Cluster of 19 Cases of Eosinophilic Meningitis due to Angiostrongylus cantonensis in Lifou, New Caledonia: An Outbreak Investigation

Cluster of 19 Cases of Eosinophilic Meningitis due to Angiostrongylus cantonensis in Lifou, New Caledonia: An Outbreak Investigation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cluster of 19 Cases of Eosinophilic Meningitis due to Angiostrongylus cantonensis in Lifou, New Caledonia: An Outbreak Investigation DUCROT Yves-Marie, Jean-Sebastien MORA, Morgane BAHU, Alexandre BOURLES, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9272013/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Eosinophilic meningitis due to Angiostrongylus cantonensis is an emerging parasitic disease worldwide, while remaining endemic in the Pacific region for several decades. In New Caledonia, a small number of sporadic cases occur each year, and the route of transmission is often unclear. In January 2023, an unusual cluster of three cases occurred in a small village following community festivities, leading to an epidemiological investigation. Methods We conducted a retrospective epidemiological and environmental investigation approximately one month after the suspected exposure. Cases were defined according to international criteria and classified as confirmed, probable, or suspected. Clinical data were collected from medical records and interviews. Food exposures were reconstructed using participant interviews. Environmental observations focused on potential contamination sources in food preparation areas. Serological analyses were performed in symptomatic and asymptomatic exposed individuals. Results Nineteen cases were identified, including three confirmed and sixteen suspected cases. Among suspected cases, seven were classified as high suspicion, eight as moderate, and one as low suspicion. The most common symptom was headache (n = 16), frequently associated with vomiting (n = 9) or paresthesias (n = 4). All cases attended festivities on December 27–28, suggesting a common exposure period. The median incubation time was 3 weeks (IQR: 2–4). Two main exposure hypotheses were identified: beverages diluted with rainwater and contamination of blended fruit juice prepared in an open-air kitchen. Environmental observations revealed rats and gastropods near food preparation areas, including on utensils left to dry outdoors. No parasite DNA was detected in water samples. Serological testing performed nine months later in ten exposed asymptomatic individuals was positive in all cases. Conclusions This investigation considers the possibility of waterborne transmission of A. cantonensis , although the most plausible hypothesis is the accidental incorporation of a heavily infected gastropod into blended fruit juice during preparation, potentially facilitated by open-air kitchens in rural Pacific settings. It highlights the diagnostic and epidemiological challenges of this infection in endemic areas, where milder or nonspecific presentations may not lead to lumbar puncture. Serological testing may assist in case identification but remains limited by cross-reactivity and prior exposure. Eosinophilic meningitis New Caledonia Angiostrongylus cantonensis Platydemus manokwari angiostrongyliasis outbreak investigation emerging infectious disease Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Angiostrongylus cantonensis (AC), the rat lungworm can accidentally infect humans, leading to a clinical syndrome known as eosinophilic meningitis (EM). After an incubation period typically ranging from 6 to 35 day [ 1 ], the disease most often presents with persistent headaches, erratic pain in the spine and limbs, and occasionally motor or sensory deficits or mild meningeal signs. Cerebrospinal fluid (CSF) analysis typically reveals eosinophilic pleocytosis. These manifestations result from the migration of larvae in the central nervous system, where they eventually die. In cases of severe infection, the associated inflammatory reaction may lead to neurological sequelae, impaired consciousness, or even death [ 1 ]. Current treatment recommendations favor early administration of corticosteroids combined with albendazole for approximately two weeks [ 2 ]. The life cycle of Angiostrongylus cantonensis involves mollusks as intermediate hosts, which become infected by ingesting rat feces containing first-stage larvae. Within the mollusk tissues, larvae develop into infective third-stage larvae. The cycle is completed when rats consume infected mollusks. Larvae may also be transferred to other animals such as planarians, lizards, or crustaceans, which act as paratenic hosts [ 3 ]. Human infection is usually associated with the intentional or accidental consumption of raw or undercooked mollusks or paratenic hosts. However, contamination of fresh produce or beverages through contact with infected mollusks has also been suggested [ 4 ]. Eosinophilic meningitis due to A. cantonensis is considered an emerging disease originally described in Southeast Asia. Since the 1940s, it has progressively spread throughout the Pacific region, likely due to the dispersal of infected rats transported on commercial and military ships [ 5 ]. The parasite is now reported in several regions worldwide, including Europe [ 6 – 8 ]. New Caledonia is a French overseas territory of approximately 280,000 inhabitants located between Australia and Fiji. It was among the first Pacific territories affected during this geographic expansion [ 9 , 10 ]. Currently, around ten sporadic cases are diagnosed annually, mainly among Melanesian populations living in rural areas and typically during the end of the cool and dry season [ 11 ]. The exact mode of contamination is rarely identified. In 1976, Ash suggested that terrestrial flatworms might play a role in transmission during the harvesting season of raw vegetables, possibly explaining the marked seasonality observed in New Caledonia [ 12 ]. In January 2023, three inhabitants of a small village in New Caledonia were hospitalized for neuroangiostrongyliasis. All of which had participated in several days of community festivities during the Christmas period. Other attendees also reported symptoms compatible with the infection. An epidemiological investigation of this cluster was therefore initiated [ 13 ]. POPULATION AND METHODS Setting The investigated village is located on Lifou Island, part of the Loyalty Islands in New Caledonia. Lifou is the largest island of the Loyalty Islands Province and lies approximately 190 km east of the main island of New Caledonia. The village has approximately 80 inhabitants. Lifou Island has a population of about 9,800 people, predominantly Melanesian, whose lifestyle still preserves important traditional elements organized around customary practices, yam cultivation, and religion. Housing mainly consists of wooden or corrugated metal constructions, with separate buildings for kitchens, sanitary facilities, and traditional thatched huts. Most households have access to electricity and running water. The region has a tropical maritime climate characterized by a hot and rainy season from November to April and a cooler and drier season from May to October. Two primary healthcare centers are located on the island; however, in case of medical or surgical emergencies, patients are transferred to the territorial hospital located in Nouméa. Epidemiological and environmental investigation The investigation began approximately one month after the suspected exposure period and was therefore largely retrospective, relying on medical records and participant interviews. The main difficulty was that the festivities had taken place over an entire week, with meals and activities organized both morning and evening. Case identification For the three hospitalized and confirmed cases, detailed hospital records were retrieved. Electronic medical records of residents who had consulted at the nearest health center between one and six weeks after the end of the festivities were systematically reviewed to identify symptoms compatible with neuroangiostrongyliasis. In addition, an investigator visited the village for several days to interview the majority of participants and identify potential cases who had not sought medical care (Fig. 1 ). Case definition Case definitions were based on the criteria proposed by the International Angiostrongylus and Angiostrongyliasis Alliance [ 14 ]. A confirmed case was defined as the presence of compatible symptoms together with a positive PCR for Angiostrongylus cantonensis in cerebrospinal fluid (CSF). A probable case was defined as compatible symptoms associated with eosinophilic meningitis and at least two minor criteria (compatible exposure, positive serology, or peripheral blood eosinophilia). A suspected case was defined as compatible symptoms together with at least one minor criterion. The minor exposure criterion corresponded to participation in meals during the festivities. Because this exposure criterion alone could classify a symptomatic individual as a suspected case, we further stratified suspected cases according to the presence of additional minor criteria, namely peripheral eosinophilia (> 500/mm³) and/or positive serology. Suspected cases were therefore categorized as follows: • low suspicion: 1 of 3 criteria • moderate suspicion: 2 of 3 criteria • high suspicion: 3 of 3 criteria This additional stratification was introduced for descriptive purposes and to better reflect the level of diagnostic probability among suspected cases. Clinical and epidemiological analysis A weekly epidemic curve was constructed based on the reported dates of symptom onset and the presumed date of exposure. Because the exact dates of symptom onset were sometimes uncertain, the week was used as the unit of time. The frequency of clinical manifestations was analyzed descriptively. Investigation of food exposures Given the clustered occurrence of cases, and particularly the nearly simultaneous onset of the three confirmed cases, the hypothesis of a single source of contamination was considered. The investigator conducted systematic interviews with participants and organizers to reconstruct the foods and beverages served during the different meals. Photographs taken during the festivities also helped document the food items consumed. Each food or beverage was classified according to an estimated level of risk based on its origin, method of preparation, and degree of cooking. Industrially processed products and thoroughly cooked foods were considered to present a low risk (Table S1 ). A detailed timeline of the presence of the individuals meeting the case definition was reconstructed for each day of the festivities (Table S2 ). Food items not consumed on those specific days were subsequently excluded from the list of potential exposures. Exposed asymptomatic individuals Because the likely exposure date could only be determined retrospectively, it was not possible to exhaustively identify all exposed individuals. However, ten exposed but asymptomatic individuals underwent serological testing in order to assess the possibility of subclinical or self limiting infection. Environmental investigations Environmental investigations were conducted on site by the investigator and included the search, through witness reports and direct observations, for the presence of rats and mollusks near areas where fruits and vegetables were harvested, as well as near locations used for food preparation and storage (Figure S1 ). Dissection and PCR analysis of mollusks could not be performed at the time of the study because of logistical constraints, particularly difficulties related to transport and sample preservation. No food leftovers could be analyzed more than two weeks after the suspected date of contamination. Only water samples used for the preparation of beverages were therefore subjected to PCR analysis. Laboratory methods Cerebrospinal fluid (CSF) samples from the three hospitalized patients were analyzed by PCR according to the methodology described by Melot et al. [ 11 ]. Water samples (750 mL) were collected from the surface after stirring the bottom of the reservoirs. Samples were examined microscopically before and after centrifugation. PCR analysis was subsequently performed on these samples using the same molecular protocol as that used for the CSF samples. Serological analyses were performed by Western blot at the Swiss Tropical and Public Health Institute (Allschwil, Switzerland) using antigens derived from adult Angiostrongylus cantonensis worms. Detection of the 31-kDa antigenic band by immunoblot has been reported to have high sensitivity and specificity (> 99% each) [ 15 ]. The possibility of cross-reactivity with other endemic parasites ( Toxocara canis , Strongyloides stercoralis ) was also assessed. Ethical considerations The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the New Caledonia Ethics Committee (approval no. 2023-04-001). Written informed consent was waived due to the retrospective nature of the study and the use of anonymized data. Data collection was declared in accordance with the French data protection reference methodology MR-003 of the Commission Nationale de l’Informatique et des Libertés (CNIL) on February 2, 2023. RESULTS Approximately 60 individuals attended the festivities each day. A total of 19 individuals subsequently developed symptoms compatible with neuroangiostrongyliasis. Three cases were classified as confirmed, corresponding to the initially hospitalized patients who underwent lumbar puncture and PCR testing. No additional lumbar punctures were performed among the remaining symptomatic individuals; therefore, no cases were classified as probable and 16 were classified as suspected. Among these suspected cases, 7 were classified as high suspicion (3/3 minor criteria), 8 as moderate suspicion, and 1 as low suspicion. Among the eight moderately suspected cases, six did not present with hypereosinophilia; however, in five of them, eosinophil counts were performed more than 40 days after symptom onset. For the low-suspicion case, neither serology nor blood counts could be performed (Table 1 ). Table 1 Clinical cases CONS : consultation; HOSP : hospitalization; RETRO : retrospective interview. CSF : cerebrospinal fluid; PCR : polymerase chain reaction; NA : not available. AC serology (Angiostrongylus cantonensis) : + weak positive; ++ positive; +++ strongly positive. Study ID Sex Age Case source Symptoms Onset delay (days) CSF PCR CSF eosinophils (cells/mm³) Blood eosinophilia (cells/mm³; day) AC serology Minor criteria Case classification 6S F 48 HOSP Headache, right arm sensory deficit, diarrhea at onset, infectious colitis with systemic inflammation 10 NA NA 0 (day 0) + 2/3 Moderate suspicion 18S F 59 CONS Facial nerve palsy, then headache 12 NA NA 770 (day 1) − (×2) 2/3 Moderate suspicion 1C M 10 HOSP Headache, vomiting, meningeal signs, diarrhea at onset 13 Pos 122 1230 (day 3) +++ 3/3 Confirmed 3C M 27 HOSP Headache, neck pain 14 Pos 1790 760 (day 10) ++ 3/3 Confirmed 2C M 47 HOSP Headache, vomiting, upper limb pain with sensory deficit, diarrhea at onset 14 Pos 5500 1440 (day 2) +++ 3/3 Confirmed 8S F 42 CONS Headache 18 NA NA NA NA 1/2 Low suspicion 7S M 14 CONS Headache, vomiting 18 NA NA 420 (day 53) +++ 2/3 Moderate suspicion 9S M 33 CONS Headache, thigh paresthesia 20 NA NA 560 (day 51) ++ 3/3 High suspicion 5S M 15 CONS Headache, vomiting, migratory limb pain, abdominal pain 20 NA NA 1090 (day 8) + 3/3 High suspicion 4S F 53 CONS Headache, vomiting, migratory back and trunk pain 20 NA NA 980 (day 8) + 3/3 High suspicion 11S M 21 CONS Headache, vomiting 20 NA NA 430 (day 240) ++ 2/3 Moderate suspicion 10S M 26 CONS Headache, vomiting, neck pain 20 NA NA 400 (day 51) + 2/3 Moderate suspicion 12S F 34 RETRO Sciatica-like pain 21 NA NA 810 (day 3) NA 2/2 Moderate suspicion 17S M 26 CONS Headache, vomiting 22 NA NA 540 (day 6) ++ 3/3 High suspicion 14S F 19 CONS Headache 24 NA NA 1450 (day 4) + 3/3 High suspicion 15S F 60 CONS Headache, neck pain 26 NA NA 630 (day 2) +++ 3/3 High suspicion 16S F 24 RETRO Headache, vomiting 29 NA NA 340 (day 42) + 2/3 Moderate suspicion 13S F 8 RETRO Headache 31 NA NA 190 (day 40) + 2/3 Moderate suspicion 19S F 26 CONS Headache 44 NA NA 610 (day 1) +++ 3/3 High suspicion The most frequent manifestation was isolated headache, reported in 16 cases. In some patients, headache was associated with vomiting (n = 9) or with additional neurological symptoms, including paresthesias or erratic pain (n = 4), meningeal signs (n = 1), and facial paralysis (n = 1). Two patients presented with atypical, isolated manifestations: one with atypical sciatica and another with transient, isolated upper limb paralysis (Table 1 , Fig. 2 A). Among the 19 identified cases, three were considered uncertain upon retrospective review (see Discussion). All symptomatic individuals had attended the festivities on December 27th or 28 th, which were therefore considered the most likely exposure period (Table S2 ). The interval between exposure and symptom onset ranged from 2 to 6 weeks, with a median of 3 weeks (IQR: 2–4) (Fig. 2 B). The preliminary food exposure investigation identified five potential candidates (Table S3 ): water drunk directly from a garden hose (Fig. 3 b); lemonade diluted with rainwater; consumption of raw grated green papaya salad ( Carica papaya ); consumption of a fruit known locally as Syzygium malaccense (“Kanak apple”); consumption of a homemade blended fruit juice diluted with rainwater and containing bananas ( Musa spp.), ripe papaya ( Carica papaya ), passion fruit ( Passiflora edulis ), and lemons ( Citrus limon ). Further analysis of food consumption histories and participant timelines progressively narrowed the hypotheses to two possible sources: (i) blended fruit juice diluted with rainwater collected in a large plastic rainwater storage drum (Fig. 3 c). All cases reported having consumed the product, except one. (ii) Lemonade diluted with rainwater from a large concrete rainwater cistern covered with metal sheets, located opposite the festivities shelter (Fig. 3 a), was consumed by all cases. Both beverages were prepared using rainwater stored in non-hermetic containers located close to the food preparation area. The environmental investigation revealed rat traces (feces) and observations of mollusks around both water reservoirs. In the analyzed water samples, no larvae or Angiostrongylus DNA were detected. The blended juices were prepared in a traditional open-air kitchen. Clean dishes, including the blender used for juice preparation, were left to dry outside each evening on a small wall near the food preparation area (Fig. 3 d,e). Numerous gastropods ( Achatina fulica , Laevicaulis alte , Platydemus manokwari ) were observed in the vegetation surrounding the kitchen and occasionally directly on drying utensils, particularly Laevicaulis alte (Fig. 3 g-j). The juice preparation process was further investigated through interviews and reconstruction with the food preparers (Fig. 4 ). This point will be discussed in greater detail in the Discussion section. Serological tests performed nine months after the cluster among ten exposed but asymptomatic individuals were all positive. Among the 27 serological tests performed in this study, 9 (33%) were positive for toxocariasis and one for strongyloidiasis (Fig. 2 d). DISCUSSION With 19 cases, this cluster appears to be among the largest reported to date in the literature [ 16 – 21 ], providing a rare opportunity to explore the mechanisms of transmission of a disease in which the route of contamination often remains unclear. Although the source of infection could not be formally demonstrated, the investigation identified two main hypotheses: contamination of rainwater storage systems and, more likely, contamination of a homemade blended fruit juice prepared during the festivities. Waterborne transmission through rainwater used in beverages Rainwater used to dilute both lemonade and fruit juices could theoretically have been responsible for the contamination. It should be noted that in Lifou, rainwater is frequently preferred to tap water—even though the latter is available in most households—because its chlorinated taste is often perceived as unpleasant. The hypothesis of waterborne contamination has been raised several times in Hawaii, particularly in connection with rainwater catchment systems [ 4 ]. Mollusks are frequently attracted to humid environments and may fall into water tanks, sometimes releasing hundreds of larvae contained in their tissues, which can survive for several days [ 22 ]. However, several observations argue against this hypothesis. When inhabitants collected water from these reservoirs, they generally did so from the surface using a container. The few available studies suggest that larvae are more likely to accumulate at the bottom of the tanks because of sedimentation [ 4 ]. Even if the larvae had been evenly distributed, the large dilution volumes involved (approximately 200 and 20,000 liters) would likely have resulted in an infective dose too low to infect such a large number of individuals. Moreover, since larvae can survive for several days, one would expect the contamination period to extend over several days. This does not appear to have been the case. For instance, two days after the presumed date of contamination, around thirty individuals from neighboring tribes were invited and also consumed the juices and lemonade, yet none developed symptoms. Finally, it should be recalled that waterborne transmission, although biologically plausible, has never been formally demonstrated, except in a few isolated cases [ 4 ]. Contamination of blended fruits by mollusks or flatworms Contamination of the blended fruit juice by mollusks or flatworms prior to dilution appears to be the most likely hypothesis. An association between the consumption of vegetarian smoothies and cases of eosinophilic meningitis has previously been reported in Taiwan [ 18 ]. Two potential routes of contamination can be considered: contamination of the fruits themselves or contamination of kitchen containers and utensils. Three mechanisms are theoretically possible: deposition of contaminated mucus [ 23 ], release of larvae from a drowned mollusk [ 4 ], or the accidental blending of an entire mollusk [ 18 ]. The “contaminating slime trail” hypothesis suggests that infective third-stage larvae (L3) originating from an infected mollusk could be released into its mucus and deposited on a vegetable, a glass, or a kitchen utensil [ 24 ]. Papayas are known to be visited and sometimes damaged by Achatina snails that climb papaya trees to feed on them (Fig. 4 ), and the investigation showed that mollusks circulated freely around and sometimes on kitchen equipment. However, this mechanism remains debated. Experimental studies suggest that the number of L3 larvae present in the mucus of unstressed mollusks is generally too low to represent a sufficient infective dose, particularly considering that the total volume of juice prepared was approximately 10 liters[ 12 , 25 ]. In addition, the fruits used were intact and were carefully washed and peeled before blending (Fig. 4 ). Another hypothesis is the release of larvae by a mollusk that had fallen into the blended juice or the lemonade. This mechanism has been suggested in a cluster reported in the Pacific among individuals consuming kava, a traditional beverage prepared from the roots of the pepper plant [ 4 ]. In that case, a snail was found drowned at the bottom of a traditional wooden bowl ( tanoa ) used for kava preparation. In our cluster, however, it seems unlikely that a mollusk could have escaped the attention of the food preparers. The 3 liters of blended fruits were poured into a large white-bottomed cooler and then diluted with 7 liters of water (Fig. 4 ). The mixture was immediately transferred into transparent 1.5-liter bottles using a funnel and closed with screw caps. Very small specimens might theoretically have gone unnoticed, but the release of larvae from mollusk tissues appears to be uncommon during the first 24 hours, which is much longer than the delay between preparation and consumption of the juice [ 4 ]. It should also be noted that Parmarion martensi , a small slug capable of harboring thousands of larvae, is not present in New Caledonia. Another possibility is that an entire mollusk was accidentally blended. It is known that Achatina snails may climb papaya trees to feed. However, according to the person who prepared the fruits, the papayas were intact and the fruits were peeled and cut before blending (Fig. 4 ). The presence of a mollusk, usually dark in color, within yellow fruit flesh would have been difficult to overlook. The final hypothesis, which we consider the most plausible, is that a mollusk or an other small organism was introduced directly into the blender. The blender and other kitchen utensils were routinely left outside overnight to dry on a low wall near the kitchen, where numerous gastropods were observed. A mollusk or flatworm could therefore have entered the blender lid during the night and remained unnoticed until the preparation of the juice. If subsequently crushed during blending, this could have led to the release of a large number of larvae. Among the organisms that might have escape the attention of the preparers, the flatworm Platydemus manokwari , which is very dark in color and could have been poorly visible on the black lid, may be suspected. This flatworm, which was observed near the areas where dishes were drying, is a predator of mollusks and may, like other planarians, harbor infective L3 larvae [ 22 , 23 , 26 ]. This invasive species has been suspected of contributing to several infections in Japan since its introduction [ 27 ]. It has been present in New Caledonia since the 1990s. It should also be recalled that endemic planarians were previously considered by Ash to be responsible for infections in New Caledonia [ 12 ]. Platydemus manokwari frequently lives close to human dwellings and may enter kitchens or be found on vegetation and kitchen utensils while hunting mollusks [ 26 ]. It is therefore conceivable that an individual hidden in a fold of the blender lid could have gone unnoticed. However, the involvement of a flatworm in this scenario is limited by the issue of infective dose. Infection with Angiostrongylus cantonensis results from ingestion of infective third-stage larvae (L3), and clinical disease is generally associated with the ingestion of multiple larvae. The minimal number of larvae capable of producing symptoms in humans remains unknown [ 23 , 28 ]. In rats, it is estimated to be around 30 larvae, but experimental studies in non-permissive hosts such as pigs or calves suggest that several hundreds or even thousands may be required. Extrapolation to humans therefore remains uncertain. If we assume that the 10 liters of juice (3 liters obtained by blending and 7 liters of added water) were consumed by approximately 40–50 individuals (corresponding to roughly 200–250 ml per person) and that the infective dose is at least around 20 larvae, the crushed mollusk would have needed to contain at least about 1,000 larvae. However, for P. manokwari and other planarians, the highest infestations reported in the literature rarely exceed approximately 200 larvae [ 12 , 26 ]. In contrast, Laevicaulis alte , which was abundant at the site, may harbor very high parasite loads, with reports of up to 8,600 larvae [ 12 ], and could therefore be more likely to produce such a cluster. This order-of-magnitude reasoning suggests that the involvement of a heavily infected gastropod is more plausible than that of a flatworm. Case classification and diagnostic uncertainty In addition to uncertainties related to exposure and diagnostic testing, some limitations regarding case classification should be considered. Upon retrospective review, three cases were considered uncertain. Case 18S, classified as moderately suspected, presented with facial paralysis and hypereosinophilia but had two negative serological tests and reportedly did not consume the blended fruit juice, the most likely source of exposure. Case 6S presented with transient neurological symptoms without eosinophilia, and an alternative diagnosis (partial seizure in the context of infectious colitis) could not be excluded. Finally, for case 19S, once the presumed date of exposure was established, the delay between exposure and symptom onset (44 days) appeared unusually long. However, their inclusion is unlikely to have significantly impacted the overall interpretation of the outbreak. Serological findings Serological results suggest that false-positive reactions remain possible in Lifou, particularly for Toxocara canis . The 33% seropositivity observed in this study (Fig. 2 d) is consistent with toxocariasis serology data from Nouméa Hospital, where a prevalence of approximately 40% has been reported (personal data). However, Angiostrongylus antibodies may also cross-react with Toxocara antigens. Finally, positive serological results among exposed but asymptomatic individuals may reflect either a substantial proportion of asymptomatic infections or a high background seroprevalence resulting from previous exposure. Study limitations Our study has several limitations. This investigation relied on the reasonable assumption of a single source of contamination; however, multiple sources of exposure cannot be excluded. Furthermore, the delay between the suspected exposure and the field investigation, partly related to the long incubation period, may have affected the accuracy of participants’ recollections and limited the relevance of environmental sampling. Information regarding the preparation of the juice was based on the statements of individuals potentially involved in its preparation and may therefore be subject to reporting bias. It was not possible to identify and interview all asymptomatic participants who attended the gatherings on December 27 and 28, or to document their potential consumption of the blended fruit juice, thereby hindering the calculation of an attack rate. Only three lumbar punctures were performed. However, this examination currently represents the only means of confirming the diagnosis or defining a probable case. Because of its invasive nature, it is rarely performed when symptoms are limited to isolated persistent headaches without clear meningeal signs. Moreover, the case definition used to identify possible cases may have limitations in endemic settings, as the presence of a single compatible symptom is sufficient for classification as a possible case. The use of eosinophilia as a minor criterion is also problematic in this setting, where several parasitic infections, particularly hookworm infection, are endemic. Furthermore, eosinophilia was often assessed too late to still be detectable, potentially resulting in underascertainment of this criterion in some cases. The absence of data on the seroprevalence of A. cantonensis in this hotspot of New Caledonia also limits the interpretation of serological results, as positive results may reflect previous exposure in an endemic context. The few available studies suggest that seroprevalence may be high; for example, it has been estimated to reach up to 30% in Hawaii [ 29 ]. Finally, the search for A. cantonensis larvae in mollusks and rats could not be performed at the time of the investigation. However, environmental sampling conducted one year later, including samples collected at the cluster site in December 2024, showed a very high prevalence of A. cantonensis in Achatina fulica (76%, 32/42) as part of the study “Parasitic meningitis due to Angiostrongylus cantonensis in the Pacific: medical awareness and environmental investigation” (preliminary results, unpublished data). CONCLUSION Open-air kitchens commonly used in Melanesian societies may facilitate food contamination by Angiostrongylus cantonensis larvae through the unnoticed presence of small slugs or flatworms on kitchen utensils or food, particularly when food preparation involves shared equipment such as blenders. Serology remains a useful diagnostic tool, but its interpretation is limited by the lack of local seroprevalence data and the possibility of occasional cross-reactivity. This study highlights the diagnostic challenges and the difficulty in determining the route of contamination in this disease, particularly because of its prolonged incubation period and the absence of a simple confirmatory test for mild clinical forms. Taken together, these findings suggest that the accidental blending of a highly infected gastropod may have acted as an amplifying event, facilitating simultaneous exposure of multiple individuals and explaining the occurrence of this cluster. Declarations AUTHORS’CONTRIBUTION: YMD conceived the study. YMD and JC designed the study protocol and coordinated the investigation. JSM conducted the field investigation and took the photographs. YMD, JSM and MB collected the clinical and epidemiological data. YMD, JSM, BN, JC, MP, TM, AB and ABi performed the data analysis and interpretation. YMD drafted the manuscript, designed and created the figures. AD, MP, NM, BN and JC critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript. CONSENT FOR PUBLICATION not applicable. AVAILABILITY OF DATA AND MATERIALS: The datasets generated and/or analysed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. COMPETING INTEREST: none ETHIC STATEMENT: The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the New Caledonia Ethics Committee (approval no. 2023-04-001). Data collection was declared in accordance with the French data protection reference methodology MR-003 of the Commission Nationale de l’Informatique et des Libertés (CNIL) on February 2, 2023. HUMAN ETHICS AND CONSENT TO PARTICIPATE DECLARATIONS : Written informed consent was obtained from all asymptomatic exposed individuals who underwent serological testing. The remainder of the study relied on retrospective analysis of routinely collected clinical data, for which individual consent was not required in accordance with applicable regulations. FUNDING : This study was supported by the Pacific Fund, a French regional cooperation program supporting scientific projects in the Pacific, through the project “Parasitic meningitis due to Angiostrongylus cantonensis in the Pacific: medical awareness and environmental investigation” (Deliberation No. 2017) FINANCIAL DISCLOSURE STATEMENT: The authors declare that they have no conflict of interest. ACKNOWLEDGEMENTS: We sincerely thank all the medical and paramedical staff of the Chepenehé health center, Marie-Rose Waia, Director of DACAS and Raymonde Ultramadra, Head of Health Services in Lifou for their support in this study. We also thank Maguy, Zolie and Lucie for their logistical assistance. We are grateful to Ihage Bako for his help with the field investigation. Finally, we express our deepest gratitude to the small chief and the pastor of the tribe where the study took place, and to all the inhabitants who welcomed, supported, and assisted the investigator. We thank Joelle Hamblin for her careful review and improvement of the English language. References Wang Q-P, Lai D-H, Zhu X-Q, Chen X-G, Lun Z-R. Human angiostrongyliasis. Lancet Infect Dis. 2008;8:621–30. 10.1016/S1473-3099(08)70229-9 . Ansdell V, Kramer KJ, McMillan JK, Gosnell WL, Murphy GS, Meyer BC, et al. Guidelines for the diagnosis and treatment of neuroangiostrongyliasis: updated recommendations. Parasitology. 2021;148:227–33. 10.1017/S0031182020001262 . Turck HC, Fox MT, Cowie RH. Paratenic hosts of Angiostrongylus cantonensis and their relation to human neuroangiostrongyliasis globally. One Health. 2022;15:100426. 10.1016/j.onehlt.2022.100426 . Howe K, Kaluna L, Lozano A, Torres Fischer B, Tagami Y, McHugh R et al. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. Knight M, editor. PLoS ONE. 2019;14: e0209813. 10.1371/journal.pone.0209813 Kliks MM, Palumbo NE. Eosinophilic meningitis beyond the Pacific Basin: The global dispersal of a peridomestic zoonosis caused by angiostrongylus cantonensis, the nematode lungworm of rats. Soc Sci Med. 1992;34:199–212. 10.1016/0277-9536(92)90097-A . Cowie RH, Ansdell V, Panosian Dunavan C, Rollins RL, Neuroangiostrongyliasis. Global Spread of an Emerging Tropical Disease. Am J Trop Med Hyg. 2022;107:1166–72. 10.4269/ajtmh.22-0360 . Jaume-Ramis S, Rivory P, Velázquez IS, Šlapeta J, Paredes‐Esquivel C. Neuroangiostrongyliasis Infection Risk Near Preschool Centres in Mallorca, Spain: A Pilot Micro‐Epidemiological Study. Zoonoses Public Health. 2025;72:515–22. 10.1111/zph.13228 . Pandian D, Šipková A, Scarcelli S, Sgroi G, Kačmaříková J, Buono F, et al. Detection of Rat Lungworm ( Angiostrongylus cantonensis ) in Rats and Gastropods, Italy. Emerg Infect Dis. 2025;31. 10.3201/eid3109.250648 . Rosen L, Loison G, Laigret J, Wallace GD. Studies on eosinophilic meningitis. 3. Epidemiologic and clinical observations on pacific islands and the possible etiologic role of Angiostrongylus cantonensis. Am J Epidemiol. 1967;85:17–44. 10.1093/oxfordjournals.aje.a120673 . Alicata JE. The incidence of angiostrongylus cantonensis among rats and mollusks in new caledonia and nearby islands and its possible relation withe meningitis eosinophilic. Melot B, Delvallez G, Gourinat A-C, Molko N, Goarant C, Ducrot Y-M et al. Eosinophilic meningitis in New Caledonia: The role of Angiostrongylus cantonensis? Schieffelin J, editor. PLoS ONE. 2021;16: e0254964. 10.1371/journal.pone.0254964 Ash LR. Observations on the role of mollusks and planarians in the transmission of Angiostrongylus cantonensis infection to man in new caledonia. Rev Biol Trop. 1976;24:163–74. Mora J-S. Méningite à éosinophiles à Angiostrongylus cantonensis: investigation d’un cluster remarquable de 17 patients dans la tribu de Mucaweng, sur l’île de Lifou, en Nouvelle-Calédonie. Bordeaux. 2025. Available: https://dumas.ccsd.cnrs.fr/dumas-05300150v1/file/Med_generale_2025_Mora.pdf Graeff-Teixeira C, Sawanyawisuth K, Lv S, Sears W, Rodríguez ZG, Álvarez HH, et al. Neuroangiostrongyliasis: Updated Provisional Guidelines for Diagnosis and Case Definitions. Pathogens. 2023;12:624. 10.3390/pathogens12040624 . Eamsobhana P, Gan XX, Ma A, Wang Y, Wanachiwanawin D, Yong HS. Dot immunogold filtration assay (DIGFA) for the rapid detection of specific antibodies against the rat lungworm Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) using purified 31-kDa antigen. J Helminthol. 2014;88:396–401. 10.1017/S0022149X13000321 . Xue DY, Ruan YZ, Lin BC, Zheng RY, Fang JQ, Zhao QX, et al. [Epidemiological investigation on an outbreak of angiostrongyliasis cantonensis in Wenzhou]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2000;18:176–8. Slom TJ, Cortese MM, Gerber SI, Jones RC, Holtz TH, Lopez AS, et al. An Outbreak of Eosinophilic Meningitis Caused by Angiostrongylus cantonensis in Travelers Returning from the Caribbean. N Engl J Med. 2002;346:668–75. 10.1056/NEJMoa012462 . Tsai H-C, Lee SS-J, Huang C-K, Yen C-M, Chen E-R, Liu Y-C. Outbreak of eosinophilic meningitis associated with drinking raw vegetable juice in southern Taiwan. Am J Trop Med Hyg. 2004;71:222–6. 10.4269/ajtmh.2004.71.222 . Malvy D, Ezzedine K, Receveur M-C, Pistone T, Crevon L, Lemardeley P, et al. Cluster of eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in French policemen troop returning from the Pacific Islands. Travel Med Infect Dis. 2008;6:301–4. 10.1016/j.tmaid.2008.06.003 . Lin C-W, Liu Y-L, Lin HZ, Wang R-D, Wei S-T, Wu Y-C, et al. Cluster of Angiostrongylus cantonensis Infection in Tainan County, 2009. Epidemiol Bull. 2010;26. 10.6525/TEB.201002_26(4).0003 . Yang L, Darasavath C, Chang K, Vilay V, Sengduangphachanh A, Adsamouth A, et al. Cluster of Angiostrongyliasis Cases Following Consumption of Raw Monitor Lizard in the Lao People’s Democratic Republic and Review of the Literature. TropicalMed. 2021;6:107. 10.3390/tropicalmed6030107 . Qvarnstrom Y, Bs HSB. Detection of Rat Lungworm in Intermediate, Definitive, and Paratenic Hosts Obtained from Environmental Sources. Public Health. 2013;72. Rollins RL, Medeiros MCI, Cowie RH. Stressed snails release Angiostrongylus cantonensis (rat lungworm) larvae in their slime. One Health. 2023;17:100658. 10.1016/j.onehlt.2023.100658 . Cowie RH. Pathways for Transmission of Angiostrongyliasis and the Risk of Disease Associated with Them. Public Health. 2013;72. Kramer KJ, Posner J, Gosnell WL. Role of Gastropod Mucus in the Transmission of Angiostrongylus cantonensis , a Potentially Serious Neurological Infection. ACS Chem Neurosci. 2018;9:629–32. 10.1021/acschemneuro.7b00491 . Chaisiri K, Dusitsittipon S, Panitvong N, Ketboonlue T, Nuamtanong S, Thaenkham U, et al. Distribution of the newly invasive New Guinea flatworm Platydemus manokwari (Platyhelminthes: Geoplanidae) in Thailand and its potential role as a paratenic host carrying Angiostrongylus malaysiensis larvae. J Helminthol. 2019;93:711–9. 10.1017/S0022149X18000834 . Asato R, Taira K, Nakamura M, Kudaka J, Itokazu K, Kawanaka M. Changing Epidemiology of Angiostrongyliasis Cantonensis in Okinawa Prefecture, Japan. Jpn J Infect Dis. 2004;57:184–6. 10.7883/yoken.JJID.2004.184 . Prociv P, Spratt DM, Carlisle MS. Neuro-angiostrongyliasis: unresolved issues. Int J Parasitol. 2000;30:1295–303. 10.1016/S0020-7519(00)00133-8 . Jarvi SI, Eamsobhana P, Quarta S, Howe K, Jacquier S, Hanlon A, et al. Estimating Human Exposure to Rat Lungworm (Angiostrongylus cantonensis) on Hawai’i Island: A Pilot Study. Am J Trop Med Hyg. 2020;102:69–77. 10.4269/ajtmh.18-0242 . Additional Declarations No competing interests reported. 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Yves-Marie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYBADHiA2ALP4QURCAQlaJCQbQFoMiLMJosXgAJyNQ9mN5MOfbtTck+FnYN4m8XOPTZ3x+dWJHx4YMMjzix3AoSUtTTrnWDGPZANbmWTPszQJsxtvN0sAHWY4c3YCdi1nzpgx57Al8Bgc4DGTZjhwGKjl7AaQlgSD27i0nP/8OedfAo89TIvxjLObf+DVcryHQTq3DWgLA1SLAX/vNry2SB5vM5PO7UvgkTjMVmzZcyBNcsYN3m0WCQYSOP3Cd5j58eecbwn2/O3NG2/8OGDDz99/dvPNHxU28vzS2LUoHICxmGEMCbBKCazKQUC+AUOI/wCG0CgYBaNgFIxsAACLaVxvgYym2wAAAABJRU5ErkJggg==","orcid":"","institution":"Centre Hospitalier Universitaire de La Réunion","correspondingAuthor":true,"prefix":"","firstName":"DUCROT","middleName":"","lastName":"Yves-Marie","suffix":""},{"id":623861501,"identity":"a84dd407-3408-45ec-90d2-a247b6587618","order_by":1,"name":"Jean-Sebastien MORA","email":"","orcid":"","institution":"Province des Iles Loyauté","correspondingAuthor":false,"prefix":"","firstName":"Jean-Sebastien","middleName":"","lastName":"MORA","suffix":""},{"id":623861502,"identity":"340bafd3-3bde-4ebc-b01c-6cbc7c2955c8","order_by":2,"name":"Morgane BAHU","email":"","orcid":"","institution":"Province des Iles Loyauté","correspondingAuthor":false,"prefix":"","firstName":"Morgane","middleName":"","lastName":"BAHU","suffix":""},{"id":623861503,"identity":"babc3079-7177-486d-8a25-449dae4ff743","order_by":3,"name":"Alexandre BOURLES","email":"","orcid":"","institution":"Institut Pasteur de Nouvelle Calédonie","correspondingAuthor":false,"prefix":"","firstName":"Alexandre","middleName":"","lastName":"BOURLES","suffix":""},{"id":623861504,"identity":"06c254c6-0123-4194-9818-2cc7c39e49f1","order_by":4,"name":"Matthieu POT","email":"","orcid":"","institution":"Institut Pasteur de Nouvelle 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Nouvelle-Calédonie","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"MOLKO","suffix":""},{"id":623861510,"identity":"d1076996-ad86-4337-9243-3e6006a4007d","order_by":8,"name":"Alexandre DUVIGNAUD","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"Alexandre","middleName":"","lastName":"DUVIGNAUD","suffix":""},{"id":623861512,"identity":"3637afd1-748d-4083-9e65-33ba4e01d7e8","order_by":9,"name":"Beatrice NICKEL","email":"","orcid":"","institution":"University of Basel","correspondingAuthor":false,"prefix":"","firstName":"Beatrice","middleName":"","lastName":"NICKEL","suffix":""},{"id":623861514,"identity":"887f66ac-8f1f-4b46-aaf9-e8751b55e86f","order_by":10,"name":"Julien COLOT","email":"","orcid":"","institution":"Institut Pasteur de Nouvelle Calédonie","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"COLOT","suffix":""}],"badges":[],"createdAt":"2026-03-30 21:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9272013/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9272013/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107485185,"identity":"9541cb2d-44df-49df-85b2-568c53abb184","added_by":"auto","created_at":"2026-04-22 02:33:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":747883,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of exposure, clinical investigation, and case classification during the angiostrongyliasis cluster in Lifou, New Caledonia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLP\u003c/strong\u003e: lumbar puncture; \u003cstrong\u003eCSF:\u003c/strong\u003e cerebrospinal fluid; \u003cstrong\u003ePCR:\u003c/strong\u003e polymerase chain reaction; \u003cstrong\u003eEo\u003c/strong\u003e: eosinophils; \u003cstrong\u003eSero\u003c/strong\u003e: serology; \u003cstrong\u003eEMR\u003c/strong\u003e: Electronic Medical Record\u003cbr\u003e\n \u003cstrong\u003eConfirmed case\u003c/strong\u003e: symptoms with positive PCR in CSF.\u003cbr\u003e\n \u003cstrong\u003eProbable case\u003c/strong\u003e: symptoms with eosinophilia in CSF (\u0026gt;10%).\u003cbr\u003e\n \u003cstrong\u003eSuspected case\u003c/strong\u003e: symptoms with ≥1 minor criterion (exposure, peripheral eosinophilia \u0026gt;500/mm³, or positive serology).\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/0ce5ad2d1f5f3624b43c1788.png"},{"id":107484908,"identity":"e544bfa9-ec2a-4a03-a936-9596b5f82004","added_by":"auto","created_at":"2026-04-22 02:33:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1118192,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA: Clinical presentation of cases (n=19)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSymptoms are not mutually exclusive. Cervical pain was reported in three patients, including one presenting with meningeal syndrome. Vomiting was reported in nine patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB: Distribution of symptom onset following presumed exposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: sp = evocative symptoms; sero = positive serology for \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e; Eo = blood eosinophilia (\u0026gt;500 cells/mm³).Case classification was defined according to international consensus criteria: confirmed cases required a positive cerebrospinal fluid (CSF) PCR; probable cases met clinical criteria with CSF eosinophilia and supporting evidence; suspected cases were classified based on the number of minor criteria (exposure, eosinophilia, serology). The majority of cases occurred between weeks 2 and 4, with a peak at week 3, consistent with the expected incubation period of angiostrongyliasis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC: Serological response to \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eAngiostrongylus cantonensis\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e among symptomatic and asymptomatic individuals\u003c/strong\u003e. Serological results among symptomatic and exposed asymptomatic individuals. Black bars represent positive results and white bars represent negative results. Numbers within bars indicate counts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD: Serological results for \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eToxocara spp.\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e and \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eStrongyloides spp.\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e among all tested individuals (potential cross-reactivity).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerological results for Toxocara spp. and Strongyloides spp. are presented for all individuals tested; brown indicates positive results and white indicates negative results.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/8b4058c5c02495132a862e1b.png"},{"id":107484716,"identity":"b046233c-dc77-4b3e-8580-ba3b888ee032","added_by":"auto","created_at":"2026-04-22 02:32:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":5323960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEnvironmental investigation and potential sources of contamination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Large rainwater storage tank located next to the shelter where the festivities took place. Participants collected water from this tank for drinking at the table and for preparing lemonade. Water was collected from the surface using the pot visible in the photograph;(b) End of a garden hose lying directly on the ground, supplied with treated borehole water. Individuals, particularly those engaged in physical activity during the day, drank directly from it; (c) Rainwater collection barrel located at the home of the person who prepared the juices, from which approximately 7 liters of water were taken to dilute the blended fruits; (d) Area adjacent to the traditional Melanesian kitchen where washed dishes were left to dry on a low wall; dishwashing was performed at the washing area visible on the right; (e) Three-dimensional reconstruction illustrating the open kitchen environment within dense vegetation, including the outdoor dishwashing area (left) and the wall used for drying utensils; (f) The two blender bowls (one white, one black) placed on the wall and left to dry after washing; (g–h) \u003cem\u003eAchatina fulica\u003c/em\u003e snails and \u003cem\u003ePlatydemus manokwari\u003c/em\u003eflatworms observed in the vegetation surrounding the kitchen and dishwashing/drying areas; (i–j) \u003cem\u003eLaevicaulis alte \u003c/em\u003eslugs observed on dishes drying on the wall.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/fd4da1ff4c936cadc1e642d3.png"},{"id":107257366,"identity":"da6bf2b9-b589-4d3d-9974-9b531e8e44e6","added_by":"auto","created_at":"2026-04-19 12:28:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2367397,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReconstruction of fruit juice preparation and potential contamination pathways leading to infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eP1–P7, W1, B1 ,L1 depict the preparation of the fruit juice: papayas were washed, peeled, cut, and blended before being diluted with rainwater (W1) and bottled. Bananas ( B1) were processed similarly, and lime juice (L1) was added.\u003c/p\u003e\n\u003cp\u003ePotential contamination routes are indicated: contamination of fruits (C1A–C1B), utensils during drying (C2A–C2B) and blender lid (C3), introduction of a slug into the cooler (C4), or contamination of rainwater (C5), all potentially leading to dissemination of infective L3 larvae.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/d8dbd591a78e13601538dbf8.png"},{"id":107487284,"identity":"e534b265-c2c7-467c-9000-e945224052e8","added_by":"auto","created_at":"2026-04-22 02:40:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10401274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/bd269d1f-45a7-4e64-b639-2bcf362d9bd4.pdf"},{"id":107483147,"identity":"5412e3c3-4041-443d-ba41-435ecfc3603d","added_by":"auto","created_at":"2026-04-22 02:26:35","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15111,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfileslegends.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/cebfe9ec03c494b8ad58e78e.docx"},{"id":107257361,"identity":"4d170cf7-337b-4639-a103-b48a20757cd3","added_by":"auto","created_at":"2026-04-19 12:28:45","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":20775,"visible":true,"origin":"","legend":"","description":"","filename":"additionalFile1tableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/f14f1068714338829237df68.docx"},{"id":107482483,"identity":"26766555-4420-447d-ba40-bf0b6e029c3c","added_by":"auto","created_at":"2026-04-22 02:23:41","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":22386,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile2tableS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/24e1ed98788323b33390c8f8.docx"},{"id":107483438,"identity":"156c8b2a-c3a6-46e7-8377-e433891e6ffc","added_by":"auto","created_at":"2026-04-22 02:27:44","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":20063,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile3tableS3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/fcc980309c1fe55bd940198b.docx"},{"id":107257369,"identity":"918a5a2f-3b41-470f-a2c1-45eb15777ada","added_by":"auto","created_at":"2026-04-19 12:28:45","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1390276,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile4figureS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272013/v1/e334fa61f86fd8af0cc9173a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cluster of 19 Cases of Eosinophilic Meningitis due to Angiostrongylus cantonensis in Lifou, New Caledonia: An Outbreak Investigation","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAngiostrongylus cantonensis (AC), the rat lungworm can accidentally infect humans, leading to a clinical syndrome known as eosinophilic meningitis (EM). After an incubation period typically ranging from 6 to 35 day [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the disease most often presents with persistent headaches, erratic pain in the spine and limbs, and occasionally motor or sensory deficits or mild meningeal signs. Cerebrospinal fluid (CSF) analysis typically reveals eosinophilic pleocytosis. These manifestations result from the migration of larvae in the central nervous system, where they eventually die. In cases of severe infection, the associated inflammatory reaction may lead to neurological sequelae, impaired consciousness, or even death [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Current treatment recommendations favor early administration of corticosteroids combined with albendazole for approximately two weeks [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe life cycle of \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e involves mollusks as intermediate hosts, which become infected by ingesting rat feces containing first-stage larvae. Within the mollusk tissues, larvae develop into infective third-stage larvae. The cycle is completed when rats consume infected mollusks. Larvae may also be transferred to other animals such as planarians, lizards, or crustaceans, which act as paratenic hosts [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHuman infection is usually associated with the intentional or accidental consumption of raw or undercooked mollusks or paratenic hosts. However, contamination of fresh produce or beverages through contact with infected mollusks has also been suggested [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEosinophilic meningitis due to \u003cem\u003eA. cantonensis\u003c/em\u003e is considered an emerging disease originally described in Southeast Asia. Since the 1940s, it has progressively spread throughout the Pacific region, likely due to the dispersal of infected rats transported on commercial and military ships [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The parasite is now reported in several regions worldwide, including Europe [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNew Caledonia is a French overseas territory of approximately 280,000 inhabitants located between Australia and Fiji. It was among the first Pacific territories affected during this geographic expansion [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Currently, around ten sporadic cases are diagnosed annually, mainly among Melanesian populations living in rural areas and typically during the end of the cool and dry season [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The exact mode of contamination is rarely identified. In 1976, Ash suggested that terrestrial flatworms might play a role in transmission during the harvesting season of raw vegetables, possibly explaining the marked seasonality observed in New Caledonia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn January 2023, three inhabitants of a small village in New Caledonia were hospitalized for neuroangiostrongyliasis. All of which had participated in several days of community festivities during the Christmas period. Other attendees also reported symptoms compatible with the infection. An epidemiological investigation of this cluster was therefore initiated [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e"},{"header":"POPULATION AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSetting\u003c/h2\u003e \u003cp\u003eThe investigated village is located on Lifou Island, part of the Loyalty Islands in New Caledonia. Lifou is the largest island of the Loyalty Islands Province and lies approximately 190 km east of the main island of New Caledonia. The village has approximately 80 inhabitants.\u003c/p\u003e \u003cp\u003eLifou Island has a population of about 9,800 people, predominantly Melanesian, whose lifestyle still preserves important traditional elements organized around customary practices, yam cultivation, and religion.\u003c/p\u003e \u003cp\u003eHousing mainly consists of wooden or corrugated metal constructions, with separate buildings for kitchens, sanitary facilities, and traditional thatched huts. Most households have access to electricity and running water.\u003c/p\u003e \u003cp\u003eThe region has a tropical maritime climate characterized by a hot and rainy season from November to April and a cooler and drier season from May to October.\u003c/p\u003e \u003cp\u003eTwo primary healthcare centers are located on the island; however, in case of medical or surgical emergencies, patients are transferred to the territorial hospital located in Noum\u0026eacute;a.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEpidemiological and environmental investigation\u003c/h3\u003e\n\u003cp\u003eThe investigation began approximately one month after the suspected exposure period and was therefore largely retrospective, relying on medical records and participant interviews. The main difficulty was that the festivities had taken place over an entire week, with meals and activities organized both morning and evening.\u003c/p\u003e\n\u003ch3\u003eCase identification\u003c/h3\u003e\n\u003cp\u003eFor the three hospitalized and confirmed cases, detailed hospital records were retrieved. Electronic medical records of residents who had consulted at the nearest health center between one and six weeks after the end of the festivities were systematically reviewed to identify symptoms compatible with neuroangiostrongyliasis.\u003c/p\u003e \u003cp\u003eIn addition, an investigator visited the village for several days to interview the majority of participants and identify potential cases who had not sought medical care (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eCase definition\u003c/h3\u003e\n\u003cp\u003eCase definitions were based on the criteria proposed by the International Angiostrongylus and Angiostrongyliasis Alliance [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eA confirmed case\u003c/b\u003e was defined as the presence of compatible symptoms together with a positive PCR for \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e in cerebrospinal fluid (CSF).\u003c/p\u003e \u003cp\u003e \u003cb\u003eA probable case\u003c/b\u003e was defined as compatible symptoms associated with eosinophilic meningitis and at least two minor criteria (compatible exposure, positive serology, or peripheral blood eosinophilia).\u003c/p\u003e \u003cp\u003e \u003cb\u003eA suspected case\u003c/b\u003e was defined as compatible symptoms together with at least one minor criterion.\u003c/p\u003e \u003cp\u003eThe minor exposure criterion corresponded to participation in meals during the festivities. Because this exposure criterion alone could classify a symptomatic individual as a suspected case, we further stratified suspected cases according to the presence of additional minor criteria, namely peripheral eosinophilia (\u0026gt;\u0026thinsp;500/mm\u0026sup3;) and/or positive serology.\u003c/p\u003e \u003cp\u003eSuspected cases were therefore categorized as follows: \u0026bull; low suspicion: 1 of 3 criteria \u0026bull; moderate suspicion: 2 of 3 criteria \u0026bull; high suspicion: 3 of 3 criteria\u003c/p\u003e \u003cp\u003eThis additional stratification was introduced for descriptive purposes and to better reflect the level of diagnostic probability among suspected cases.\u003c/p\u003e\n\u003ch3\u003eClinical and epidemiological analysis\u003c/h3\u003e\n\u003cp\u003eA weekly epidemic curve was constructed based on the reported dates of symptom onset and the presumed date of exposure. Because the exact dates of symptom onset were sometimes uncertain, the week was used as the unit of time. The frequency of clinical manifestations was analyzed descriptively.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eInvestigation of food exposures\u003c/h2\u003e \u003cp\u003eGiven the clustered occurrence of cases, and particularly the nearly simultaneous onset of the three confirmed cases, the hypothesis of a single source of contamination was considered.\u003c/p\u003e \u003cp\u003e The investigator conducted systematic interviews with participants and organizers to reconstruct the foods and beverages served during the different meals. Photographs taken during the festivities also helped document the food items consumed.\u003c/p\u003e \u003cp\u003eEach food or beverage was classified according to an estimated level of risk based on its origin, method of preparation, and degree of cooking. Industrially processed products and thoroughly cooked foods were considered to present a low risk (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA detailed timeline of the presence of the individuals meeting the case definition was reconstructed for each day of the festivities (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Food items not consumed on those specific days were subsequently excluded from the list of potential exposures.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExposed asymptomatic individuals\u003c/h3\u003e\n\u003cp\u003eBecause the likely exposure date could only be determined retrospectively, it was not possible to exhaustively identify all exposed individuals. However, ten exposed but asymptomatic individuals underwent serological testing in order to assess the possibility of subclinical or self limiting infection.\u003c/p\u003e\n\u003ch3\u003eEnvironmental investigations\u003c/h3\u003e\n\u003cp\u003eEnvironmental investigations were conducted on site by the investigator and included the search, through witness reports and direct observations, for the presence of rats and mollusks near areas where fruits and vegetables were harvested, as well as near locations used for food preparation and storage (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDissection and PCR analysis of mollusks could not be performed at the time of the study because of logistical constraints, particularly difficulties related to transport and sample preservation.\u003c/p\u003e \u003cp\u003eNo food leftovers could be analyzed more than two weeks after the suspected date of contamination. Only water samples used for the preparation of beverages were therefore subjected to PCR analysis.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory methods\u003c/h2\u003e \u003cp\u003eCerebrospinal fluid (CSF) samples from the three hospitalized patients were analyzed by PCR according to the methodology described by Melot et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWater samples (750 mL) were collected from the surface after stirring the bottom of the reservoirs. Samples were examined microscopically before and after centrifugation. PCR analysis was subsequently performed on these samples using the same molecular protocol as that used for the CSF samples.\u003c/p\u003e \u003cp\u003eSerological analyses were performed by Western blot at the Swiss Tropical and Public Health Institute (Allschwil, Switzerland) using antigens derived from adult \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e worms. Detection of the 31-kDa antigenic band by immunoblot has been reported to have high sensitivity and specificity (\u0026gt;\u0026thinsp;99% each) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The possibility of cross-reactivity with other endemic parasites (\u003cem\u003eToxocara canis\u003c/em\u003e, \u003cem\u003eStrongyloides stercoralis\u003c/em\u003e) was also assessed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003e The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the New Caledonia Ethics Committee (approval no. 2023-04-001). Written informed consent was waived due to the retrospective nature of the study and the use of anonymized data. Data collection was declared in accordance with the French data protection reference methodology MR-003 of the Commission Nationale de l\u0026rsquo;Informatique et des Libert\u0026eacute;s (CNIL) on February 2, 2023.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eApproximately 60 individuals attended the festivities each day. A total of 19 individuals subsequently developed symptoms compatible with neuroangiostrongyliasis. Three cases were classified as confirmed, corresponding to the initially hospitalized patients who underwent lumbar puncture and PCR testing. No additional lumbar punctures were performed among the remaining symptomatic individuals; therefore, no cases were classified as probable and 16 were classified as suspected. Among these suspected cases, 7 were classified as high suspicion (3/3 minor criteria), 8 as moderate suspicion, and 1 as low suspicion. Among the eight moderately suspected cases, six did not present with hypereosinophilia; however, in five of them, eosinophil counts were performed more than 40 days after symptom onset. For the low-suspicion case, neither serology nor blood counts could be performed (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eClinical cases CONS\u003c/b\u003e: consultation; \u003cb\u003eHOSP\u003c/b\u003e: hospitalization; \u003cb\u003eRETRO\u003c/b\u003e: retrospective interview.\u003c/p\u003e \u003cp\u003e\u003cb\u003eCSF\u003c/b\u003e: cerebrospinal fluid; \u003cb\u003ePCR\u003c/b\u003e: polymerase chain reaction; \u003cb\u003eNA\u003c/b\u003e: not available.\u003c/p\u003e \u003cp\u003e\u003cb\u003eAC serology (Angiostrongylus cantonensis)\u003c/b\u003e: + weak positive; ++ positive; +++ strongly positive.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCase source\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOnset delay (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCSF PCR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCSF eosinophils (cells/mm\u0026sup3;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBlood eosinophilia (cells/mm\u0026sup3;; day)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAC serology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eMinor criteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCase classification\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHOSP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, right arm sensory deficit, diarrhea at onset, infectious colitis with systemic inflammation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0 (day 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eFacial nerve palsy, then headache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e770\u003c/b\u003e (day 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026minus; (\u0026times;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHOSP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting, meningeal signs, diarrhea at onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e1230\u003c/b\u003e (day 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eConfirmed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHOSP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, neck pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e760\u003c/b\u003e (day 10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eConfirmed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHOSP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting, upper limb pain with sensory deficit, diarrhea at onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e1440\u003c/b\u003e (day 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eConfirmed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLow suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e420 (day 53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, thigh paresthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e560\u003c/b\u003e (day 51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting, migratory limb pain, abdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e1090\u003c/b\u003e (day 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting, migratory back and trunk pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e980\u003c/b\u003e (day 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e430 (day 240)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting, neck pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e400 (day 51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRETRO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eSciatica-like pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e810\u003c/b\u003e (day 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e540\u003c/b\u003e (day 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e1450\u003c/b\u003e (day 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, neck pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e630\u003c/b\u003e (day 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRETRO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache, vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e340 (day 42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRETRO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e190 (day 40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e610\u003c/b\u003e (day 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHigh suspicion\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe most frequent manifestation was isolated headache, reported in 16 cases. In some patients, headache was associated with vomiting (n\u0026thinsp;=\u0026thinsp;9) or with additional neurological symptoms, including paresthesias or erratic pain (n\u0026thinsp;=\u0026thinsp;4), meningeal signs (n\u0026thinsp;=\u0026thinsp;1), and facial paralysis (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003eTwo patients presented with atypical, isolated manifestations: one with atypical sciatica and another with transient, isolated upper limb paralysis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Among the 19 identified cases, three were considered uncertain upon retrospective review (see Discussion).\u003c/p\u003e \u003cp\u003eAll symptomatic individuals had attended the festivities on December 27th or 28 th, which were therefore considered the most likely exposure period (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). The interval between exposure and symptom onset ranged from 2 to 6 weeks, with a median of 3 weeks (IQR: 2\u0026ndash;4) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eThe preliminary food exposure investigation identified five potential candidates (Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e):\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ewater drunk directly from a garden hose (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eb);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003elemonade diluted with rainwater;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003econsumption of raw grated green papaya salad (\u003cem\u003eCarica papaya\u003c/em\u003e);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003econsumption of a fruit known locally as \u003cem\u003eSyzygium malaccense\u003c/em\u003e (\u0026ldquo;Kanak apple\u0026rdquo;);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003econsumption of a homemade blended fruit juice diluted with rainwater and containing bananas (\u003cem\u003eMusa\u003c/em\u003e spp.), ripe papaya (\u003cem\u003eCarica papaya\u003c/em\u003e), passion fruit (\u003cem\u003ePassiflora edulis\u003c/em\u003e), and lemons (\u003cem\u003eCitrus limon\u003c/em\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFurther analysis of food consumption histories and participant timelines progressively narrowed the hypotheses to two possible sources: (i) blended fruit juice diluted with rainwater collected in a large plastic rainwater storage drum (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). All cases reported having consumed the product, except one. (ii) Lemonade diluted with rainwater from a large concrete rainwater cistern covered with metal sheets, located opposite the festivities shelter (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ea), was consumed by all cases.\u003c/p\u003e \u003cp\u003eBoth beverages were prepared using rainwater stored in non-hermetic containers located close to the food preparation area.\u003c/p\u003e \u003cp\u003eThe environmental investigation revealed rat traces (feces) and observations of mollusks around both water reservoirs. In the analyzed water samples, no larvae or \u003cem\u003eAngiostrongylus\u003c/em\u003e DNA were detected.\u003c/p\u003e \u003cp\u003eThe blended juices were prepared in a traditional open-air kitchen. Clean dishes, including the blender used for juice preparation, were left to dry outside each evening on a small wall near the food preparation area (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ed,e). Numerous gastropods (\u003cem\u003eAchatina fulica\u003c/em\u003e, \u003cem\u003eLaevicaulis alte\u003c/em\u003e, \u003cem\u003ePlatydemus manokwari\u003c/em\u003e) were observed in the vegetation surrounding the kitchen and occasionally directly on drying utensils, particularly \u003cem\u003eLaevicaulis alte\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eg-j).\u003c/p\u003e \u003cp\u003eThe juice preparation process was further investigated through interviews and reconstruction with the food preparers (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This point will be discussed in greater detail in the Discussion section.\u003c/p\u003e \u003cp\u003eSerological tests performed nine months after the cluster among ten exposed but asymptomatic individuals were all positive. Among the 27 serological tests performed in this study, 9 (33%) were positive for toxocariasis and one for strongyloidiasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eWith 19 cases, this cluster appears to be among the largest reported to date in the literature [\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], providing a rare opportunity to explore the mechanisms of transmission of a disease in which the route of contamination often remains unclear.\u003c/p\u003e \u003cp\u003eAlthough the source of infection could not be formally demonstrated, the investigation identified two main hypotheses: contamination of rainwater storage systems and, more likely, contamination of a homemade blended fruit juice prepared during the festivities.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eWaterborne transmission through rainwater used in beverages\u003c/h2\u003e \u003cp\u003eRainwater used to dilute both lemonade and fruit juices could theoretically have been responsible for the contamination. It should be noted that in Lifou, rainwater is frequently preferred to tap water\u0026mdash;even though the latter is available in most households\u0026mdash;because its chlorinated taste is often perceived as unpleasant.\u003c/p\u003e \u003cp\u003eThe hypothesis of waterborne contamination has been raised several times in Hawaii, particularly in connection with rainwater catchment systems [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Mollusks are frequently attracted to humid environments and may fall into water tanks, sometimes releasing hundreds of larvae contained in their tissues, which can survive for several days [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, several observations argue against this hypothesis. When inhabitants collected water from these reservoirs, they generally did so from the surface using a container. The few available studies suggest that larvae are more likely to accumulate at the bottom of the tanks because of sedimentation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Even if the larvae had been evenly distributed, the large dilution volumes involved (approximately 200 and 20,000 liters) would likely have resulted in an infective dose too low to infect such a large number of individuals.\u003c/p\u003e \u003cp\u003eMoreover, since larvae can survive for several days, one would expect the contamination period to extend over several days. This does not appear to have been the case. For instance, two days after the presumed date of contamination, around thirty individuals from neighboring tribes were invited and also consumed the juices and lemonade, yet none developed symptoms.\u003c/p\u003e \u003cp\u003eFinally, it should be recalled that waterborne transmission, although biologically plausible, has never been formally demonstrated, except in a few isolated cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eContamination of blended fruits by mollusks or flatworms\u003c/h2\u003e \u003cp\u003eContamination of the blended fruit juice by mollusks or flatworms prior to dilution appears to be the most likely hypothesis. An association between the consumption of vegetarian smoothies and cases of eosinophilic meningitis has previously been reported in Taiwan [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwo potential routes of contamination can be considered: contamination of the fruits themselves or contamination of kitchen containers and utensils. Three mechanisms are theoretically possible: deposition of contaminated mucus [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], release of larvae from a drowned mollusk [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], or the accidental blending of an entire mollusk [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe \u0026ldquo;contaminating slime trail\u0026rdquo; hypothesis suggests that infective third-stage larvae (L3) originating from an infected mollusk could be released into its mucus and deposited on a vegetable, a glass, or a kitchen utensil [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Papayas are known to be visited and sometimes damaged by \u003cem\u003eAchatina\u003c/em\u003e snails that climb papaya trees to feed on them (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e), and the investigation showed that mollusks circulated freely around and sometimes on kitchen equipment. However, this mechanism remains debated. Experimental studies suggest that the number of L3 larvae present in the mucus of unstressed mollusks is generally too low to represent a sufficient infective dose, particularly considering that the total volume of juice prepared was approximately 10 liters[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In addition, the fruits used were intact and were carefully washed and peeled before blending (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother hypothesis is the release of larvae by a mollusk that had fallen into the blended juice or the lemonade. This mechanism has been suggested in a cluster reported in the Pacific among individuals consuming kava, a traditional beverage prepared from the roots of the pepper plant [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In that case, a snail was found drowned at the bottom of a traditional wooden bowl (\u003cem\u003etanoa\u003c/em\u003e) used for kava preparation. In our cluster, however, it seems unlikely that a mollusk could have escaped the attention of the food preparers. The 3 liters of blended fruits were poured into a large white-bottomed cooler and then diluted with 7 liters of water (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The mixture was immediately transferred into transparent 1.5-liter bottles using a funnel and closed with screw caps. Very small specimens might theoretically have gone unnoticed, but the release of larvae from mollusk tissues appears to be uncommon during the first 24 hours, which is much longer than the delay between preparation and consumption of the juice [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It should also be noted that \u003cem\u003eParmarion martensi\u003c/em\u003e, a small slug capable of harboring thousands of larvae, is not present in New Caledonia.\u003c/p\u003e \u003cp\u003eAnother possibility is that an entire mollusk was accidentally blended. It is known that \u003cem\u003eAchatina\u003c/em\u003e snails may climb papaya trees to feed. However, according to the person who prepared the fruits, the papayas were intact and the fruits were peeled and cut before blending (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The presence of a mollusk, usually dark in color, within yellow fruit flesh would have been difficult to overlook.\u003c/p\u003e \u003cp\u003eThe final hypothesis, which we consider the most plausible, is that a mollusk or an other small organism was introduced directly into the blender. The blender and other kitchen utensils were routinely left outside overnight to dry on a low wall near the kitchen, where numerous gastropods were observed. A mollusk or flatworm could therefore have entered the blender lid during the night and remained unnoticed until the preparation of the juice. If subsequently crushed during blending, this could have led to the release of a large number of larvae.\u003c/p\u003e \u003cp\u003eAmong the organisms that might have escape the attention of the preparers, the flatworm \u003cem\u003ePlatydemus manokwari\u003c/em\u003e, which is very dark in color and could have been poorly visible on the black lid, may be suspected. This flatworm, which was observed near the areas where dishes were drying, is a predator of mollusks and may, like other planarians, harbor infective L3 larvae [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This invasive species has been suspected of contributing to several infections in Japan since its introduction [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. It has been present in New Caledonia since the 1990s. It should also be recalled that endemic planarians were previously considered by Ash to be responsible for infections in New Caledonia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003ePlatydemus manokwari\u003c/em\u003e frequently lives close to human dwellings and may enter kitchens or be found on vegetation and kitchen utensils while hunting mollusks [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. It is therefore conceivable that an individual hidden in a fold of the blender lid could have gone unnoticed.\u003c/p\u003e \u003cp\u003eHowever, the involvement of a flatworm in this scenario is limited by the issue of infective dose. Infection with \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e results from ingestion of infective third-stage larvae (L3), and clinical disease is generally associated with the ingestion of multiple larvae. The minimal number of larvae capable of producing symptoms in humans remains unknown [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In rats, it is estimated to be around 30 larvae, but experimental studies in non-permissive hosts such as pigs or calves suggest that several hundreds or even thousands may be required. Extrapolation to humans therefore remains uncertain.\u003c/p\u003e \u003cp\u003eIf we assume that the 10 liters of juice (3 liters obtained by blending and 7 liters of added water) were consumed by approximately 40\u0026ndash;50 individuals (corresponding to roughly 200\u0026ndash;250 ml per person) and that the infective dose is at least around 20 larvae, the crushed mollusk would have needed to contain at least about 1,000 larvae. However, for \u003cem\u003eP. manokwari\u003c/em\u003e and other planarians, the highest infestations reported in the literature rarely exceed approximately 200 larvae [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, \u003cem\u003eLaevicaulis alte\u003c/em\u003e, which was abundant at the site, may harbor very high parasite loads, with reports of up to 8,600 larvae [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and could therefore be more likely to produce such a cluster. This order-of-magnitude reasoning suggests that the involvement of a heavily infected gastropod is more plausible than that of a flatworm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCase classification and diagnostic uncertainty\u003c/h2\u003e \u003cp\u003eIn addition to uncertainties related to exposure and diagnostic testing, some limitations regarding case classification should be considered.\u003c/p\u003e \u003cp\u003eUpon retrospective review, three cases were considered uncertain. Case 18S, classified as moderately suspected, presented with facial paralysis and hypereosinophilia but had two negative serological tests and reportedly did not consume the blended fruit juice, the most likely source of exposure. Case 6S presented with transient neurological symptoms without eosinophilia, and an alternative diagnosis (partial seizure in the context of infectious colitis) could not be excluded. Finally, for case 19S, once the presumed date of exposure was established, the delay between exposure and symptom onset (44 days) appeared unusually long.\u003c/p\u003e \u003cp\u003eHowever, their inclusion is unlikely to have significantly impacted the overall interpretation of the outbreak.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eSerological findings\u003c/h2\u003e \u003cp\u003eSerological results suggest that false-positive reactions remain possible in Lifou, particularly for \u003cem\u003eToxocara canis\u003c/em\u003e. The 33% seropositivity observed in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ed) is consistent with toxocariasis serology data from Noum\u0026eacute;a Hospital, where a prevalence of approximately 40% has been reported (personal data). However, \u003cem\u003eAngiostrongylus\u003c/em\u003e antibodies may also cross-react with \u003cem\u003eToxocara\u003c/em\u003e antigens.\u003c/p\u003e \u003cp\u003eFinally, positive serological results among exposed but asymptomatic individuals may reflect either a substantial proportion of asymptomatic infections or a high background seroprevalence resulting from previous exposure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eStudy limitations\u003c/h2\u003e \u003cp\u003eOur study has several limitations.\u003c/p\u003e \u003cp\u003eThis investigation relied on the reasonable assumption of a single source of contamination; however, multiple sources of exposure cannot be excluded.\u003c/p\u003e \u003cp\u003eFurthermore, the delay between the suspected exposure and the field investigation, partly related to the long incubation period, may have affected the accuracy of participants\u0026rsquo; recollections and limited the relevance of environmental sampling.\u003c/p\u003e \u003cp\u003eInformation regarding the preparation of the juice was based on the statements of individuals potentially involved in its preparation and may therefore be subject to reporting bias.\u003c/p\u003e \u003cp\u003e It was not possible to identify and interview all asymptomatic participants who attended the gatherings on December 27 and 28, or to document their potential consumption of the blended fruit juice, thereby hindering the calculation of an attack rate.\u003c/p\u003e \u003cp\u003eOnly three lumbar punctures were performed. However, this examination currently represents the only means of confirming the diagnosis or defining a probable case. Because of its invasive nature, it is rarely performed when symptoms are limited to isolated persistent headaches without clear meningeal signs. Moreover, the case definition used to identify possible cases may have limitations in endemic settings, as the presence of a single compatible symptom is sufficient for classification as a possible case.\u003c/p\u003e \u003cp\u003eThe use of eosinophilia as a minor criterion is also problematic in this setting, where several parasitic infections, particularly hookworm infection, are endemic. Furthermore, eosinophilia was often assessed too late to still be detectable, potentially resulting in underascertainment of this criterion in some cases.\u003c/p\u003e \u003cp\u003eThe absence of data on the seroprevalence of \u003cem\u003eA. cantonensis\u003c/em\u003e in this hotspot of New Caledonia also limits the interpretation of serological results, as positive results may reflect previous exposure in an endemic context. The few available studies suggest that seroprevalence may be high; for example, it has been estimated to reach up to 30% in Hawaii [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFinally, the search for \u003cem\u003eA. cantonensis\u003c/em\u003e larvae in mollusks and rats could not be performed at the time of the investigation. However, environmental sampling conducted one year later, including samples collected at the cluster site in December 2024, showed a very high prevalence of \u003cem\u003eA. cantonensis\u003c/em\u003e in \u003cem\u003eAchatina fulica\u003c/em\u003e (76%, 32/42) as part of the study \u0026ldquo;Parasitic meningitis due to \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e in the Pacific: medical awareness and environmental investigation\u0026rdquo; (preliminary results, unpublished data).\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOpen-air kitchens commonly used in Melanesian societies may facilitate food contamination by \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e larvae through the unnoticed presence of small slugs or flatworms on kitchen utensils or food, particularly when food preparation involves shared equipment such as blenders.\u003c/p\u003e \u003cp\u003eSerology remains a useful diagnostic tool, but its interpretation is limited by the lack of local seroprevalence data and the possibility of occasional cross-reactivity.\u003c/p\u003e \u003cp\u003eThis study highlights the diagnostic challenges and the difficulty in determining the route of contamination in this disease, particularly because of its prolonged incubation period and the absence of a simple confirmatory test for mild clinical forms.\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that the accidental blending of a highly infected gastropod may have acted as an amplifying event, facilitating simultaneous exposure of multiple individuals and explaining the occurrence of this cluster.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHORS\u0026rsquo;CONTRIBUTION: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYMD conceived the study. YMD and JC designed the study protocol and coordinated the investigation. JSM conducted the field investigation and took the photographs. YMD, JSM and MB collected the clinical and epidemiological data. YMD, JSM, BN, JC, MP, TM, AB and ABi performed the data analysis and interpretation. YMD drafted the manuscript, designed and created the figures. AD, MP, NM, BN and JC critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\n\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION \u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS: \u003c/strong\u003eThe datasets generated and/or analysed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTEREST: \u003c/strong\u003enone\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eETHIC STATEMENT:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the New Caledonia Ethics Committee (approval no. 2023-04-001). Data collection was declared in accordance with the French data protection reference methodology MR-003 of the Commission Nationale de l\u0026rsquo;Informatique et des Libert\u0026eacute;s (CNIL) on February 2, 2023.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHUMAN ETHICS AND CONSENT TO PARTICIPATE DECLARATIONS\u003c/strong\u003e: \u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all asymptomatic exposed individuals who underwent serological testing. The remainder of the study relied on retrospective analysis of routinely collected clinical data, for which individual consent was not required in accordance with applicable regulations.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFUNDING : \u003c/strong\u003eThis study was supported by the Pacific Fund, a French regional cooperation program supporting scientific projects in the Pacific, through the project \u0026ldquo;Parasitic meningitis due to \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e in the Pacific: medical awareness and environmental investigation\u0026rdquo; (Deliberation No. 2017)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFINANCIAL DISCLOSURE STATEMENT:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank all the medical and paramedical staff of the Chepeneh\u0026eacute; health center, Marie-Rose Waia, Director of DACAS and Raymonde Ultramadra, Head of Health Services in Lifou for their support in this study. We also thank Maguy, Zolie and Lucie for their logistical assistance. We are grateful to Ihage Bako for his help with the field investigation. Finally, we express our deepest gratitude to the small chief and the pastor of the tribe where the study took place, and to all the inhabitants who welcomed, supported, and assisted the investigator. We thank Joelle Hamblin for her careful review and improvement of the English language.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWang Q-P, Lai D-H, Zhu X-Q, Chen X-G, Lun Z-R. Human angiostrongyliasis. Lancet Infect Dis. 2008;8:621\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1473-3099(08)70229-9\u003c/span\u003e\u003cspan address=\"10.1016/S1473-3099(08)70229-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnsdell V, Kramer KJ, McMillan JK, Gosnell WL, Murphy GS, Meyer BC, et al. Guidelines for the diagnosis and treatment of neuroangiostrongyliasis: updated recommendations. Parasitology. 2021;148:227\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/S0031182020001262\u003c/span\u003e\u003cspan address=\"10.1017/S0031182020001262\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurck HC, Fox MT, Cowie RH. Paratenic hosts of Angiostrongylus cantonensis and their relation to human neuroangiostrongyliasis globally. One Health. 2022;15:100426. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.onehlt.2022.100426\u003c/span\u003e\u003cspan address=\"10.1016/j.onehlt.2022.100426\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowe K, Kaluna L, Lozano A, Torres Fischer B, Tagami Y, McHugh R et al. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. Knight M, editor. PLoS ONE. 2019;14: e0209813. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0209813\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0209813\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKliks MM, Palumbo NE. Eosinophilic meningitis beyond the Pacific Basin: The global dispersal of a peridomestic zoonosis caused by angiostrongylus cantonensis, the nematode lungworm of rats. Soc Sci Med. 1992;34:199\u0026ndash;212. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0277-9536(92)90097-A\u003c/span\u003e\u003cspan address=\"10.1016/0277-9536(92)90097-A\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCowie RH, Ansdell V, Panosian Dunavan C, Rollins RL, Neuroangiostrongyliasis. Global Spread of an Emerging Tropical Disease. Am J Trop Med Hyg. 2022;107:1166\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4269/ajtmh.22-0360\u003c/span\u003e\u003cspan address=\"10.4269/ajtmh.22-0360\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaume-Ramis S, Rivory P, Vel\u0026aacute;zquez IS, Šlapeta J, Paredes‐Esquivel C. Neuroangiostrongyliasis Infection Risk Near Preschool Centres in Mallorca, Spain: A Pilot Micro‐Epidemiological Study. Zoonoses Public Health. 2025;72:515\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/zph.13228\u003c/span\u003e\u003cspan address=\"10.1111/zph.13228\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePandian D, Šipkov\u0026aacute; A, Scarcelli S, Sgroi G, Kačmař\u0026iacute;kov\u0026aacute; J, Buono F, et al. Detection of Rat Lungworm (\u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e) in Rats and Gastropods, Italy. Emerg Infect Dis. 2025;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid3109.250648\u003c/span\u003e\u003cspan address=\"10.3201/eid3109.250648\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosen L, Loison G, Laigret J, Wallace GD. Studies on eosinophilic meningitis. 3. Epidemiologic and clinical observations on pacific islands and the possible etiologic role of Angiostrongylus cantonensis. Am J Epidemiol. 1967;85:17\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/oxfordjournals.aje.a120673\u003c/span\u003e\u003cspan address=\"10.1093/oxfordjournals.aje.a120673\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlicata JE. The incidence of angiostrongylus cantonensis among rats and mollusks in new caledonia and nearby islands and its possible relation withe meningitis eosinophilic.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelot B, Delvallez G, Gourinat A-C, Molko N, Goarant C, Ducrot Y-M et al. Eosinophilic meningitis in New Caledonia: The role of Angiostrongylus cantonensis? Schieffelin J, editor. PLoS ONE. 2021;16: e0254964. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0254964\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0254964\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsh LR. Observations on the role of mollusks and planarians in the transmission of Angiostrongylus cantonensis infection to man in new caledonia. Rev Biol Trop. 1976;24:163\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMora J-S. M\u0026eacute;ningite \u0026agrave; \u0026eacute;osinophiles \u0026agrave; Angiostrongylus cantonensis: investigation d\u0026rsquo;un cluster remarquable de 17 patients dans la tribu de Mucaweng, sur l\u0026rsquo;\u0026icirc;le de Lifou, en Nouvelle-Cal\u0026eacute;donie. Bordeaux. 2025. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://dumas.ccsd.cnrs.fr/dumas-05300150v1/file/Med_generale_2025_Mora.pdf\u003c/span\u003e\u003cspan address=\"https://dumas.ccsd.cnrs.fr/dumas-05300150v1/file/Med_generale_2025_Mora.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraeff-Teixeira C, Sawanyawisuth K, Lv S, Sears W, Rodr\u0026iacute;guez ZG, \u0026Aacute;lvarez HH, et al. Neuroangiostrongyliasis: Updated Provisional Guidelines for Diagnosis and Case Definitions. Pathogens. 2023;12:624. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/pathogens12040624\u003c/span\u003e\u003cspan address=\"10.3390/pathogens12040624\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEamsobhana P, Gan XX, Ma A, Wang Y, Wanachiwanawin D, Yong HS. Dot immunogold filtration assay (DIGFA) for the rapid detection of specific antibodies against the rat lungworm \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e (Nematoda: Metastrongyloidea) using purified 31-kDa antigen. J Helminthol. 2014;88:396\u0026ndash;401. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/S0022149X13000321\u003c/span\u003e\u003cspan address=\"10.1017/S0022149X13000321\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXue DY, Ruan YZ, Lin BC, Zheng RY, Fang JQ, Zhao QX, et al. [Epidemiological investigation on an outbreak of angiostrongyliasis cantonensis in Wenzhou]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2000;18:176\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlom TJ, Cortese MM, Gerber SI, Jones RC, Holtz TH, Lopez AS, et al. An Outbreak of Eosinophilic Meningitis Caused by \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e in Travelers Returning from the Caribbean. N Engl J Med. 2002;346:668\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa012462\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa012462\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai H-C, Lee SS-J, Huang C-K, Yen C-M, Chen E-R, Liu Y-C. Outbreak of eosinophilic meningitis associated with drinking raw vegetable juice in southern Taiwan. Am J Trop Med Hyg. 2004;71:222\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4269/ajtmh.2004.71.222\u003c/span\u003e\u003cspan address=\"10.4269/ajtmh.2004.71.222\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalvy D, Ezzedine K, Receveur M-C, Pistone T, Crevon L, Lemardeley P, et al. Cluster of eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in French policemen troop returning from the Pacific Islands. Travel Med Infect Dis. 2008;6:301\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.tmaid.2008.06.003\u003c/span\u003e\u003cspan address=\"10.1016/j.tmaid.2008.06.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin C-W, Liu Y-L, Lin HZ, Wang R-D, Wei S-T, Wu Y-C, et al. Cluster of Angiostrongylus cantonensis Infection in Tainan County, 2009. Epidemiol Bull. 2010;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.6525/TEB.201002_26(4).0003\u003c/span\u003e\u003cspan address=\"10.6525/TEB.201002_26(4).0003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang L, Darasavath C, Chang K, Vilay V, Sengduangphachanh A, Adsamouth A, et al. Cluster of Angiostrongyliasis Cases Following Consumption of Raw Monitor Lizard in the Lao People\u0026rsquo;s Democratic Republic and Review of the Literature. TropicalMed. 2021;6:107. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/tropicalmed6030107\u003c/span\u003e\u003cspan address=\"10.3390/tropicalmed6030107\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQvarnstrom Y, Bs HSB. Detection of Rat Lungworm in Intermediate, Definitive, and Paratenic Hosts Obtained from Environmental Sources. Public Health. 2013;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRollins RL, Medeiros MCI, Cowie RH. Stressed snails release Angiostrongylus cantonensis (rat lungworm) larvae in their slime. One Health. 2023;17:100658. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.onehlt.2023.100658\u003c/span\u003e\u003cspan address=\"10.1016/j.onehlt.2023.100658\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCowie RH. Pathways for Transmission of Angiostrongyliasis and the Risk of Disease Associated with Them. Public Health. 2013;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKramer KJ, Posner J, Gosnell WL. Role of Gastropod Mucus in the Transmission of \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e, a Potentially Serious Neurological Infection. ACS Chem Neurosci. 2018;9:629\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1021/acschemneuro.7b00491\u003c/span\u003e\u003cspan address=\"10.1021/acschemneuro.7b00491\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaisiri K, Dusitsittipon S, Panitvong N, Ketboonlue T, Nuamtanong S, Thaenkham U, et al. Distribution of the newly invasive New Guinea flatworm \u003cem\u003ePlatydemus manokwari\u003c/em\u003e (Platyhelminthes: Geoplanidae) in Thailand and its potential role as a paratenic host carrying \u003cem\u003eAngiostrongylus malaysiensis\u003c/em\u003e larvae. J Helminthol. 2019;93:711\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/S0022149X18000834\u003c/span\u003e\u003cspan address=\"10.1017/S0022149X18000834\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsato R, Taira K, Nakamura M, Kudaka J, Itokazu K, Kawanaka M. Changing Epidemiology of Angiostrongyliasis Cantonensis in Okinawa Prefecture, Japan. Jpn J Infect Dis. 2004;57:184\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7883/yoken.JJID.2004.184\u003c/span\u003e\u003cspan address=\"10.7883/yoken.JJID.2004.184\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProciv P, Spratt DM, Carlisle MS. Neuro-angiostrongyliasis: unresolved issues. Int J Parasitol. 2000;30:1295\u0026ndash;303. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0020-7519(00)00133-8\u003c/span\u003e\u003cspan address=\"10.1016/S0020-7519(00)00133-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJarvi SI, Eamsobhana P, Quarta S, Howe K, Jacquier S, Hanlon A, et al. Estimating Human Exposure to Rat Lungworm (Angiostrongylus cantonensis) on Hawai\u0026rsquo;i Island: A Pilot Study. Am J Trop Med Hyg. 2020;102:69\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4269/ajtmh.18-0242\u003c/span\u003e\u003cspan address=\"10.4269/ajtmh.18-0242\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"infectious-diseases-of-poverty","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"idop","sideBox":"Learn more about [Infectious Diseases of Poverty](http://idpjournal.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/idop/default.aspx","title":"Infectious Diseases of Poverty","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Eosinophilic meningitis, New Caledonia, Angiostrongylus cantonensis, Platydemus manokwari, angiostrongyliasis, outbreak investigation, emerging infectious disease","lastPublishedDoi":"10.21203/rs.3.rs-9272013/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9272013/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEosinophilic meningitis due to \u003cem\u003eAngiostrongylus cantonensis\u003c/em\u003e is an emerging parasitic disease worldwide, while remaining endemic in the Pacific region for several decades. In New Caledonia, a small number of sporadic cases occur each year, and the route of transmission is often unclear. In January 2023, an unusual cluster of three cases occurred in a small village following community festivities, leading to an epidemiological investigation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe conducted a retrospective epidemiological and environmental investigation approximately one month after the suspected exposure. Cases were defined according to international criteria and classified as confirmed, probable, or suspected. Clinical data were collected from medical records and interviews. Food exposures were reconstructed using participant interviews. Environmental observations focused on potential contamination sources in food preparation areas. Serological analyses were performed in symptomatic and asymptomatic exposed individuals.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNineteen cases were identified, including three confirmed and sixteen suspected cases. Among suspected cases, seven were classified as high suspicion, eight as moderate, and one as low suspicion. The most common symptom was headache (n\u0026thinsp;=\u0026thinsp;16), frequently associated with vomiting (n\u0026thinsp;=\u0026thinsp;9) or paresthesias (n\u0026thinsp;=\u0026thinsp;4). All cases attended festivities on December 27\u0026ndash;28, suggesting a common exposure period. The median incubation time was 3 weeks (IQR: 2\u0026ndash;4). Two main exposure hypotheses were identified: beverages diluted with rainwater and contamination of blended fruit juice prepared in an open-air kitchen. Environmental observations revealed rats and gastropods near food preparation areas, including on utensils left to dry outdoors. No parasite DNA was detected in water samples. Serological testing performed nine months later in ten exposed asymptomatic individuals was positive in all cases.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis investigation considers the possibility of waterborne transmission of \u003cem\u003eA. cantonensis\u003c/em\u003e, although the most plausible hypothesis is the accidental incorporation of a heavily infected gastropod into blended fruit juice during preparation, potentially facilitated by open-air kitchens in rural Pacific settings. It highlights the diagnostic and epidemiological challenges of this infection in endemic areas, where milder or nonspecific presentations may not lead to lumbar puncture. Serological testing may assist in case identification but remains limited by cross-reactivity and prior exposure.\u003c/p\u003e","manuscriptTitle":"Cluster of 19 Cases of Eosinophilic Meningitis due to Angiostrongylus cantonensis in Lifou, New Caledonia: An Outbreak Investigation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 12:28:40","doi":"10.21203/rs.3.rs-9272013/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"35984871807943155368414791400237654300","date":"2026-05-18T19:40:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-15T07:43:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152271314652138363132048586991605273676","date":"2026-05-01T01:08:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89571832293868474797033188573372865473","date":"2026-04-15T19:40:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332269646263569347894507826651583450050","date":"2026-04-10T03:20:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-10T02:10:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T02:07:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-09T16:36:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Infectious Diseases of Poverty","date":"2026-03-30T21:21:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"infectious-diseases-of-poverty","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"idop","sideBox":"Learn more about [Infectious Diseases of Poverty](http://idpjournal.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/idop/default.aspx","title":"Infectious Diseases of Poverty","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8366b700-5452-4063-b6d4-0d36a636d329","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"35984871807943155368414791400237654300","date":"2026-05-18T19:40:11+00:00","index":29,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-15T07:43:31+00:00","index":21,"fulltext":""},{"type":"reviewerAgreed","content":"152271314652138363132048586991605273676","date":"2026-05-01T01:08:29+00:00","index":20,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-19T12:28:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 12:28:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9272013","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9272013","identity":"rs-9272013","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}