infection is the most common infectious cause of eosinophilic meningitis worldwide.1,2
To our knowledge, ours is the first epidemiologic study to use a systematic evaluation of laboratory data to identify and evaluate persons in an endemic area with eosinophilic meningitis that was likely caused by A. cantonensis
We found that, in our cohort of patients in Hawaii, headache and sensory symptoms may be prolonged and require long-term analgesia. Affected persons in Hawaii often did not report the classic exposure of snail or slug ingestion; it is possible that accidental ingestion of intermediate hosts (directly or through fresh produce) caused infection.
Our study shows that symptoms can be protracted. Previous reports suggest that headaches last up to 8 weeks,5,16
but we found that they may recur intermittently over 10 months.Paresthesia, hyperesthesia, and numbness also may persist for months.30,31
Sensory symptoms were notable for their migratory nature and the association between numbness and higher peripheral eosinophil counts. Vision changes (including blurred or double vision) were more frequently reported by case-patients in our cohort than in previous studies; these symptoms could be caused by larval invasion or an inflammatory response.13,15,16,18,32,33
Potential exposures within this cohort differ from exposures reported for point source outbreaks, particularly in Asia. With some exceptions, infected persons identified in outbreaks in Taiwan, Thailand, and elsewhere knowingly or intentionally consumed slugs or snails (e.g., during a meal or for medicinal purposes).14,15,18,27
In our study in Hawaii, only one person knowingly ate a snail (which was cooked and thus, unlikely to have caused infection), and three persons discovered a slug in their food/drink. Other studies have reported infection from consuming undetected small slugs, snails, or planaria on produce (e.g., in a Caesar salad and raw vegetable juice).5,10,11,28,34
Although we did not identify a point source for this outbreak, unintentional consumption of snails/slugs or larvae in homegrown produce likely occurred on the island of Hawaii; almost all case-patients there described consuming produce from their own (or a non-commercial) garden, usually unwashed. Environmental studies found A. cantonensis
larvae in slugs in the yards of the infant with a parasitologically confirmed case and two case-patients who shared a household.35,36
The possibility of transmission through snail/slug slime trails on produce requires further investigation. Studies have detected A. cantonensis
larvae and larval DNA in the slime trails of 12% of infected snails/slugs, but it is unclear whether the parasite can be transmitted in this mucus.9,37,38
Effective, practical strategies for removing A. cantonensis
larvae from potentially contaminated produce have not been identified. Although larvae can be killed by bleach, they may survive in vinegar and saturated cooking salt solutions.39
To our knowledge, detailed studies have not been done of larval removal after washing with water, but reports suggest cross-contamination of vegetables can occur in common wash buckets.40–43
Infection from consumption of unwashed, homegrown produce may have been compounded by changes in the snail/slug host populations around the time of the outbreak.23,36
In 2008, of 31 snail/slug species at selected nurseries in Hawaii, 29 (94%) species were alien to Hawaii, and 5 (16%) species had not previously been documented in the state.44
In particular, the introduction of Parmarion martensi
may have been a factor in the clustering of suspected angiostrongyliasis cases, especially on the island of Hawaii.23,36
This semi-slug was first documented on Oahu in 1996 and on the island of Hawaii in 2004.36,44
Data from a study in 2005 suggest that there were increasing numbers of P. martensi
in home gardens, particularly on the island of Hawaii;36
some of our case-patients reported similar anecdotal evidence. Juvenile forms of P. martensi
tend to be smaller than other slugs/snails and therefore, might be even less readily noticed on produce.36
Furthermore, they reportedly are efficient at transmitting A. cantonensis
, because a higher proportion are infected (compared with Veronicella cubensis
, the dominant large mollusk species in the area), they have greater parasite burdens, and they tend to enter human habitats (including houses and water tanks).36
Our understanding of transmission and the potential role of P. martensi is limited, in part because we were unable to identify a common source for this geographically and temporally dispersed cluster of suspected cases. Indeed, although we included a detailed food history, unrecognized exposures may have caused infection. Furthermore, the lack of a control group made it impossible to compare the frequencies of potential exposures and symptoms among case-patients with frequencies among uninfected persons; however, identification of an appropriate control group could be difficult, in part because of the possibility of asymptomatic or mild infection and the lack of a reliable serologic or diagnostic test.
Our study had other limitations. Only one case was confirmed parasitologically; the other 17 cases had compatible clinical and epidemiologic features.23
Misclassification of the cause of the patients' meningitis was possible, but in most angiostrongyliasis-endemic areas, parasitologic confirmation is unusual. Presumptive diagnosis is typical; recovery of larvae and adult worms from the CSF is rare, except among Taiwanese children.15
Although we sought to exclude all other known infectious and non-infectious etiologies of eosinophilic meningitis using data available in the medical records, we were unable to perform additional laboratory testing, because the study was retrospective. It is unlikely that a different, undiagnosed parasitic infection accounted for the cases of eosinophilic meningitis, because Hawaii is known to be hyperenzootic for A. cantonensis
but not for Gnathostoma spinigerum
or Baylisascaris procyonis
, the two other parasites commonly associated with eosinophilic meningitis.
Because of our case detection methods, we did not include persons who were asymptomatic, did not undergo an LP, or had CSF data that did not meet criteria for eosinophilic meningitis (e.g., fewer eosinophils might have been present if the LP was done early or late in the clinical course).5,16
Our case criteria might have biased our results by including more severe cases, but they increased the specificity of the case definition. As with all retrospective studies, physical examination data were limited by reliance on potentially incomplete medical records, and symptom and exposure recall bias was possible. Although we attempted to limit recall bias by including only the most recently diagnosed cases (see Materials and Methods), the fact that a median time of 4.5 months elapsed from symptom onset to the interview suggests that erroneous recall was possible.23
The persistence of symptoms at the time of the interview suggests that reporting was generally accurate but did impair our ability to determine the duration of some symptoms. Finally, asking about typical food consumption patterns is a common approach in investigations of prolonged outbreaks.
In conclusion, we described the clinical and laboratory features as well as possible exposures associated with suspected A. cantonensis infection in a cohort of persons in Hawaii from January 2003 to April 2005. We found that symptoms can be protracted; only a minority of patients reported complete recovery even months later. Clinicians should consider the diagnosis in persons with eosinophilic meningitis who live in (or have traveled to) Hawaii, even if a history of snail/slug ingestion is not elicited. Persons in endemic areas should be aware of the potential risk for infection through consumption of contaminated produce and may benefit from careful examination of raw food, especially leafy greens. Much remains unclear regarding the risk factors for transmission in Hawaii. Additional studies are needed to facilitate targeted public health interventions.