Next Article in Journal
Challenges and Strategies for Developing Recombinant Vaccines against Leptospirosis: Role of Expression Platforms and Adjuvants in Achieving Protective Efficacy
Next Article in Special Issue
Barriers with Valve Mechanisms Are Predicted to Protect Crops from Slug Carriers of Rat Lungworm Disease
Previous Article in Journal
Comparison of Source Attribution Methodologies for Human Campylobacteriosis
Previous Article in Special Issue
Rapid Single-Step Immunochromatographic Assay for Angiostrongylus cantonensis Specific Antigen Detection
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Pathogens
Volume 12
Issue 6
10.3390/pathogens12060788
pathogens-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

The Global Spread Pattern of Rat Lungworm Based on Mitochondrial Genetics

by
Xia Tian
1,2,3,4,5,
Shen Chen
1,2,3,4,5,
Lei Duan
1,2,3,4,5,
Yingjun Qian
1,2,3,4,5,
Hongmei Li
1,2,3,4,5 and
Shan Lv
1,2,3,4,5,*
1
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, China
2
Key Laboratory on Parasite and Vector Biology, National Health Commission, Shanghai 200025, China
3
WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China
4
National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China
5
Chinese Center for Tropical Diseases Research, Shanghai 200025, China
*
Author to whom correspondence should be addressed.
Pathogens 2023, 12(6), 788; https://doi.org/10.3390/pathogens12060788
Submission received: 23 April 2023 / Revised: 15 May 2023 / Accepted: 29 May 2023 / Published: 31 May 2023
(This article belongs to the Special Issue Rat Lungworm Disease)
Browse Figures
Review Reports Versions Notes

Abstract

:
Eosinophilic meningitis due to rat lungworm, Angiostrongylus cantonensis, is a global public health concern. Human cases and outbreaks have occurred in the new endemic areas, including South America and Spain. The growing genetic data of A. cantonensis provides a unique opportunity to explore the global spread pattern of the parasite. Eight more mitochondrial (mt) genomes were sequenced by the present study. The phylogeny of A. cantonensis by Bayesian inference showed six clades (I–VI) determined by network analysis. A total of 554 mt genomes or fragments, which represented 1472 specimens of rat lungworms globally, were used in the present study. We characterized the gene types by mapping a variety of mt gene fragments to the known complete mt genomes. Six more clades (I2, II2, III2, V2, VII and VIII) were determined by network analysis in the phylogenies of cox1 and cytb genes. The global distribution of gene types was visualized. It was found that the haplotype diversity of A. cantonensis in Southeast and East Asia was significantly higher than that in other regions. The majority (78/81) of samples beyond Southeast and East Asia belongs to Clade II. The new world showed a higher diversity of Clade II in contrast with the Pacific. We speculate that rat lungworm was introduced from Southeast Asia rather than the Pacific. Therefore, systematic research should be conducted on rat lungworm at a global level in order to reveal the scenarios of spread.

1. Introduction

Angiostrongylus cantonensis is the major cause of human neural angiostrongyliasis [1]. Infection with this nematode often results in eosinophilic meningitis (EM) and other disorders of the central nervous system [2]. Humans are vulnerable to infection because of the varied contact opportunities with mollusk intermediate hosts and paratenic hosts. EM occurs following ingestion of undercooked or raw snails, slugs, freshwater shrimp or crabs, lizards, and even contaminated vegetable salad with mollusk slime [3].
A. cantonensis was first discovered from the pulmonary arteries and heart of rats in southern China in 1933 [4]. Human EM due to A. cantonensis was first reported in 1945 [5], followed by EM outbreaks in Pohnpei, of the Caroline Islands of the Pacific between 1947 and 1948 [6]. However, the health concern was not noted in the early 1960s when an outbreak occurred in Tahiti [7]. The subsequent surveys indicated that EM due to A. cantoensis was endemic in Southeast Asia and the Pacific [8]. Cases reported in recent years indicate that A. cantoensis constitutes an emerging zoonosis worldwide [9,10,11].
The expansion of the endemic range of A. cantonensis has been, to an extent, attributed to biological invasion. The common definitive host, the black rat Rattus rattus and the Norway rat R. norvegicus, are listed as the world’s top invasive species [12]. The growing shipping industry, particularly for cargo, drove the global spread of the two Rattus species and thus A. cantonensis. The intermediate host snail, Achatina fulica, was thought to play a key role in the spread of A. cantonensis in World War II, particularly in the Pacific islands [13]. Indeed, the land snail occupied the islands quickly in the 1940s and 1950s [14]; however, some human cases attributed to the consumption of A. fulica were reported earlier [15]. The snail has also recently begun to be considered an important factor in the occurrence of A. cantonensis in South America [16]. Another global invasive snail species is Pomacea canaliculata, which has been widely distributed in Southeast and East Asia since the 1980s [17]. The freshwater snail has driven the emergence of human neural angiostrongyliasis in the region [18]. The continuous invasion and re-introduction of definitive and intermediate hosts make the global spread of A. cantonensis more complex.
Rat lungworm commonly refers to A. cantonensis. However, rat lungworm also includes A. mackerrasae and A. malaysiensis, which were not distinguished from A. cantonensis until the late 1960s [19,20]. Although they have a nearly consistent life cycle, their geographical range and preference for a definitive host are different. In contrast with the global distribution of A. cantonensis, A. mackerrasae is confined to the east coast of Australia [21] and A. malaysiensis is mainly distributed in Thailand, Malaysia and Indonesia [19,22]. The most common definitive host of A. mackerrasae is the bush rat R. fuscipes and swamp rat Rattus lutreolus [21], while A. malaysiensis prefers the Malaysian field rat R. tiomanicus and the ricefield rat R. argentiventer [23]. Nevertheless, the two species have also been discovered from the global invasive R. norvegicus. Therefore, it is possible that the two species of Angiostrongylus may be distributed beyond the original regions. In addition, the diagnosis of most infections in human and animal was based on larval morphology and immunology, the infections due to A. mackerrasae and A. malaysiensis were probably misdiagnosed. For example, a recent report has shown through molecular evidence that A. malaysiensis can infect humans [24].
The genetic data of rat lungworms are increasingly prevalent around the world, providing an opportunity to reveal the global spread pattern of A. cantoensis and check the possibility of a range expansion for A. mackerrasae and A. malaysiensis. However, the molecular markers are diverse, with a focus on mitochondrial (mt) genes, including cytochrome c oxidase 1 gene (cox1) [25,26], cytochrome b gene (cytb) [27], NADH dehydrogenase 1 gene (nad1) [28], ribosomal subunit RNA gene [29], and even complete mt genomes [30]. In the present study, we will characterize the available complete mt genomes and map the known gene fragments to the mt genomes so that we can categorize the samples from multiple published works. Finally, the global distribution patterns of the gene types will be revealed and the global spread pattern of A. cantoensis will be inferred.

2. Materials and Methods

2.1. Mitochondrial Genomes

The present study will provide eight full mt genomes of A. cantonensis. The adult worms of A. cantonensis were collected from the pulmonary arteries of wild rats during the first national survey in China [31], or from Sprague–Dawley rats that were infected by third stage larvae from snails or slugs. Nine female worms from seven collecting sites were used for sequencing mt genomes (Table 1). One of the full sequences had been published (GQ398121). The other eight were characterized by the same methods and used for the present study [32]. In addition, the mt genomes of A. cantonensis, A. malaysiensis and A. mackerrasae that are deposited in GenBank were also included in the present analysis.

2.2. Mitochondrial Gene Sequences

Since our analysis strategy is to map the mt genes to the known complete mt genomes and then determine the types of each sequence, all mt gene sequences of A. cantonensis, A. malaysiensis and A. mackerrasae were collected from GenBank and used for the present study. Meanwhile, the collection information of specimens, e.g., location, year, species, gene name, sample size were also collected. For the sequences which had been published in papers but not yet submitted to GenBank, we collected the sequences directly from the papers including Supplementary Materials.

2.3. Phylogenetic Analysis

The complete mt genomes of A. cantonensis, A. malaysiensis and A. mackerrasae were used to construct phylogeny with the A. vasorum (JX268542) and A. costaricensis (GQ398122) as outgroups. A phylogenetic tree was constructed under Bayesian inference, performed in MrBayes version 3.2.7 [31]. Prior to Bayesian inference, the best fit nucleotide substitution model (GTR+G) for the dataset was determined using a hierarchical likelihood ratio test in jModeltest version 2 [32]. The posterior probabilities were calculated using Markov chain Monte Carlo (MCMC) simulations. At the end of this run, the average standard deviation of split frequencies was below 0.01, and the potential scale reduction factor was reasonably close to 1.0 for all parameters. A consensus tree was visualized and edited by Mesquite version 3.70 [36] or FigTree version 1.4.4 (http://tree.bio.ed.ac.uk/software/Figtree/; accessed on 28 May 2023).
The group of complete mt genomes was also submitted to network analysis by TCS version 1.21 [36]. Subgroups were determined with a connection limit of 1% or 132 steps and considered as the clades in the phylogenetic tree mentioned above.
The mt gene sequences downloaded from GenBank and papers were first categorized by the gene name. The sequences of the same gene were mapped to the complete mt genomes by alignment in clustal X. The sequences might be divided into subgroups when the overlapped length was less than 50%. After being trimmed as necessary, the grouped sequences were submitted to DnaSP version 5 [37] and the haplotypes were determined. The phylogenetic trees based on the haplotypes were inferred following the guide described above.
Some studies characterized the sequence of different mt genes of the same specimen, e.g., cox1 and cytb. Only one gene for a single specimen was taken into analysis. The gene cox1 was of priority because it was used broadly, followed by cytb and small ribosomal RNA gene. Large ribosomal RNA gene and nad1 were excluded because cox1 and small ribosomal RNA gene from the same specimens were included.
The gene fragments deduced from the 18 whole mt sequences of A. cantonensis, A. malaysiensis and A. malaysiensis were included as index markers in the individual gene phylogenetic trees. Each haplotype was assigned to a specific clade as delineated by whole mt genomes according to the index markers. New clades could be defined if the haplotypes in the clades were separated by network analysis with a connection limit of 1%, the same threshold as in analysis of full mt genomes. If a new clade was clustered with a specific known clade inferred according to the full mt genomes, the new clade would have the same name with a suffix of 2. Otherwise, a new name would be given to the new clade.

2.4. Mapping the Distribution Pattern

The coordinates of specimen collecting sites were either directly collected from the published papers or determined by Google Earth by inputting the location names which were extracted from the papers and GenBank. Each gene sequence from known locations was assigned to a specific clade determined in phylogenetic analysis.
The geographic distributions of gene types were mapped and visualized in a geographical information system (ArcGIS version 10.1). We merged some collecting sites for better display when the distance among them was less than 0.8 degrees at the global level and less than 0.5 degrees at the subregion level.

3. Results

A total of 18 mt genomes of rat lungworms were used in the analysis, including 10 from GenBank and 8 from the present study (Table 1, File S1). The genetic distance among three species of rat lungworm was around 0.12, while the genetic distance among various strains of A. cantonensis ranged from 0.001 to 0.056 (Table 2). The phylogenetic and network analyses showed that 15 mt genomes of A. cantonensis collapsed into six clades, encoded as clade I to clade VI (Figure 1). One genome (KT186242), previously identified as A. cantonensis, had closer genetic relation to A. malaysiensis (KT947979) according to the present study. Another genome (MN793157) belonged to A. mackerrasae.
The individual gene phylogenetic trees of cox1, nad1 and small ribosomal RNA genes from 18 complete mt genomes were re-constructed by Bayesian inference (File S2). When incorporated into the individual gene phylogenetic trees, the gene fragments deduced from the whole mt sequences all remained in their original clades, as expected.
A total of 554 mt genomes or fragments, which represented 1472 specimens of rat lungworms globally (Table 3), were used in the present study. The specimens were collected from 224 sites. According to our analysis one mt genome (KT186242), 13 cox1 sequences and 64 cytb sequences were A. malaysiensis and had previously been identified as A. cantonensis.
There are 327 cox1 sequences, including 160 fragments from GenBank, 18 mt genomes and 149 sequences from our previous study. One sequence (LC515249) was excluded due to the lack of overlap with any other sequence. The rest of the 326 sequences were divided into two subgroups according to the criteria of an overlap of less than 50%. The first subgroups included 308 sequences, which belonged to 112 haplotypes. All six of the clades (I ~ VI) based on the complete mt genomes were observed in the phylogenetic tree based on the first subgroups of cox1 genes. Meanwhile, another four clades were identified and named as Clade I-2, Clade II-2, Clade III-2 and Clade V-2 based on their relations to the six known clades (Figure 2). The second subgroup included 18 sequences, belonging to 11 haplotypes. All the sequences fell into Clade II (Figure 3).
Ten cytb sequences from the same specimens of cox1 were excluded in the analysis. The rest of the 195 cytb sequences, including 177 from GenBank and 18 from complete mt genomes, collapsed into 67 haplotypes. Eight clades were found in the phylogenetic analysis (Figure 4), including six that were determined according to complete mt genomes and two distinctive clades named Clade VII and VIII. The average genetic distance of sequences in Clade VIII to the other clades of A. cantonensis was over 5% (Table S1). The difference could be as high as 7%.
Twelve sequences of small and large ribosomal RNA genes were from the same specimens. Taking into consideration the smaller ribosomal subunit gene (ON747257), 13 small ribosomal RNA genes were used in the analysis. The sequences formed five haplotypes. According to network analysis, three haplotypes belonged to Clade II (Figure 5), while another two haplotypes fell into Clade I and III, respectively.
The gene types (clades) based on phylogenetic and network analyses were mapped in the world (Figure 6, Table S2). A much higher diversity of clades was observed in Southeast and East Asia. In contrast, almost all 81 specimens of A. cantonensis beyond the region belonged to Clade II, except for two (Clade IV) from Hawaii and one (Clade V) from Rio de Janeiro. In Asia, the Annamite range might be considered the genetic barrier for A. cantonensis (Figure 7). The gene types of Clade III, IV, V, V-2, VI and VIII were mainly distributed east of the Annamite range. On the contrary, Clade I, III-2 and VII were commonly found to the west of the Annamite range. A. malaysiensis was commonly found in in the west of Annamite range. However, it was also discovered in Taiwan according to the present analysis. A. mackerrasae was only observed in Australia.
The cox1 sequence types in Clade II were further categorized into ten subgroups (Figure 8). According to the geographic distribution of the subgroups, the haplotype diversity beyond Southeast and East Asia was 0.944, which was higher than that of 0.4641 in Asia (Figure 9). Clade II was not commonly observed in Asia according to available data. For example, Clade II was not discovered in the mainland of China and the northern part of the Greater Mekong subregion, though intensive sampling was undertaken and the high genetic diversity of A. cantonensis was observed in the region. Another feature of clade distribution in Asia was that none of the seven clades, except for Clade II-G, was simultaneously observed in two or more sites.
Clade II-G is the most common type, accounting for 48.57% of Clade II and found in seven sites in the world, five of which were located in the Pacific islands. Meanwhile the clade was also extended to the southeast shore area of Brazil. In contrast with the Pacific, the new world shows a higher diversity of clades, including the predominant clades II-D and II-E. Although the clade II-D1 and clade II-D3 were observed on Taiwan island and eastern Australia, 90% of the samples of Clade II-D were from the new world and Spain, while Australia shared two clades with Southeast Asia and South America.

4. Discussion

A total of 18 complete mt genomes of rat lungworms are currently available. Only one mt genome is A. mackerrasae and A. malaysiensis, respectively. The genetic distance among the species is over 0.11, while that among the different geographical strains within species is less than 0.06. Therefore, the species of rat lungworm could be definitively distinguished based on genetic distance. The genetic distance of the mt genome (KT186242), previously identified as A. cantonensis, was over 0.11 to any known strain of A. cantonensis. In contrast, the genome is almost identical to the mt genome (KT947979) diagnosed as A. malaysiensis. Therefore, KT186242 should be A. malaysiensis.
There were two hypotheses about the origin of A. cantonensis. Earlier opinion indicated that the parasite originated from Africa, which was supported by the fact that the discovery of A. cantonensis coincided with the spread of the African land snail A. fulica to Southeast Asia [38]. However, the theory of Asian origin later became popular. It was thought that the parasite was originally endemic to Southeast Asia and spread by the shipping rats, R. rattus and R. norvegicus, due to extensive traveling [13]. Our results show a much higher genetic diversity of A. cantonensis in Southeast and East Asia, supporting the latter theory.
Although intensive sampling occurred in China, Japan and the Great Mekong subregion, the common gene types (e.g., Clade II-D and Clade II-E shown in Figure 9) in America were rarely found in the region mentioned above. It was therefore believed that the gene types must be from anywhere else in Southeast Asia. Of note, Clade II was genetically close to Clade I. The latter was found only in Thailand and Myanmar, where A. malaysiensis co-occurred. The phenomenon of significant correlation between genetic and geographical distances is commonly observed in population genetics [39]. Therefore, Clade II was possibly from either Myanmar or the lower reach of the Mekong River. Similarly, Clade V showed longer genetic distance from any other clade within A. cantonensis, though the clade co-occurred with clade IV in China and Japan. We did not obtain any genetic evidence from the Philippines, but the country holds the potential to harbor the Clade V as a local gene type. A total of 124 cox1 samples from 24 collecting sites were available in Japan, and they consisted of 4 clades. However, the haplotype diversity of the samples was very low compared with Southeast Asia and the south of China [28,40]. Only seven haplotypes were identified, including three unique haplotypes within a single sample. Therefore, A. cantonensis in Japan might have been introduced from Southeast Asia and/or the south of China.
Our results show that there might be a genetic barrier between the Greater Mekong subregion and the south of China. The geographical isolation due to the Annamite range located in Vietnam may play a key role in the genetic divergence of A. cantonensis. Previous studies have indicated different evolutionary trajectories on western and eastern sides of the Annamite Mountain range [41]. The case of liver fluke also supports this opinion. Two species of liver fluke, i.e., Clonorchis sinensis and Opisthorchis viverrini, are widely distributed in the region. The former is distributed northeast of the Annamite range, while the latter is endemic in the southwest [42,43].
Clade II is the overwhelming gene type beyond Southeast and East Asia except for a small number of samples of Clade IV and Clade V in Hawaii and Rio de Janeiro, respectively. The conclusive global spread route of rat lungworm could not be established based on the present available genetic data. However, our findings imply that the gene types on the Pacific islands, where EM outbreaks occurred between the 1940s and 1960s, show identical and low diversity, which implies that its re-introduction after the Pacific War is less plausible [13]. Australia is the only country where A. cantonensis was reported earlier [21]. Our findings show there was no relation between Australia and the Pacific based on the available evidence, while the majority of samples are genetically close to those from Thailand. The new world, recently identified as endemic areas, probably showed a distinct haplotype structure from the Pacific and hence might have been directly introduced to the rat lungworm from Southeast Asia.
Compared with the global distribution of A. cantonensis, A. mackerrasae and A. malaysiensis are endemic locally. According to our results A. mackerrasae was only found on the eastern shore of Australia. Although A. mackerrasae was also discovered from R. norvegicus, it shows a higher susceptibility to local Australian rodents, e.g., R. fuscipes, R. lutreolus and Melomys cervinipes [21]. Therefore, A. mackerrasae was not endemic beyond the original region. A. malaysiensis showed a wider range of definitive hosts than A. mackerrasae. Although A. malaysiensis seems more susceptible to R. tiomanicus and R. argentiventer, the parasite shared 80% of definitive hosts with A. cantonensis, including the most invasive R. norvegicus and R. rattus (unpublished data). Our present study indicates that A. malaysiensis had gone beyond the original region and established local transmission in eastern Taiwan, since the worms had been isolated from the intermediate host A. fulica [44,45].
In order to reveal the complex spread pattern of A. cantonensis, we suggest the following research priorities. First, more mt genomes of rat lungworm should be characterized. Our present study identified new clades with complete mt genome sequences not yet available. Second, we need to fill the gap of genetic information in the Philippines and Indonesia, and even Myanmar. Since these countries are neighboring to the Greater Mekong subregion and East Asia, the mt genetic information of rat lungworms will be invaluable in constructing the phylogeny. Unfortunately, the large-scale survey has not been conducted and the mt genetic information has been lacking to date, though rat lungworms have been reported in the Philippines and Indonesia since the 1950s. Third, systemic sampling around the world is proposed to update either rare specimens or a small number of collecting sites beyond the Greater Mekong subregion and East Asia. In addition, the types of host animals, i.e., mollusks and rodents, were different in previous studies. It should be noted that the host preferences of species or strains of rat lungworm may cause a bias, and hence lead to false conclusions.

5. Conclusions

We showed an integrated global distribution of gene types by mapping various fragments to the known complete mt genomes. The new endemic areas including the new world and Spain showed different compositions of gene types to Southeast and East Asia and even the Pacific. Therefore, we need to conduct systematic research on rat lungworm at a global level in order to reveal the scenarios of spread.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pathogens12060788/s1, File S1: Eighteen mt genomes of rat lungworm used in the data analysis; File S2: Comparison between trees based on mt genomes and individual genes; Table S1: Difference matrix of cytb sequences; Table S2: Localities and gene types of samples.

Author Contributions

Conceptualization, S.L.; formal analysis, X.T. and S.L.; data collection and analysis, X.T., S.C. and L.D.; writing—original draft preparation, X.T.; writing—review and editing, Y.Q., H.L. and S.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by National Key Research and Development Program of China, grant numbers 2021YFC2300800, 2021YFC2300804; and the International Development Research Centre, grant number 108100-001.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The supporting data used in the study are available in the Supplementary Materials.

Acknowledgments

We would like to thank Shenning Lu from National Institute of Parasitic Diseases, China CDC for English editing.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Lv, S.; Zhang, Y.; Steinmann, P.; Zhou, X.N.; Utzinger, J. Helminth infections of the central nervous system occurring in Southeast Asia and the Far East. Adv. Parasitol. 2010, 72, 351–408. [Google Scholar] [PubMed]
  2. Wang, Q.P.; Lai, D.H.; Zhu, X.Q.; Chen, X.G.; Lun, Z.R. Human angiostrongyliasis. Lancet Infect. Dis. 2008, 8, 621–630. [Google Scholar] [CrossRef] [PubMed]
  3. Barratt, J.; Chan, D.; Sandaradura, I.; Malik, R.; Spielman, D.; Lee, R.; Marriott, D.; Harkness, J.; Ellis, J.; Stark, D. Angiostrongylus cantonensis: A review of its distribution, molecular biology and clinical significance as a human pathogen. Parasitology 2016, 143, 1087–1118. [Google Scholar] [CrossRef] [Green Version]
  4. Chen, H.T. A preliminary report on a survey of animal parasites of Canton, China, rats. Lingnan Sci. J. 1933, 12, 65–74. [Google Scholar]
  5. Nomura, S.; Lin, P.H. First case report of human infection with Haemostrongylus ratti Yokogawa. Taiwan No Ikai 1945, 3, 589–592. [Google Scholar]
  6. Bailey, C.A. An Epidemic of Eosinophilic Meningitis, a Previously Undescribed Disease, Occuring on Ponape, Eastern Carolines; Report No. 7; Naval Medical Research Institute, National Naval Medical Center: Bethesda, MD, USA, 1948; pp. 1–23. [Google Scholar]
  7. Rosen, L.; Laigret, J.; Bories, S. Observations on an outbreak of eosinophilic meningitis on Tahiti, French Polynesia. Am. J. Hyg. 1961, 74, 26–42. [Google Scholar]
  8. Alicata, J.E.; Jindrak, K. Angiostrongylosis in the Pacific and Southeast Asia; Thomas Publisher: Springfield, IL, USA, 1970; p. 105. [Google Scholar]
  9. Solorzano Alava, L.F.; Martini Robles, L.; Hernandez Alvarez, H.; Sarracent Perez, J.; Muzzio Aroca, J.; Rojas Rivero, L. Angiostrongylus cantonensis: An emerging parasite in Ecuador. Rev. Cub. Med. Trop. 2014, 66, 20–33. [Google Scholar]
  10. Foronda, P.; Lopez-Gonzalez, M.; Miquel, J.; Torres, J.; Segovia, M.; Abreu-Acosta, N.; Casanova, J.C.; Valladares, B.; Mas-Coma, S.; Bargues, M.D.; et al. Finding of Parastrongylus cantonensis (Chen, 1935) in Rattus rattus in Tenerife, Canary Islands (Spain). Acta Trop. 2010, 114, 123–127. [Google Scholar] [CrossRef] [PubMed]
  11. Garcia, M.H.; Moraes, C.; Almada, G.L.; Carvalho, O.S.; Caldeira, R.L.; Mendonça, C.L.; Zanon, D.M.; Antunes, F.A.; Santelli, A.C.; Castro, S.; et al. First reported outbreak of eosinophilic meningitis caused by Angiostrongylus cantonensis in Brazil. In Proceedings of the International Conference on Emerging Infectious Diseases, Atlanta, GA, USA, 16–19 March 2008; p. 59. [Google Scholar]
  12. Lowe, S.; Browne, M.; Boudjelas, S.; De Poorter, M. 100 of the World’s Worst Invasive Alien Species A selection from the Global Invasive Species Database; The Invasive Species Specialist Group (ISSG) a specialist group of the Species Survival Commission (SSC) of the World Conservation Union (IUCN): Auckland, New Zealand, 2000; p. 12. [Google Scholar]
  13. Kliks, M.M.; Palumbo, N.E. 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. [Google Scholar] [CrossRef]
  14. Mead, A.R. The Giant African Snail: A Problem in Economic Malacology; University of Chicago Press: Chicago, IL, USA, 1961; p. 257. [Google Scholar]
  15. Kliks, M.M.; Kroenke, K.; Hardman, J.M. Eosinophilic radiculomyeloencephalitis: An angiostrongyliasis outbreak in American Samoa related to ingestion of Achatina fulica snails. Am. J. Trop. Med. Hyg. 1982, 31, 1114–1122. [Google Scholar] [CrossRef]
  16. Graeff-Teixeira, C. Expansion of Achatina fulica in Brazil and potential increased risk for angiostrongyliasis. Trans. R. Soc. Trop. Med. Hyg. 2007, 101, 743–744. [Google Scholar] [CrossRef]
  17. Joshi, R.C.; Sebastian, L.S. Global Advances in Ecology and Management of Golden Apple Snails; PhilRice: Nueva Ecija, Philippines, 2006; p. 588. [Google Scholar]
  18. Lv, S.; Zhang, Y.; Steinmann, P.; Zhou, X.N. Emerging angiostrongyliasis in Mainland China. Emerg. Infect. Dis. 2008, 14, 161–164. [Google Scholar] [CrossRef] [PubMed]
  19. Bhaibulaya, M.; Cross, J.H. Angiostrongylus malaysiensis (Nematoda: Metastrongylidae), a new species of rat lung-worm from Malaysia. Southeast Asian J. Trop. Med. Public Health 1971, 2, 527–533. [Google Scholar] [PubMed]
  20. Bhaibulaya, M. A new species of Angiostrongylus in an Australian rat, Rattus fuscipes. Parasitology 1968, 58, 789–799. [Google Scholar] [CrossRef]
  21. Prociv, P.; Spratt, D.M.; Carlisle, M.S. Neuro-angiostrongyliasis: Unresolved issues. Int. J. Parasitol. 2000, 30, 1295–1303. [Google Scholar] [CrossRef]
  22. Stafford, E.E.; Tanudjaja, S.; Purnomo; Carney, W.P. Angiostrongylus malaysiensis in Indonesia. Southeast Asian J. Trop. Med. Public Health 1976, 7, 490–491. [Google Scholar]
  23. Lim, B.L.; Ramachandran, C.P. Ecological studies on Angiostrongylus malaysiensis (Nematoda: Metastrongylidae) in Malaysia. In Studies on Angiostrongyliasis in Southeast Asia and Australia; John, H.C., Ed.; U. S. Naval Medical Research Unit No. 2: Taipei, Taiwan, 1979; p. 164. [Google Scholar]
  24. Watthanakulpanich, D.; Jakkul, W.; Chanapromma, C.; Ketboonlue, T.; Dekumyoy, P.; Lv, Z.; Chan, A.H.E.; Thaenkham, U.; Chaisiri, K. Co-occurrence of Angiostrongylus malaysiensis and Angiostrongylus cantonensis DNA in cerebrospinal fluid: Evidence from human eosinophilic meningitis after ingestion of raw snail dish in Thailand. Food Waterborne Parasitol. 2021, 24, e00128. [Google Scholar] [CrossRef]
  25. Mallaiyaraj Mahalingam, J.T.; Calvani, N.E.D.; Lee, R.; Malik, R.; Šlapeta, J. Using cerebrospinal fluid to confirm Angiostrongylus cantonensis as the cause of canine neuroangiostrongyliasis in Australia where A. cantonensis and Angiostrongylus mackerrasae co-exist. Curr. Res. Parasitol. Vector Borne Dis. 2021, 1, 100033. [Google Scholar] [CrossRef]
  26. Valentyne, H.; Spratt, D.M.; Aghazadeh, M.; Jones, M.K.; Šlapeta, J. The mitochondrial genome of Angiostrongylus mackerrasae is distinct from A. cantonensis and A. malaysiensis. Parasitology 2020, 147, 681–688. [Google Scholar] [CrossRef]
  27. Dumidae, A.; Janthu, P.; Subkrasae, C.; Dekumyoy, P.; Thanwisai, A.; Vitta, A. Genetic characterization of Angiostrongylus larvae and their intermediate host, Achatina fulica, in Thailand. PLoS ONE 2019, 14, e0223257. [Google Scholar] [CrossRef]
  28. Lv, S.; Zhang, Y.; Steinmann, P.; Utzinger, J.; Zhou, X.N. The genetic variation of Angiostrongylus cantonensis in the People’s Republic of China. Infect. Dis. Poverty 2017, 6, 125. [Google Scholar] [CrossRef] [Green Version]
  29. Jhan, K.Y.; Cheng, C.J.; Jung, S.M.; Lai, Y.J.; Chen, K.Y.; Wang, L.C. Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with Angiostrongylus cantonensis: Histopathological and RNA-seq Analyses. Biomolecules 2021, 11, 536. [Google Scholar] [CrossRef]
  30. Červená, B.; Modrý, D.; Fecková, B.; Hrazdilová, K.; Foronda, P.; Alonso, A.M.; Lee, R.; Walker, J.; Niebuhr, C.N.; Malik, R.; et al. Low diversity of Angiostrongylus cantonensis complete mitochondrial DNA sequences from Australia, Hawaii, French Polynesia and the Canary Islands revealed using whole genome next-generation sequencing. Parasit Vectors 2019, 12, 241. [Google Scholar] [CrossRef] [Green Version]
  31. Lv, S.; Zhang, Y.; Liu, H.X.; Hu, L.; Yang, K.; Steinmann, P.; Chen, Z.; Wang, L.Y.; Utzinger, J.; Zhou, X.N. Invasive snails and an emerging infectious disease: Results from the first national survey on Angiostrongylus cantonensis in China. PLoS Negl. Trop. Dis. 2009, 3, e368. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Lv, S.; Zhang, Y.; Zhang, L.; Liu, Q.; Liu, H.X.; Hu, L.; Wei, F.R.; Steinmann, P.; Graeff-Teixeira, C.; Zhou, X.N.; et al. The complete mitochondrial genome of the rodent intra-arterial nematodes Angiostrongylus cantonensis and Angiostrongylus costaricensis. Parasitol. Res. 2012, 111, 115–123. [Google Scholar] [CrossRef] [Green Version]
  33. Yong, H.S.; Song, S.L.; Eamsobhana, P.; Lim, P.E. Complete mitochondrial genome of Angiostrongylus malaysiensis lungworm and molecular phylogeny of Metastrongyloid nematodes. Acta Trop. 2016, 161, 33–40. [Google Scholar] [CrossRef]
  34. Yong, H.S.; Song, S.L.; Eamsobhana, P.; Goh, S.Y.; Lim, P.E. Complete mitochondrial genome reveals genetic diversity of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae). Acta Trop. 2015, 152, 157–164. [Google Scholar] [CrossRef] [PubMed]
  35. Gasser, R.B.; Jabbar, A.; Mohandas, N.; Schnyder, M.; Deplazes, P.; Littlewood, D.T.; Jex, A.R. Mitochondrial genome of Angiostrongylus vasorum: Comparison with congeners and implications for studying the population genetics and epidemiology of this parasite. Infect. Genet. Evol. 2012, 12, 1884–1891. [Google Scholar] [CrossRef]
  36. Clement, M.; Posada, D.; Crandall, K.A. TCS: A computer program to estimate gene genealogies. Mol. Ecol. 2000, 9, 1657–1659. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Librado, P.; Rozas, J. DnaSP v5: A software for comprehensive analysis of DNA polymorphism data. Bioinformatics 2009, 25, 1451–1452. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  38. Alicata, J.E. The presence of Angiostrongylus cantonensis in islands of the Indian Ocean and probable role of the giant African snail, Achatina fulica, in dispersal of the parasite to the Pacific Islands. Can. J. Zool. 1966, 44, 1041–1049. [Google Scholar] [CrossRef] [PubMed]
  39. Ramachandran, S.; Deshpande, O.; Roseman, C.C.; Rosenberg, N.A.; Feldman, M.W.; Cavalli-Sforza, L.L. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc. Natl. Acad. Sci. USA 2005, 102, 15942–15947. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  40. Eamsobhana, P.; Song, S.L.; Yong, H.S.; Prasartvit, A.; Boonyong, S.; Tungtrongchitr, A. Cytochrome c oxidase subunit I haplotype diversity of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae). Acta Trop. 2017, 171, 141–145. [Google Scholar] [CrossRef] [PubMed]
  41. Bain, R.H.; Hurley, M.M. A biogeographic synthesis of the amphibians and reptiles of Indochina. Bull. Am. Mus. Nat. Hist. 2011, 360, 1–138. [Google Scholar] [CrossRef]
  42. Qian, M.B.; Chen, Y.D.; Liang, S.; Yang, G.J.; Zhou, X.N. The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma. Infect. Dis. Poverty 2012, 1, 4. [Google Scholar] [CrossRef] [Green Version]
  43. IARC. A review of human carcinogens. In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; World Health Organization: Geneva, Switzerland, 2012; Volume 100B, p. 441. [Google Scholar]
  44. Lee, J.D.; Chung, L.Y.; Wang, L.C.; Lin, R.J.; Wang, J.J.; Tu, H.P.; Wu, Z.D.; Yen, C.M. Sequence analysis in partial genes of five isolates of Angiostrongylus cantonensis from Taiwan and biological comparison in infectivity and pathogenicity between two strains. Acta Trop. 2014, 133, 26–34. [Google Scholar] [CrossRef]
  45. Peng, J.; He, Z.P.; Zhang, S.; Lun, Z.R.; Wu, Z.D.; Fan, C.K.; Brown, C.L.; Cheng, P.C.; Peng, S.Y.; Yang, T.B. Phylogeography of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) in southern China and some surrounding areas. PLoS Negl. Trop. Dis. 2017, 11, e0005776. [Google Scholar] [CrossRef] [Green Version]
Pathogens 12 00788 g001 550
Figure 1. The phylogeny of rat lungworm inferred from mitochondrial genomes, with A. vasorum (JX268542) and A. costaricensis (GQ398122) as outgroups.
Figure 1. The phylogeny of rat lungworm inferred from mitochondrial genomes, with A. vasorum (JX268542) and A. costaricensis (GQ398122) as outgroups.
Pathogens 12 00788 g001
Pathogens 12 00788 g002 550
Figure 2. The phylogeny of rat lungworm inferred via the first group of cox1 haplotypes. The cox1 fragments of eighteen available full mitochondrial genomes are included as index of clades. The code and branch color is consistent with Figure 1. Four new clades, i.e., Clade I-2, Clade II-2, Clade III-2, and Clade V-2, are identified based on the network analysis.
Figure 2. The phylogeny of rat lungworm inferred via the first group of cox1 haplotypes. The cox1 fragments of eighteen available full mitochondrial genomes are included as index of clades. The code and branch color is consistent with Figure 1. Four new clades, i.e., Clade I-2, Clade II-2, Clade III-2, and Clade V-2, are identified based on the network analysis.
Pathogens 12 00788 g002
Pathogens 12 00788 g003 550
Figure 3. The phylogeny of rat lungworm inferred via the second group of cox1 haplotypes. The gene sequences used in this phylogeny showed <50% overlap with the sequences used in Figure 2.
Figure 3. The phylogeny of rat lungworm inferred via the second group of cox1 haplotypes. The gene sequences used in this phylogeny showed <50% overlap with the sequences used in Figure 2.
Pathogens 12 00788 g003
Pathogens 12 00788 g004 550
Figure 4. The phylogeny of rat lungworm inferred via the cytb haplotypes. Two new clades, i.e., Clade VII and Clade VIII, were identified in the phylogeny compared with Figure 1.
Figure 4. The phylogeny of rat lungworm inferred via the cytb haplotypes. Two new clades, i.e., Clade VII and Clade VIII, were identified in the phylogeny compared with Figure 1.
Pathogens 12 00788 g004
Pathogens 12 00788 g005 550
Figure 5. The phylogeny of rat lungworm inferred via the mitochondrial small ribosomal RNA gene.
Figure 5. The phylogeny of rat lungworm inferred via the mitochondrial small ribosomal RNA gene.
Pathogens 12 00788 g005
Pathogens 12 00788 g006 550
Figure 6. The global distribution of gene types of rat lungworm. The sites with a distance less than 0.8 degrees were combined and displayed at the geometric center. Amal: A. malaysiensis, Amac: A. mackerrasae.
Figure 6. The global distribution of gene types of rat lungworm. The sites with a distance less than 0.8 degrees were combined and displayed at the geometric center. Amal: A. malaysiensis, Amac: A. mackerrasae.
Pathogens 12 00788 g006
Pathogens 12 00788 g007 550
Figure 7. The distribution of gene types of rat lungworm in Southeast and East Asia. The sites with a distance of less than 0.5 degrees were combined and displayed at the geometric center. Amal: A. malaysiensis, Amac: A. mackerrasae.
Figure 7. The distribution of gene types of rat lungworm in Southeast and East Asia. The sites with a distance of less than 0.5 degrees were combined and displayed at the geometric center. Amal: A. malaysiensis, Amac: A. mackerrasae.
Pathogens 12 00788 g007
Pathogens 12 00788 g008 550
Figure 8. The phylogenetic relation of Clade II (cox1) subgroups.
Figure 8. The phylogenetic relation of Clade II (cox1) subgroups.
Pathogens 12 00788 g008
Pathogens 12 00788 g009 550
Figure 9. The global distribution of Clade II (cox1) with sample size. Grey dot indicate the distribution of other clades.
Figure 9. The global distribution of Clade II (cox1) with sample size. Grey dot indicate the distribution of other clades.
Pathogens 12 00788 g009
Table
Table 1. The mitochondrial genomes of Angiostrongylus used in phylogenetic analysis.
Table 1. The mitochondrial genomes of Angiostrongylus used in phylogenetic analysis.
SpeciesAccess NumberLocationAltitudeLongitudeReferences
A. cantonensisAP017672Taipei, China25.0329121.5655[30]
CL_AcanChangle, China25.9313119.6288this study
DF1_AcanDongfang, China19.0535108.6521this study
DF2_AcanDongfang, China19.0535108.6521this study
GQ398121Lianjiang, China26.2052119.5212[32]
KT947978Thailand [26]
MK570629Tenerife, Spain28.2916−16.6291[30]
MK570630Hawaii, USA19.6310−156.0072[30]
MK570631Mosman, Australia−33.8293151.2442[30]
MK570632Fatu Hiva, French Polynesia−17.6427−149.4347[30]
NA_AcanNanao, China23.4533117.0971this study
RL_AcanRuili, China23.947797.7854this study
SC_AcanShangchuan, China21.6613112.8016this study
SY_AcanSanya, China18.3333109.4333this study
ZX_AcanZixing, China26.0365113.2463this study
A. mackerrasaeMN793157Brisbane, Australia−27.4620153.0203[33]
A. malaysiensisKT186242Thailand [34]
KT947979Kuala Lumpur, Malaysia3.1201101.6545[26]
A. vasorumJX268542Australia [35]
A. costaricensisGQ398122Brazil [32]
Table
Table 2. Genetic distance based on complete mitochondrial genomes.
Table 2. Genetic distance based on complete mitochondrial genomes.
MN793157KT186242KT947979CL_AcanNA_AcanGQ398121SY_AcanZX_AcanMK570632MK570630MK570629AP017672MK570631KT947978RL_AcanDF1_AcanDF2_Acan
KT1862420.133
KT9479790.1330.002
CL_Acan0.1160.1240.124
NA_Acan0.1160.1250.1240.001
GQ3981210.1170.1250.1250.0020.002
SY_Acan0.1150.1230.1230.0080.0070.009
ZX_Acan0.1160.1230.1230.0150.0150.0160.014
MK5706320.1180.1250.1250.0350.0350.0360.0340.034
MK5706300.1180.1240.1240.0340.0340.0350.0330.0330.001
MK5706290.1180.1230.1230.0340.0340.0350.0330.0340.0110.010
AP0176720.1180.1230.1230.0340.0340.0350.0330.0340.0110.0100.001
MK5706310.1180.1230.1230.0340.0340.0350.0330.0330.0110.0100.0010.001
KT9479780.1180.1240.1240.0340.0340.0350.0330.0330.0180.0170.0160.0160.016
RL_Acan0.1190.1250.1250.0340.0340.0350.0330.0330.0190.0190.0170.0170.0170.009
DF1_Acan0.1180.1240.1240.0350.0350.0360.0330.0340.0300.0290.0290.0290.0290.0290.030
DF2_Acan0.1170.1240.1240.0350.0350.0360.0330.0340.0300.0290.0290.0290.0290.0280.0300.001
SC_Acan0.1170.1260.1260.0510.0520.0520.0510.0530.0560.0560.0550.0560.0550.0550.0550.0560.056
Table
Table 3. Mitochondrial gene sequences used in the present study.
Table 3. Mitochondrial gene sequences used in the present study.
TypesA. cantonensisA. mackerrasaeA. malaysiensisTotal
mt genome8 (16 *)1 (1)1 (1)10 (18)
cox1144 (426 #)5 (5)11 (23)160 (454)
cytb177 (655 $)0 (0)76 (76)253 (731)
nad10 (130)0 (0)0 (0)0 (130)
SSU13 (13)0 (0)53 (53)66 (66)
LSU12 (12)0 (0)53 (53)65 (65)
Total354 (1252)6 (6)194 (206)554 (1472)
Note: the figures inside and outside brackets represent the number of sequences from GenBank and the number of samples, respectively. SSU: small ribosomal RNAS gene; LSU: large ribosomal RNAS gene. * including 8 genomes from the present study and one genome (KT186242) of A. malaysiensis mistaken for A. cantonensis. # including 13 sequences of A. malaysiensis mistaken for A. cantonensis $ including 64 sequences of A. malaysiensis mistaken for A. cantonensis.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Tian, X.; Chen, S.; Duan, L.; Qian, Y.; Li, H.; Lv, S. The Global Spread Pattern of Rat Lungworm Based on Mitochondrial Genetics. Pathogens 2023, 12, 788. https://doi.org/10.3390/pathogens12060788

AMA Style

Tian X, Chen S, Duan L, Qian Y, Li H, Lv S. The Global Spread Pattern of Rat Lungworm Based on Mitochondrial Genetics. Pathogens. 2023; 12(6):788. https://doi.org/10.3390/pathogens12060788

Chicago/Turabian Style

Tian, Xia, Shen Chen, Lei Duan, Yingjun Qian, Hongmei Li, and Shan Lv. 2023. "The Global Spread Pattern of Rat Lungworm Based on Mitochondrial Genetics" Pathogens 12, no. 6: 788. https://doi.org/10.3390/pathogens12060788

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop