Abstract
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KEYWORDS: Paragonimus spp., Ecuador, Paragonimus westermani, ceviche, Paragonimus kellicotti, Paragonimus mexicanus, raw fish
ANSWER TO PHOTO QUIZ
The structures were subsequently identified as eggs of Paragonimus spp. In lung tissue, asymmetric structures with a size of 84 µm (range from 80 µm to 120 µm) and yellow-brownish color are characteristic features of Paragonimus spp. eggs (1). Moreover, these structures had an elongated shape and a thick shell with a flattened end. In addition, at the larger end, the distinctive operculum was clearly visible, and the abopercular end was thickened (2). These eggs are unembryonated in the sputum or alternatively are swallowed, and excreted in the feces. There are more than 30 Paragonimus species but only 10 have been reported to infect humans. P. westermani and P. heterotremus are the most common species reported in human paragonimiasis, called “the oriental lung fluke,” followed by P. kellicotti (3). The genus level identification and diagnosis of Paragonimus spp. are established by microscopy. However, these eggs are indistinguishable between Paragonimus species, and molecular techniques are required for species level identification. The adult trematode specimens are ovoid with a size of approximately 1 cm and are located only in the lungs.
Several parasites should be included in the differential diagnosis of pulmonary helminthiases. The Ascaris lumbricoides third-stage filariform larvae (L3) could migrate to the lungs, after ingestion of infective eggs and subsequent invasion of the intestinal mucosa. A. lumbricoides larvae mature further in the lungs, penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed. However, A. lumbricoides eggs have a size of 45–90 µm, are rounded, found only in feces, and they have a thick shell with a mammillary outer layer (4). Hydatid disease caused by Echinococcus spp. results in hydatid cysts in the liver and lung. However, Echinococcus spp. eggs are only present in definitive animal hosts and are not found in humans (5). Strongyloides spp. third-stage filariform (L3) larvae penetrate the skin and may migrate through the bloodstream and lymphatic system before coughing up and swallowing. Strongyloides spp. larvae are more likely to be recovered from the lungs, however, in cases of disseminated disease and hyperinfection. Ancylostoma spp. and Necator americanus filariform larvae L3 also penetrate the skin and are transported through the blood vessels to the heart, and then to the lungs. However, Strongyloides spp., Ancylostoma spp., and Necator americanus eggs are only found in feces, as well as Ascaris spp., but not in lung tissue (5). Pulmonary dirofilariasis caused by Dirofilaria immitis occurs when an infected mosquito introduces L3 larvae into the skin when taking a blood meal. In humans, these L3 larvae or possible L4 larvae can die in the small pulmonary arteries and cause infarcts (6). Therefore, the presence of characteristic operculated eggs (80–120 µm long) in sputum, feces, or lung tissue suggests Paragonimus spp. infection.
Paragonimiasis is distributed throughout the Americas, Africa, and Southeast Asia. P. westermani and P. heterotremus are located in Southeast Asia and Japan. However, P. kellicotti is endemic to North America. Otherwise, P. kellicotti and P. mexicanus extend to Central and South America. However, although the molecular analysis was not performed, P. mexicanus is one of the most frequent species in Ecuador (7, 8).
The parasite cycle begins when the embryonated egg hatches and miracidium penetrates the soft tissues of the snail (first intermediate host). In snails, miracidia are transformed into sporocyst, rediae, and cercariae. The cercariae penetrate crustaceans such as a freshwater crab or crayfish (second intermediate host) and are transformed into metacercariae. This is the infective specimen for humans. Paragonimiasis infection is caused by the ingestion of pickled or inadequately cooked freshwater crustaceans with these metacercariae. We hypothesized that the patient could have been infected by ingesting a homemade ceviche when she traveled to Jipijapa, Ecuador. The patient reported that this recipe could have been prepared by her family using freshwater crab or crayfish. Some freshwater crustaceans (second intermediate host) have been reported in Ecuador, such as members of the genus Hypolobocera spp. (9).
After the consumption, metacercariae from the duodenum penetrate through the intestinal wall into the peritoneal cavity, and through the abdominal wall and diaphragm into the lung tissue in approximately 1 week. In the lungs, metacercariae become encapsulated and develop into adult specimens in approximately 5–6 weeks. Manifestations depend on the duration and probably the intensity of paragonimiasis infection (10). During the chronic stage, when adult specimens reside in the lungs and produce eggs, chronic cough is frequent (10).
The diagnosis is based on the microscopic demonstration of eggs mainly in feces or sputum. The eggs are expectorated and either expelled or swallowed, and passed in the feces. The time from infection to the oviposition and the presence of eggs in stool or sputum is around 65–90 days (1). However, Paragonimus spp. eggs were not found in the stool or sputum samples of our patient. The presence of eggs in the effusion fluid or biopsy material, as in this case, is uncommon. Moreover, these eggs can be calcified in lung tissue over time as in our case (11). However, the paragonimiasis infection can persist for 20 years in humans without symptoms (2, 3). Serological testing could be useful for confirming the diagnosis of paragonimiasis and monitoring the treatment. The immunoblot assay for P. westermani presents high sensitivity and specificity (10, 12). However, this serological test is mainly used by the Centers for Disease Control and Prevention.
The patient was treated with praziquantel 75 mg/kg/day administered in three doses for 2 days based on recommendations from observational studies and expert opinion with positive response to pharmacological treatment (2).
Paragonimiasis is a food-borne trematodiasis considered by the World Health Organization to be one of the most neglected tropical diseases, with pulmonary paragonimiasis being the most frequent presentation (7). There are other manifestations, such as cerebral or hepatic paragonimiasis, but they are less prevalent (13, 14). Ecuador reported the highest prevalence of human paragonimiasis in America in 2011, and it is considered a public health problem. Moreover, the second intermediate hosts have been reported in the providence of Jipijapa (8, 9). Between 1978 and 2007, the annual incidence was 85.5 cases per 100,000 population in 19 out of 24 provinces of Ecuador, with an estimated risk of infection of around 17.2% of the population (7).
ACKNOWLEDGMENTS
To my best friend, Sol San José Villar, for writing this Photo Quiz together during her DTM&H diploma at the London School of Hygiene & Tropical Medicine and my metagenomics fellow programme at Guy's and St Thomas' Hospital NHS Foundation Trust (HR57, London, UK).
Contributor Information
Alfredo Maldonado-Barrueco, Email: alfredo.maldonado@salud.madrid.org.
Bobbi S. Pritt, Mayo Clinic Minnesota, Rochester, Minnesota, USA
REFERENCES
- 1. Centers for Disease Control and Prevention . 2023. DPDx - Laboratory Identification of Parasites of Public Health Concern. Available from: https://www.cdc.gov/dpdx/paragonimiasis/index.html
- 2. Procop GW. 2009. North American paragonimiasis (caused by Paragonimus kellicotti) in the context of global paragonimiasis. Clin Microbiol Rev 22:415–446. doi: 10.1128/CMR.00005-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Blair D. 2019. Paragonimiasis, p 105–138. In Toledo R, Fried B (ed), Digenetic Trematodes. Springer International Publishing, Cham. [Google Scholar]
- 4. Wang J, Davis RE. 2020. Ascaris. Curr Biol 30:R423–R425. doi: 10.1016/j.cub.2020.02.064 [DOI] [PubMed] [Google Scholar]
- 5. Jourdan PM, Lamberton PHL, Fenwick A, Addiss DG. 2018. Soil-transmitted helminth infections. Lancet 391:252–265. doi: 10.1016/S0140-6736(17)31930-X [DOI] [PubMed] [Google Scholar]
- 6. Miterpáková M, Antolová D, Rampalová J, Undesser M, Krajčovič T, Víchová B. 2022. Dirofilaria immitis pulmonary. Emerging Infect. Dis 28. doi: 10.3201/eid2802.211963 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Calvopiña M, Romero D, Castañeda B, Hashiguchi Y, Sugiyama H. 2014. Current status of Paragonimus and paragonimiasis in Ecuador. Mem Inst Oswaldo Cruz 109:849–855. doi: 10.1590/0074-0276140042 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Iwagami M, Monroy C, Rosas MA, Pinto MR, Guevara AG, Vieira JC, Agatsuma Y, Agatsuma T. 2003. A molecular phylogeographic study based on DNA sequences from individual metacercariae of Paragonimus mexicanus from Guatemala and Ecuador. J Helminthol 77:33–38. doi: 10.1079/JOH2002147 [DOI] [PubMed] [Google Scholar]
- 9. Calvopina M, Romero-Alvarez D, Rendon M, Takagi H, Sugiyama H. 2018. Hypolobocera guayaquilensis (Decapoda: Pseudothelphusidae): a new crab intermediate host of Paragonimus mexicanus in Manabí province, Ecuador. Korean J Parasitol 56:189–194. doi: 10.3347/kjp.2018.56.2.189 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Zarrin-Khameh N, Citron DR, Stager CE, Laucirica R. 2008. Pulmonary paragonimiasis diagnosed by fine-needle aspiration biopsy. J Clin Microbiol 46:2137–2140. doi: 10.1128/JCM.02424-07 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Travis WD, Koss ML. 2002. Non-neoplastic disorders of the lower respiratory tract, American registry of pathology and armed forces Institute of pathology. American Registry of Pathology and Armed Forces Institute of Pathology, Bethesda, MD. [Google Scholar]
- 12. Narain K, Devi KR, Mahanta J. 2005. Development of enzyme-linked immunosorbent assay for serodiagnosis of human paragonimiasis. INDIAN J MED RES 121:739–746. [PubMed] [Google Scholar]
- 13. Moon SW, Kim T. 2022. Cerebral paragonimiasis presenting with dementia. Korean J Parasitol 60:353–355. doi: 10.3347/kjp.2022.60.5.353 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Gong Z, Xu Z, Lei C, Wan C. 2017. Hepatic paragonimiasis in a 15-month-old girl: a case report. BMC Pediatr 17:190. doi: 10.1186/s12887-017-0942-5 [DOI] [PMC free article] [PubMed] [Google Scholar]