Paragonimiasis.

Paragonimiasis is a zoonotic disease caused by lung flukes of the genus Paragonimus. Humans usually become infected by eating freshwater crabs or crayfish containing encysted metacercariae of these worms. However, an alternative route of infection exists: ingestion of raw meat from a mammalian paratenic host. Adult worms normally occur in pairs in cysts in the lungs from which they void their eggs via air passages. The pulmonary form is typical in cases of human infection due to P. westermani, P. heterotremus, and a few other species. Worms may occupy other sites in the body, notably the brain, but lung flukes have made their presence felt in almost every organ. Ectopic paragonimiasis is particularly common when infection is due to members of the P. skrjabini complex. Human paragonimiasis occurs primarily in the tropics and subtropics of Asia, Africa, and the Americas, with different species being responsible in different areas (Table 6.1).

Mitogenomic and nuclear ribosomal transcription unit datasets support the synonymy of Paragonimus iloktsuenensis and P. ohirai (Paragonimidae: Platyhelminthes).

The complete mitogenome (mtDNA) of nominal Paragonimus iloktsuenensis (Paragonimidae: Trematoda) and the nuclear ribosomal transcription unit (rTU) coding region (rTU*: from 5'-terminus of 18S to 3'-terminus of 28S rRNA gene, excluding the external spacer region) of this species and of P. ohirai were obtained and used to further support the previously suggested synonymy of these taxa in the P. ohirai complex. The complete mitogenome of P. iloktsuenensis was 14,827 bp long (GenBank: ON961029) and nearly identical to that of P. ohirai (14,818 bp; KX765277), with a 99.12% nucleotide identity. The rTU* was 7543 bp and 6932 bp in these two taxa, respectively. All genes and spacers in the rTU were identical in length, with exception of the first internal transcribed spacer, which contained multiple tandem repeat units (6.7 for P. iloktsuenensis and 5.7 for P. ohirai). There was near 100% identity for the rTU genes. The phylogenetic topology inferred from the mtDNA and from individual gene regions (partial cox1 of 387 bp and the ITS-2 of 282 bp - 285 bp) indicated a very close relationship consistent with synonymy of P. iloktsuenensis and P. ohirai. The datasets provided here will be useful for taxonomic reappraisal as well as studies of evolutionary and population genetics of the genus Paragonimus and family Paragonimidae.

A Cluster of Paragonimiasis with Delayed Diagnosis Due to Difficulty Distinguishing Symptoms from Post-COVID-19 Respiratory Symptoms: A Report of Five Cases.

Paragonimiasis caused by trematodes belonging to the genus Paragonimus is often accompanied by chronic respiratory symptoms such as cough, the accumulation of sputum, hemoptysis, and chest pain. Prolonged symptoms, including respiratory symptoms, after coronavirus disease 2019 infection (COVID-19) are collectively called post-COVID-19 conditions. Paragonimiasis and COVID-19 may cause similar respiratory symptoms. We encountered five cases of paragonimiasis in patients in Japan for whom diagnoses were delayed due to the initial characterization of the respiratory symptoms as a post-COVID-19 condition. The patients had consumed homemade drunken freshwater crabs together. One to three weeks after consuming the crabs, four of the five patients were diagnosed with probable COVID-19. The major symptoms reported included cough, dyspnea, and chest pain. The major imaging findings were pleural effusion, pneumothorax, and nodular lesions of the lung. All the patients were diagnosed with paragonimiasis based on a serum antibody test and peripheral blood eosinophilia (560-15,610 cells/µL) and were treated successfully with 75 mg/kg/day praziquantel for 3 days. Before diagnosing a post-COVID-19 condition, it is necessary to consider whether other diseases, including paragonimiasis, may explain the symptoms. Further, chest radiographic or blood tests should be performed in patients with persistent respiratory symptoms after being infected with COVID-19 to avoid overlooking the possibility of infection.

Pulmonary Paragonimiasis in Native Community, Esmeraldas Province, Ecuador, 2022.

Paragonimiasis is a food-borne infection caused by several species of the Paragonimus fluke. Clinical manifestations can mimic tuberculosis and contribute to diagnostic delay. We report a cluster of paragonimiasis in a community in Ecuador, where active surveillance was set up after detection of the first 2 cases.

A clinical review of human disease due to Paragonimus kellicotti in North America.

Human autochthonous infections with the trematode Paragonimus kellicotti are increasingly being reported in North America, but the true prevalence and geographic distribution are unknown. Ingestion of raw crayfish is reported in most human cases, typically in the context of alcohol intoxication. Risk of infection varies depending on what part of the crayfish is ingested as metacercariae of P. kellicotti (>50% mature to adults) localize to the heart and pericardium of the crayfish. Reported human cases have manifested primarily in otherwise healthy young adults presenting with severe eosinophilic pneumonia, pleuritis, systemic symptoms, dermatologic lesions and cerebral involvement. However, it is likely that many infections go unreported due to lack of awareness, mild illness or the absence of rapid commercially available diagnostic tests. Promising advances have been made related to novel diagnostic targets. Conservation of these antigen targets among at least four Paragonimus species could make these antigens viable for diagnostic testing of P. kellicotti specifically as well as other Paragonimus species, but additional studies and funding investments are required. Public and physician awareness may have improved due to targeted education campaigns, but ongoing activities to raise awareness are needed, particularly in areas where cases have not been frequently reported to date.

The complete mitogenome of the Asian lung fluke Paragonimus skrjabini miyazakii and its implications for the family Paragonimidae (Trematoda: Platyhelminthes).

The complete circular mitogenome of Paragonimus skrjabini miyazakii (Platyhelminthes: Paragonimidae) from Japan, obtained by PacBio long-read sequencing, was 17 591 bp and contained 12 protein-coding genes (PCGs), 2 mitoribosomal RNA and 22 transfer RNA genes. The atp8 gene was absent, and there was a 40 bp overlap between nad4L and nad4. The long non-coding region (4.3 kb) included distinct types of long and short repeat units. The pattern of base usage for PCGs and the mtDNA coding region overall in Asian and American Paragonimus species (P. s. miyazakii, P. heterotremus, P. ohirai and P. kellicotti) and the Indian form of P. westermani was T > G > A > C. On the other hand, East-Asian P. westermani used T > G > C > A. Five Asian and American Paragonimus species and P. westermani had TTT/Phe, TTG/Leu and GTT/Val as the most frequently used codons, whereas the least-used codons were different in each species and between regional forms of P. westermani. The phylogenetic tree reconstructed from a concatenated alignment of amino acids of 12 PCGs from 36 strains/26 species/5 families of trematodes confirmed that the Paragonimidae is monophyletic, with 100% nodal support. Paragonimus skrjabini miyazakii was resolved as a sister to P. heterotremus. The P. westermani clade was clearly separate from remaining congeners. The latter clade was comprised of 2 subclades, one of the East-Asian and the other of the Indian Type 1 samples. Additional mitogenomes in the Paragonimidae are needed for genomic characterization and are useful for diagnostics, identification and genetic/ phylogenetic/ epidemiological/ evolutionary studies of the Paragonimidae.

Lung flukes of the genus Paragonimus: ancient and re-emerging pathogens.

The title of this article refers to Table 1 in Zhou (2022, Infectious diseases of poverty: progress achieved during the decade gone and perspectives for the future. Infectious Diseases of Poverty 11, 1), in which it is indicated that Paragonimus species, like many other foodborne trematodes, are ancient pathogens that are also re-emerging to cause disease in modern times. This article provides a general overview of Paragonimus species and the disease they cause. This is followed by comments on several specific topics of current interest: taxonomy and distribution of members of the genus; details of the life cycle; global and regional prevalence of paragonimiasis; genomics of lung flukes and possible effects of global environmental change. Unresolved questions relating to these topics are discussed and gaps in knowledge identified.

Foodborne trematodes: old foes, new kids on the block and research perspectives for control and understanding host-parasite interactions.

Foodborne trematodes (FBTs) have a worldwide distribution (with particular prevalence in south-east Asia) and are believed to infect almost 75 million people, with millions more living at risk of infection. Although mortality due to trematodiasis is low, these infections cause considerable morbidity and some species are associated with the development of cancer in hyperendemic regions. Despite this, FBTs are often side-lined in terms of research funding and have been dubbed neglected tropical diseases by the World Health Organisation. Thus, the aim of this special issue was to provide an update of our understanding of FBT infections, to shine a light on current work in the field and to highlight some research priorities for the future. With contributions from leading researchers, many from endemic regions, we review the major FBT species. In doing so we revisit some old foes, uncover emerging infections and discover how outbreaks are being dealt with as a result of new approaches to parasite control. We also report advances in our understanding of the interactions of FBTs with their mammalian hosts and uncover new interplay between trematodes and host microbiome components. We hope that this article collection will stimulate discussion and further research on the FBTs and help raise them from their neglected status.

A case of cerebral paragonimiasis misdiagnosed as eosinophilic granulomatosis with polyangiitis.

Paragonimiasis is a parasitic disease caused by Paragonimus westermani infection, and migration to the brain results in cerebral paragonimiasis. Cerebral paragonimiasis is now extremely rare, but a few cases are still reported. A 48-year-old Japanese woman presented with right-hand convulsion, right-hand numbness, sputum, and fatigue. Chest computed tomography demonstrated multiple nodular lesions, and head computed tomography revealed a hemorrhagic lesion in the left motor cortex. Magnetic resonance imaging revealed multiple small ring-shaped lesions with surrounding edema. Laboratory evaluation demonstrated peripheral eosinophilia. We considered eosinophilic granulomatosis with polyangiitis and started steroid treatment as a diagnostic therapy since we wanted to avoid cerebral lesion biopsy if possible. However, the patient underwent craniotomy surgery after steroid treatment for four months because a new intracerebral mass lesion had appeared. Trematode eggs were detected in the sample, and the final diagnosis was cerebral paragonimiasis. The patient was successfully treated with praziquantel. Cerebral paragonimiasis is extremely rare but should be considered in the differential diagnosis if atypical intracranial hemorrhage and peripheral eosinophilia are observed.

A curious case of hemoptysis.

Paragonimiasis is a crustacean-borne parasitic zoonosis caused by lung fluke or Paragonimus. Several endemic foci of paragonimiasis have been discovered in Northeastern India. Chronic pulmonary infection with Paragonimus is characterized by hemoptysis, which is usually mistaken for Tuberculosis (TB). Paragonimiasis is acquired by eating raw, undercooked, or pickled crabs or crayfish containing encysted metacercariae of Paragonimus. Infection can usually be confirmed by finding Paragonimus eggs in sputum or bronchoalveolar lavage. We present a rare case of paragonimiasis masquerading as hypereosinophilia, asthma, and intracerebral hemorrhage for the last three years. Paragonimiasis is a rare cause of hemoptysis outside endemic regions. A strong index of suspicion is required to diagnose paragonimiasis outside the endemic areas. Diagnosis is usually delayed because of similarity of presentation to TB. Our patient was symptomatic with hemoptysis for three years. He gave history of eating raw crayfish and crabs while on leave to his native village in Nagaland. Diagnosis was confirmed on microscopy by detection of Paragonimus ova in sputum and bronchoalveolar lavage specimens. Symptoms resolved on treatment with praziquantel (25 mg/kg TDS for three days). Patient became symptom-free after a week of treatment.

Dynamic transcriptome landscape of Paragonimus proliferus developmental stages in the rat lungs.

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

Characterization and localization of antigens for serodiagnosis of human paragonimiasis.

Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the genomes of Paragonimus westermani, Paragonimus heterotremus, and Paragonimus miyazakii. Immunohistology studies showed that antibodies raised to four recombinant proteins bound to the tegument of adult P. kellicotti worms, at the parasite host interface. Only a known egg antigen was absent from the tegument but present in developing and mature eggs. We evaluated the diagnostic potential of these antigens by Western blot with sera from patients with paragonimiasis (from MO and the Philippines), fascioliasis, and schistosomiasis, and with sera from healthy North American controls. Two recombinant proteins (a cysteine protease and a myoglobin) showed the highest sensitivity and specificity as diagnostic antigens, and they detected antibodies in sera from paragonimiasis patients with early or mature infections. In contrast, antibodies to egg yolk ferritin appeared to be specific marker for patients with adult fluke infections that produce eggs. Our study has identified and localized antigens that are promising for serodiagnosis of human paragonimiasis.

Paragonimus heterotremus Chen et Hsia, 1964 (Digenea: Paragonimidae): species identification based on the biological and genetic criteria, and pathology of infection.

As a result of the experimental infection of rats with metacercariae of Paragonimus heterotremus Chen et Hsia, 1964 from crabs (Potamiscus tannanti) caught in Yen Bai province, Vietnam, it was found that worms migrated into the lungs, to the liver and less frequently to the tissue that lines body cavities of the hosts, where they reached the adult stage, but in the muscles, worms stayed at the larval stage. Studies have shown that for P. heterotremus, rats can simultaneously play the role of the final and paratenic host; herewith, an infection with the trematode of this species can lead to the development of three forms of paragonimiasis: pulmonary, hepatic and muscular. Eggs from the adult worms localised in the liver, unlike eggs from the adult worms localised in the lungs, were not excreted into the external environment, but accumulated inside the organ. Histology and description of changes, which take place on the external surface of organs affected with P. heterotremus, are given in this study. Based on the behavioural characteristics of worms during rat infection and molecular genetic data, we established that worms from Vietnam and India should be assigned to different species of Paragonimus. P. heterotremus distribution is limited to the territory of the Southeast China, Northern Vietnam, Laos and Thailand.

Asymptomatic Human Paragonimiasis among the Karen People in Tak Province, Thailand: A Case Report.

During the mobile clinic activities in Tak Province, Thailand, Paragonimus sp. eggs were found in a fecal sample of a 72-year-old Karen resident. Paragonimus DNA was amplified from the stool sample and identified to P. heterotremus. The patient did not have any symptoms. Apparent pulmonary lesion was not found on the chest X-ray. The patient admitted habitual consumption of semi-cooked or roasted waterfall crabs for several years. The waterfall crabs collected from stream near the village were found negative for Paragonimus metacercariae. In northern Thailand, paragonimiasis remains as one of the public health concerns and should be ruled out for asymptomatic pulmonary patients.

Differentially Expressed Homologous Genes Reveal Interspecies Differences of Paragonimus Proliferus based on Transcriptome Analysis.

Paragonimus proliferus (P. proliferus), one of 46 Paragonimus species registered in the National Center for Biotechnology Information database, may be much more widely distributed in Southeast Asia than previously thought, as its reported natural foci have increased in the past decades. However, very little is known about its molecular biology, especially at the transcriptome level. For the first time, the transcriptome of this species was sequenced and compared with four other common Paragonimus species, namely Paragonimus skrjabini, Paragonimus kellicotti, Paragonimus miyazakii, and Paragonimus westermani, to predict homologous genes and differentially expressed homologous genes to explore interspecies differences of Paragonimus proliferus. A total of 7393 genes were found to be significantly differentially expressed. Of these, 49 were considered to be core genes because they were differentially expressed in all four comparison groups. Annotations revealed that these genes were related mainly to "duplication, transcription, or translation", energy or nutrient metabolism, and parasitic growth, proliferation, motility, invasion, adaptation to the host, or virulence. Interestingly, a majority (5601/7393) of the identified genes, and in particular the core genes (48/49), were expressed at lower levels in P. proliferus. The identified genes may play essential roles in the biological differences between Paragonimus species. This work provides fundamental background information for further research into the molecular biology of P. proliferus.

Paragonimus westermani infection manifesting as a pulmonary cavity and adrenal gland mass: A case report.

We report a case of Paragonimus westermani infection simultaneously affecting two separate organs that presented as both a pulmonary cavity and adrenal mass in an immunocompromised host. A 65-year-old male with a previous kidney transplant visited our clinic because of hemoptysis. Chest computed tomography (CT) showed a pulmonary cavity and right adrenal gland mass. The Aspergillus antigen titer in bronchial lavage fluid was elevated and showed positive conversion. It was necessary to differentiate lung cancer with adrenal gland metastasis from a fungal infection with an adrenal gland adenoma. Positron emission tomography CT suggested benign disease, and it was misdiagnosed as pulmonary aspergillosis based on the elevated Aspergillus antigen titer in the bronchial lavage fluid. Owing to the adverse effects of anti-fungal treatment, the patient underwent wedge resection of the lung and P. westermani was confirmed. A careful history revealed that the patient had eaten raw freshwater crabs 3 years earlier, and a test for serum antibodies to P. westermani was positive. Despite treatment with praziquantel, the adrenal mass persisted on 3-month follow-up CT. A right adrenalectomy was performed and a P. westermani infection was confirmed.

Reconsideration of Dr. Allen's Report about Hemoptysis Patients from High Prevalence of Archaeoparasitological Paragonimiasis in Korea.

Horace N. Allen, an American physician, was a Presbyterian missionary to Korea. In 1886, he wrote the annual report of the Korean government hospital, summarizing patient statistics according to outpatient and inpatient classification for the first ever in Korean history. In the report, he speculated that hemoptysis cases of outpatient might have been mainly caused by distoma. Allen's conjecture was noteworthy because only a few years lapsed since the first scientific report of paragonimiasis. However, he was not sure of his assumption either because it was not evidently supported by proper microscopic or post-mortem examinations. In this letter, we thus revisit his assumption with our parasitological data recently obtained from Joseon period mummies.