programs. A key challenge of MDA is determining when mass treatment should stop. Diagnostics that can be used in extremely rural areas by minimally trained community volunteers (potentially those already involved in the MDA program) are needed to determine when transmission of hookworm has been interrupted in a village. The same diagnostics should be used to monitor communities to ensure reintroduction does not occur.

References

  1. Olliaro P et al. (2011) “Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases.” PLoS Neglected Tropical Diseases 5: e1138.

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The tools available for the development of drugs, vaccines, and diagnostics for ascariasis and trichuriasis are summarized below. Overall, the tools available to study these organisms are limited.

Drugs Development Tools

Basic Research: Target IdentificationTarget ValidationScreening: Hit/Lead Identification OptimizationPre-clinical ValidationClinical Validation

Genome: Ascaris lumbricoides EST library available

No sequencing or EST libraries available forTrichuris trichuria 

Key databases: http://www.nematode.net

In vitro culture: Eggs from adult Ascaris suum(pig model) can be isolated, hatched, and the larvae maintained in culture for about a month. Many people develop severe allergic reactions to handling adult worms making them difficult to work with in the laboratory.

Haemonchus contortus is also used as a model system.

Gene knock-outs: No

Conditional gene knock-outs: No

Transposon mutagenesis: No

RNAi: Yes

Other antisense technology: Yes

Viability assays: Possible with adult worms but not common

Transcription microarrays: Limited, primarily only forAscaris suum (pig model)

Proteomics: Limited, primarily only forAscaris suum (pig model)

Crystal structures: Limited

Whole-cell screening assays: No

Enzymatic screening assays: Limited

Animal models: Yes

Ascaris suum pig and mouse models

Trichuris muris mouse model

Trichuris suis pig model

Monitoring treatment efficacy: Yes

Availability of endpoints: Yes, clearance of eggs from stool

Availability of surrogate endpoints: No

Access to clinical trial patients/sites: Formal clinical trial sites not established, but patient populations may be identified through ongoing MDA programs.

Vaccines Development Tools

Basic Research: Antigen IdentificationImmune Response CharacterizationClinical Validation

See drug development tools above

Predictive animal models: Pig model more relevant, but more reagents are available for mouse model.

Detection of endogenous antigen specific response in clinical samples: Yes

Natural immunity well characterized: No, studies ongoing but complex. Primary focus of basic research is on allergens associated with ascaris worms.

Surrogate markers of protection: No 

Challenge studies possible: No

Diagnostics Development Tools

Basic Research: Biomarker IdentificationBiomarker ValidationClinical Validation

See drug development tools above

Biomarkers known: Yes

Access to clinical samples: Yes 

Possible sample types: Stool

Access to clinical trial patients/sites: Yes, if through MDA programs

Treatment available if diagnosed: Yes

References

Get Involved

To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs.