The hookworm larval antigen (ASP-3) was identified as a protective antigen linked to recent larval vaccines. Additionally, there is a positive correlation between human anti-ASP-2 antibodies and the reduction of heavy-intensity hookworm infection in populations endemic to hookworm. Data has confirmed that recombinant ASP-2 can partially protect animals against larval hookworm infections. 

Vaccine Construction

Pre-clinical testing and manufacture of Na-ASP-2 from N. americanus were finalized in 2004. Clinical testing was expected to take place in 2005 following approval from the FDA. This vaccine will be developed in the nonprofit sector and distribution will be targeted to populations of susceptible individuals in moderately and/or heavily impacted regions. 

Vaccine Development Process

Immunization would affect the transmission of hookworm larvae and not adult parasites living within the gastrointestinal tract of infected individuals. Therefore, the first dose would need to be administered after deworming. Vaccination administration would rely on established infrastructure, such as school wide deworming programs. Given that hookworm infections impact impoverished populations, there is a small commercial market available. Investment for manufacturing and industrial scale-up is still necessary to provide the vaccine to marginalized communities. 

Distribution of the Vaccine

Hookworm vaccines will primarily affect the larval stage of the parasitic worm by inducing the production of IgG antibodies. These antibodies will prevent larval development, reducing the population of larvae that develop into adult worms. This will lower mortality rates by preventing the adult hookworms from entering the host’s gastrointestinal tract and producing intestinal blood loss. 

Function of Hookworm Vaccines

The Human Hookworm Vaccine Initiative (HHVI) is in the process of developing a functional and safe vaccine. HHVI is a non-profit collaboration at the George Washington University, London School of Hygiene and Tropical Medicine and the Oswaldo Cruz Foundation (vaccine development has been sponsored by the Sabin Vaccine Institute). Hookworm vaccine development involves research, process development, vaccine manufacturing and control and pre-clinical/clinical testing. 

Tulane University

- Etiology	
- Global distribution
- Clinical features
- Epidemiology 
- Progression of Hookworm infection
- Global disease burden
- Hookworm control strategies
- Na-ASP-2 Hookworm Vaccine

Hookworm

Hookworms are parasitic worms that infect the small intestine, with the highest prevalence in sub-Saharan Africa and eastern Asia. 

Hookworm: “The Great Infection of Mankind”
Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P (2005) Hookworm: “The Great Infection of Mankind”. PLOS Medicine 2(3): e67. https://doi.org/10.1371/journal.pmed.0020067

Hookworm: "The Great Infection of Mankind"

Adult hookworms may destroy the host through intestinal hemorrhage. These parasites ingest the blood rupturing erythrocytes and degrading hemoglobin in the process. Hookworm infections cause the disease silent blood loss, which leads to anemia and malnutrition. Generally, there is a positive correlation between parasite population and destruction of RBCs in the host (women of reproductive age, children and other populations with low iron). In children, chronic infections may lead to growth retardation and cognitive impairments. Infections in pregnant women may lead to negative maternal-fetal outcomes. 

Progression of Hookworm Infection

Current control strategies target the reduction of morbidity rates through mass treatments (deworming) of populations afflicted with the parasite. These mass drug campaigns include the distribution of anthelmintic drugs, benzimidazoles (BZAs), levamisole and pyrantel. Continued investment in deworming should be complemented by sanitation and access to safe drinking water. The World Health Organization has led campaigns to distribute doses of these drugs to schools with the highest rates of STH infections. The deworming of students has many health benefits including: 
- Improved iron and hemoglobin levels
- Physical growth and fitness
- Cognition

There are also a number of societal benefits including 
- Advancements in education
- Reduced community transmission of ascaris and trichuris infections


Hookworm Control Strategies

Na-ASP-2 Hookworm Vaccine

Hookworm infection is caused by the nematode parasites Necator americanus and organisms within the genus Ancylostoma. Soil-transmitted helminths (STHs) include:

- N. americanus (primary organism that causes hookworm infection)
- A. duodenale
- Roundworm
- Ascaris lumbricoides
- Trichuris trichiura 


Etiology of Hookworm

Despite a lack of surveillance mechanisms, extensive review of literature places the number of global cases as approximately 740 million people since 1990. The highest prevalence occurs in sub-Saharan Africa and eastern Asia. Higher transmission rates are correlated with impoverished areas in southern China, the Indian subcontinent and the Americas. The neglected status of hookworm is associated with high hookworm prevalence rates among the world’s poorest populations. 

Global Distribution of Hookworm

This parasitic infection results from the exposure of infective larval stages through the skin. Following entry of the pathogen, the larvae travel through the body to the lungs before ending in the gastrointestinal tract. The worms reproduce to form more than 30,000 eggs per day, which exit the host through the expulsion of feces. 

Clinical Features of Hookworm

Hookworm morbidity is proportional to the number of adult parasites inhabiting the patient. The severity of infection is determined through quantitative fecal egg counts and ranges from modern infections to heavily intense infections. 
- Moderate-intensity infections: 2,000-3,999 eggs per gram of feces
- Heavy-intensity infections: 4,000 or more eggs per gram of feces

Unlike other STH infections, hookworm infections portray an age-intensity profile where the severity of disease rises with age or plateaus in adulthood. Although this is largely observed in patients, the biological basis for this phenomenon is unknown. 


Epidemiology of Hookworm

The global disease burden, as analyzed through disability-adjusted life years, overwhelmingly exceeds other tropical diseases other than malaria, leishmaniasis and lymphatic filariasis. Hookworm infections are correlated with increased school absences and, as a result, a decreased future socioeconomic productivity. This research reflects that hookworm, similar to other NTDs, promotes long-term disability and increases the likelihood that a marginalized population will remain in impoverished conditions. 

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