Guest Editor's Message: Eosinophilic Meningitis Caused by Angiostrongylus cantonensis, the Rat Lungworm: Biology, Distribution, Epidemiology, Detection, Diagnosis, Treatment, and Management

One of the major causes of eosinophilic meningitis is infection by the nematode Angiostrongylus cantonensis, the rat lung-worm. Angiostrongylus cantonensis was first described from southern China, but has now spread to many parts of the world as a result of the human-associated spread of both its definitive and intermediate hosts (rats and snails/slugs, respectively). The first cases in Hawai‘i were reported in 1961 but the disease has attracted increasing attention in Hawai‘i following outbreaks over the last decade.

The disease is contracted when people ingest the immature worms that are carried by snails and slugs. Ingestion is most often inadvertent - a small baby slug among lettuce leaves for instance. However, in some parts of the world raw snails are a delicacy and their ingestion can lead to disease, and there are cases, including one in Hawai‘i, in which people have deliberately eaten uncooked slugs, either on a dare when drunk, or for a bet.

The worms begin their development in rats, which pass them in their feces. The infected feces are eaten by snails and slugs in which the worms develop further. The snails and slugs are then eaten by rats, in which the worms develop further and reproduce, with this, the natural cycle, then repeating.

But if instead of rats, people eat the snails or slugs, the worms develop but die once they reach the central nervous system, particularly the brain. The physical damage to the nervous system and brain caused by the worms' movements, combined with the strong immune reaction caused by the dead worms that results in serious inflammation, can lead to symptoms including headache, stiff neck, numbness, tingling or pain in the skin, fever, nausea and vomiting, blurred vision, weakness, joint pain, and neurological abnormalities. More severe symptoms can include paralysis of the legs, bowel and bladder dysfunction, seizures, coma, and (rarely) death.

Angiostrongyliasis is mainly a tropical disease, but with the increasing spread of invasive species, including rats and molluscs, and global warming, which may increase the hosts' potential range, it has become an important emerging infectious disease. Stimulated by the increasing number of cases in Hawai‘i during the last decade, an international transdisciplinary scientific workshop on angiostrongyliasis was held August 16–18, 2011, in Honolulu,¹ expanding on a previous workshop in Bangkok in 2010.² The workshop convened scientists and clinicians from places as far apart as Brazil, China, Jamaica, Taiwan, Thailand, the mainland United States, and Hawai‘i, with expertise in a much broader range of fields than was represented at the Bangkok workshop, spanning ecology, parasitology, epidemiology, detection, diagnosis, treatment, and food safety. The workshop's goal was to develop a rigorous and concerted research agenda to address rat lungworm disease at a global scale through advancing an integrated understanding of all aspects of the disease. A prioritized list of objectives was developed¹ and the top needs in eight areas, as identified in this list, are presented in Table 1.

Table 1.

Identified Priorities for Research and Outreach: the Top Five Needs Identified in Each Focal Area (more than five if projects tied for fifth place).

Focus 1. Detection of Angiostrongylus cantonensis in hosts

Genomics / proteomics: sequence genome / develop proteomics for fast detection

Obtain comparative data on sensitivity and specificity of available techniques

Develop methods of parasite detection in fresh human food mainly vegetables and fruits

Sample other potential hosts, notably flatworms and freshwater crustaceans, to assess their potential as hosts and their parasite load

Develop ‘low tech’ detection methods

Gain a better understanding of the biology of the hosts as it relates to parasite transmission

Focus 2. Control of hosts in the field (rats, slugs/snails, paratenic hosts)

Identify paratenic hosts, their relevance and importance

Gain a better understanding of the basic biology of snails and slugs, including genetics, which could be useful in developing interventions

Undertake surveys of rats in areas where A. cantonensis has been reported (eg, south Florida, Rota)

Develop cultural methods of snail/slug control, such as natural barriers (eg, sand)

Gain a better understanding of the environmental variables that affect slug and snail host survival and reproduction, eg, humidity, temperature, etc, and the potential effects of climate change / global warming

Focus 3. Public education to minimize chance of infection

Involve children (ages 7–14) in educational efforts and build education about angiostrongyliasis into science/math (STEM) curriculum (in the United States there may be a National Science Foundation GK-12 grant opportunity)

Require continuing education for health care practitioners

Better define risk factors so that these can be the focus of education

Increase outreach to farmers and farmers' markets. Focus on potential impact on profits

Use social media networks, eg, Facebook, Twitter, etc., and contribute regularly

Define public health messages clearly and consistently

Create an angiostrongyliasis listserve

Focus 4. Control of hosts / larvae on produce (eg, washing / rinsing)

Evaluate different rinse ingredients

In the United States, obtain EPA and/or FDA approval of methods for washing produce, and similarly in Hawai‘i get approval from the Departments of Agriculture and Health, as well as other regulatory agencies

Undertake surveys to ascertain the distribution of larvae and hosts, including slugs/snails on different kinds of fresh produce

Develop a hand held LAMP (loop-mediated isothermal amplification) device or other simple methods for detection of A. cantonensis in the field

Investigate irradiation of produce as a sanitizing method

Focus 5. Diagnosis

Improve and standardize serology

Develop rapid tests for detection, eg, PCR, antigen detection, chromatography, ‘dipsticks’

Standardize clinical criteria for diagnosis

Validate PCR or other molecular methods for detection of A. cantonensis in patients

Develop a cooperative network for sharing specimens, antigens and DNA sequences

Focus 6. Treatment

Undertake well thought-out clinical trials

Assess the value of early use of anthelmintics

Standardize the protocol for lumbar puncture (LP), eg, are serial/repeat LPs beneficial; how often should they be done?

Develop guidelines for the use of steroid therapy, eg, when to start, dosage, rate of tapering off

Determine what should be the standard of care?

Focus 7. Pathophysiology

Determine the actual mechanism of neurological injury in humans: (i) increased intra-cranial pressure, (ii) the inflammatory reaction, and if so which cytokines are involved, (iii) mechanical damage from worm migration, or (iv) a combination of these

Develop the best animal model for human disease

Assess the influence of parasite inoculum on incubation period and severity of the illness, in particular how the number of parasites in the inoculum correlates with the number of parasites reaching the brain

Determine how the parasites invade the central nervous system (CNS)

Determine at which larval stage intervention (anthelmintics) will prevent symptoms

Investigate pathophysiology in infected hosts (slugs/snails, rat, paratenic hosts)

Investigate the mechanism by which steroid treatment alleviates symptoms: inflammation reduction or reduction of intra-cranial pressure

Focus 8. Epidemiology

Refine understanding of risk factors

Develop better tools for molecular epidemiology

Standardize the methodology of environmental assessments in terms of location characteristics and the geographical distribution of the parasite and the disease in a region

Develop centralized reporting of epidemiological findings

Determine the relationship between infection and disease: what triggers the disease, how the level of exposure is related to incidence of the disease

There is a need to raise awareness and understanding of angiostrongyliasis within the medical community as well as the general public. This special issue of the Hawai‘i Journal of Medicine and Public Health is part of this effort. The issue includes 24 articles. Of these, 23 represent or expand on presentations made at the workshop and range from describing the basic life-cycle of the parasite, the diversity of molluscan hosts, and detection of the parasite, to diagnosis and treatment of the disease. An additional article that was not part of the workshop describes research that addresses important food safety aspects of prevention of infection and adds an additional dimension to the diversity of the workshop-derived articles. Most of the articles (18) are full papers, four are extended versions of the original abstracts of the workshop presentations, and two are the original workshop abstracts. All the full papers were reviewed by at least two reviewers; abstracts were reviewed by the guest editor. The articles represent work undertaken in all the major regions of the world in which angiostrongyliasis is emergent.

This is the first time that such a comprehensive diversity of articles on angiostrongyliasis has been brought together in a single publication. As such, it is hoped that it will provide an informative overview of the disease as well as an entry to the rapidly increasing body of literature dealing with all aspects of it.

The workshop website (http://www.hawaii.edu/cowielab/Angio%20website%20home.htm) provides access to all the workshop presentations, although some were modified so that as yet unpublished data are not available. A summary of the workshop has been published in the on-line version of the journal Emerging Infectious Diseases.¹

Conflict of Interest

The author identifies no conflict of interest.