Epidemiology of Angiostrongylus cantonensis and eosinophilic meningitis in the People's Republic of China

Lv, Shan. Epidemiology of Angiostrongylus cantonensis and eosinophilic meningitis in the People's Republic of China. 2011, PhD Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_9790


Background: Human eosinophilic meningitis is mainly caused by the rat lungworm Angiostrongylus cantonensis, especially in tropical and subtropical regions. Since the mid-1940s, more than 2800 cases of eosinophilic meningitis have been reported in at least 30 countries. Of note, A. cantonensis is one of a few helminths that can cause an outbreak within a short time period (usually within 2 weeks). Fatal cases, particular among young children, have been reported in heavily infected subjects. Eosinophilic meningitis is paradoxically an emerging infectious disease in the People¡¯s Republic of China (P.R. China). Indeed, while the rat lungworm was discovered in Guangzhou (formerly Canton) in 1933, there were only few cases reported until the mid 1990s. However, the biological invasion of two exotic snail species, namely the African land snail Achatina fulica and the South American freshwater snail Pomacea spp., drove the emergence of this disease. Thus far, more than three-quarter of human cases could definitely be related to the consumption of these snail species, particularly Pomacea spp. The seven outbreaks that occurred between 1997 and 2006 in P.R. China were all attributed to these two invasive snail species.
Due to the emergence of eosinophilic meningitis and the issue of outbreaks that occurred at a growing frequency in P.R. China, there as a felt need to deepen our understanding of the epidemiology and control of this disease. Although several small-scale surveys pertaining to A. cantonensis had been carried out in P.R. China, the exact distribution of the parasite, and the invasive snail species that act as intermediate hosts remained to be determined.
Goal and objectives: The overarching goal of this thesis is to improve our knowledge on the epidemiology of A. cantonensis and eosinophilic meningitis in P.R. China. There are six specific and interlinked objectives: (i) to identify the control priorities in eosinophilic meningitis by observing and analyzing outbreaks; (ii) to reveal the geographical distribution of A. cantonensis and to identify the major intermediate hosts; (iii) to characterize the mitochondrial (mt) genome of A. cantonensis and its close relative A. costaricensis in order to identify genetic marker that might give rise to novel diagnostic assays and population genetic studies; (iv) to evaluate the intraspecific differentiation of A. cantonensis and explore the potential dynamic scenarios in P.R. China; (v), to assess the genetic diversity of the invasive snail species Pomacea spp. and explore potential spread scenarios; and (vi) to assess the interplay between invasive snails, climate change and transmission dynamics.
Methodology and principal findings: In 2008, we had the opportunity to study an outbreak of angiostrongyliasis that occurred in Dali due to the consumption of Pomacea spp. We found a prolonged period (8 months) of this outbreak with the peak occurring in February 2008, owing to a traditional festival. Only 11 out of 33 patients with complete data records were categorized into clinically diagnosed cases, whereas the others were grouped into suspected cases according to the existing diagnosis criteria. None of the patients was parasitologically diagnosed. Some important information for diagnosis was missing, which reflected the ignorance of clinicians on this disease. The existing diagnosis criteria for clinically diagnosed case requested an elevated eosinophil count both in peripheral blood and in cerebrospinal fluid (CSF), which was rather restrict. Interestingly, not all patients simultaneously experienced a marked change in eosinophil count, both in peripheral blood and CSF. Our findings called for further standardization of diagnosis and generalization of the clinical criteria. Surveillance system in endemic areas should be established for both security of snail food and human cases in hospitals.
We had access to data obtained from the first national survey pertaining to A. cantonensis which was implemented using a geographical grid sampling approach. Our results showed that the rat lungworm was endemic in 59 of the 164 surveyed counties (36.0%), which represented seven south provinces in the mainland of P.R. China. Two of these provinces were newly confirmed. Two invasive snail species were identified as the key intermediate hosts. On average, the prevalence of A. cantonensis among A. fulica and Pomacea spp. was 13.4% and 6.8%, respectively. The prevalence among other terrestrial mollusks range from 0.3% (snail) to 6.5% (slugs), while that among freshwater snails was only 0.05%. Pomacea snails were found in 11 provinces, whereas A. fulica was encountered in six provinces.
The complete mt genomes of A. cantonensis and A. costaricensis are 13,497 bp and 13,585 bp in length, respectively. Hence, these two closely related nematodes have the smallest mt genomes in the class of Chromadorea characterized thus far. Overall nucleotide identity of these two mt genomes was 81.6%, with a range from 77.7% to 87.1% in individual gene pairs. These findings provide a sound basis for screening potential genetic markers for diagnosis and further in-depth population genetic studies. The mt genome-wide analysis identified three major gene arrangement patterns from 48 nematode mt genomes. The gene arrangement, coupled with a phylogenetic tree based on concatenated amino acid sequence, supported a closer relationship between Ascaridida and Strongylida rather than Spirurida, which is inconsistent with findings of previous studies according to the nuclear small ribosomal subunit DNA.
A. cantonensis specimens obtained from 33 collection sites were used to study the intraspecific differentiation based on the mitochondrial nad1 gene. A total of 73 haplotypes of A. cantonensis were identified from 143 sequences, which resulted in seven distinctive clades (Mainland, Hainan, Sanya, Tiane, Nanao, Zixing and Thailand). Geographical distance and natural isolation played a role in the spatial distribution of these clades, which supported the Southeast Asian origin from a molecular point of view. A considerable haplotype invasion was noted, which indicated the impact of human activities on biodiversity. The potential invasion routes for the clades Hainan, Sanya and Tiane were inferred based on a network analysis. The conflict between the presumptive origin of the clades Hainan and Tiane and those of the clades Nanao and Sanya call for further research.
A total of 523 sequences of mt gene cox1 of Pomacea spp. were obtained from 56 collection sites. Twenty-five haplotypes were identified with an overall diversity of 0.702, which was higher than those observed in previous studies. From a global point of view, only five out of 98 haplotypes, which were determined by the currently 228 available sequences in GenBank as well as the 523 sequences described in the present thesis, were shared between introduced (Southeast Asia) and native (South America) ranges. The 98 haplotypes were clustered into 10 groups. Six groups occurred in the mainland of P.R. China, among only two can be traced back to the South Americas, whereas were two also occurred in other countries in Southeast Asia. The remaining two groups only occurred in P.R. China. A phylogenetic analysis showed that two species (i.e. P. canaliculata and P. insularum) coexist in the mainland of P.R. China, although the phylogenetic position of group B is still pending. The definite spread route of this snail species was not determined, but the increased diversity in single collection sites indicated multiple and secondary introductions.
Finally, we developed a biology-driven model to determined potential impacts of climate change on the distribution of Pomacea spp., and hence the transmission of A. cantonensis. Mean January temperature and snail generation intensity (generation number) were identified as key factors determining the distribution of Pomacea spp.. The model predicted an increase of 56.9% for the ¡®spread¡¯ and a decrease of 40.9% for the ¡®establishment¡¯ regions (¡®spread¡¯ and ¡®establishment¡¯ defined according to the aforementioned national sampling survey) by the 2030s relative to the present day. Key determinants of A. cantonensis transmission were identified as the generation intensity in the intermediate host, the longevity of A. cantonensis-infected rats and the dormant period of Pomacea spp. Importantly, transmission of A. cantonensis occurs only in areas where the snail¡¯s dormant period is below 173.2 days. The potential endemic area of A. cantonensis was predicted to double by the 2030s relative to the present day.
Conclusions/significance: Outbreaks of eosinophilic meningitis are of particular and growing concern in P.R. China. Standardization and generalization of diagnosis and treatment are therefore urgently required to be better equipped for future outbreaks. The first national survey deepened our understanding of the distribution of A. cantonensis and two invasive snail species that have been identified as the key intermediate hosts. Our in-depth population genetic studies of A. cantonensis revealed that human activities changed the original distribution and might have facilitated long-distance dispersal. The well divergent clades implied that the mt genes are promising candidates for novel diagnostic markers and population genetic studies. Our research also showed that two species of Pomacea coexist in P.R. China. The current distribution indicated multiple and secondary introductions. Although the definite role of these snail in the current distribution pattern of A. cantonensis is not clear, the potential impact is considerable in a future warmer P.R. China.
Advisors:Utzinger, Jürg
Committee Members:Deplazes, Peter and Zhou, Xiao-Nong and Steinmann, Peter
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Eco System Health Sciences > Health Impact Assessment (Utzinger)
Item Type:Thesis
Thesis no:9790
Bibsysno:Link to catalogue
Number of Pages:210 S.
Identification Number:
Last Modified:30 Jun 2016 10:48
Deposited On:03 Apr 2012 06:57

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