Clinical Features and Treatment of Lung Fluke in Human - Research Paper Example

Lung Fluke in Human Detailed Outline Introduction a. What is lung fluke human disease? b. Cause. c. Effects Objective What is the purpose of this research? Methodology How this research will be conducted? What would be the keywords? What would be the sources of this study? Findings from the Literature Review Endemicity a. Causative agent b. Transmission c. Primary and secondary hosts d. Geographical distribution Diagnosis Definitive pathological diagnosis History Clinical findings Clinical pathological findings Clinical Features a. Pulmonary pathology b. Symptomatic presentation c. Radiologic diagnosis d. Immunological diagnosis e. Pathophysiologic links to diagnostic measures Radiologic Findings X-ray Explanation of x-ray findings Pathophysiologic Mechanism Inflammation Extrusion of the ova Tissue responses Clinical correlation Treatment Praziquantel Triclobendazole Tolerability Efficacy Conclusion Introduction Human lung fluke disease is being reported increasingly from different parts of the world. This has emerged as an important parasitic zoonosis. This disease is caused by Paragonimus westermani and P. miyazakii. This has been recognized to be representative parasitic infestations of human lungs from consumption of undercooked or raw secondary hosts harboring the parasites. The knowledge about this potentially preventable public health problem is limited due to paucity of focused research and laxity in reporting the data. Therefore research in this area is necessary in order to add to the knowledge and possibly devising preventive measures. Human lung fluke disease is characterized by cough and hemoptysis. The ova of Paragonimus westermani is expectorated in the sputum. The symptoms of this disease are surprisingly sparse. The other methods of clinical investigations such as physical examination and x-ray chest also prove to be negative in the clinical situations. The breath sounds which are often abnormal in any condition with lung parenchymal involvement are usually normal, although some degree of hyper-resonance may be detected on percussion. The hematologic parameters are essentially normal with moderate degree of leukocytosis or varying degree of anemia. Clinically or pathologically there are no indirect parameters which can be the hallmark of this disease. Therefore, the only diagnostic sign would be detection of the ova of Paragonimus westermani in the sputum. This is an endemic disease of public health importance in different geographical locations, but the clinical diagnostic parameters are hardly useful. Research in this area has been considerably less; consequently, there would be prominent gap in the knowledge about the human form of the disease. In this study, all available literature has been reviewed in order to update the knowledge, which could be clinically useful. Objective In this literature review different aspects of the disease of human lung fluke will be investigated from original research articles. The knowledge about this potentially preventable public health problem is limited due to paucity of focused research and laxity in reporting the data. Therefore research in this area is necessary in order to add to the knowledge and possibly devising preventive measures. Methodology In order to review the relevant literature, based on the objective cited, certain key words will be developed. The prospective key words would be “lung fluke,” “endemic hemoptysis”, “case reports”, “clinical features”, epidemiology”, “endemicity”, and “Paragonimus westermani and P. miyazakii”, “prevention”, “diagnosis”, and “treatment.” With the use of Boolean parameters these key words will be used to locate original research articles. From the University Library the articles published in the past 10 years were located which gave 445 results. Unfortunately, after exclusion of duplicate articles, out of 223 literatures, “human lung fluke” provided only 10 studies which were decided to be reviewed. Findings from Literature Review Clinical studies were only 2 in number. Therefore, the review will be arranged in the form of epidemiology, description of the parasite and intermediate host, lifecycle of the parasite in intermediate and human host, human behaviors predisposing to the zoonosis, clinical features, pathophysiology, laboratory and clinical diagnosis, the management, prevention, and global severity of the problem. There were no single study located which could deal separately with any of these aspects of the problem. Therefore, it was decided that to build a complete knowledge base relevant material and information from several studies will be taken as constructs in each of these areas. Special attention will be paid to the literatures dealing with the clinical features of this parasitic infestation. Endemicity Park et al. (2001) have indicated that Paragonimus westermani is considered to be the most significant causative agent of Asian paragonimiasis. The usual route of transmission is eating raw or undercooked crab or crayfish. The later usually serve as the second intermediate host. There have been 43 species of Paragonimus identified worldwide with geographical prevalence of certain species. Very commonly, snails are the first intermediate hosts, and the second intermediate hosts are crabs and Cray fish. In the Asian countries, snails are common, and human are one of the final hosts, the others being dogs, cats, and some other wild animals. DeFrain et al. (2002) in their study on North American Paragonimiasis reports that it is a disease of global distribution with multispecies causation, and worldwide it causes pulmonary disease. Culturally determined food preparations are the major method of the transmission of this disease in the Asian endemic region (DeFrain et al., 2002). Where endemicity is low, however, it is a rare cause of pulmonary disease. As indicated earlier and as highlighted in reports of Choo et al. (2003), Paragonimis westermani is the commonest of these problems and is common in Far East in countries such as Korea, China, Japan, and Tiwan. This is also called oriental lung fluke. In pathogenesis of the pulmonary disease, the lifecycle of this parasite is an important parameter to study. The ingestion of raw or insufficiently cooked second intermediate hosts of this parasite transmits the encysted metacercarcial stage. This passes into the small intestine and excyst there, penetrate the intestinal wall and are shed into the abdominal cavity. Followed by this, they migrate through the viscera and diaphragm ultimately to lodge into the lungs. It is here that the flukes develop which migrate within the lungs and has fair chances of migrating into the other organs (Choo et al., 2003). Singh et al. (2009) has reported similar findings from India. This disease has remained neglected as a public health problem in that country. Many cases have been reported in that country, and endemic foci have been recognized in different parts of the country. In contrast to the previous belief that P. westermani is the principal cause of human infestation, now in India, P. heterotremus has been recognized to be the principal cause of pulmonary disease caused by the parasite. Many cases are misdiagnosed as pulmonary tuberculosis and subsequently are parasitologically confirmed to be pulmonary paragonimiasis. These authors present a methodology of identifying these patients. A detailed clinical history regarding the food habits and other parameters of the development of the symptoms and physical examination are very important. A well intended sputum examination is the only way to identify the cases definitively (Singh et al., 2009). Diagnosis Jarilla et al. (2009) have indicated that the sputum samples should be collected in sterile containers which are screw capped. The microscopic examination would involve preservation of the sample in two parts, one portion in equal volume of 10% phosphate-buffered formalin for morphological study and another equal volume of 70% ethanol in order to characterize them. More direct evidence for the diagnosis of the study can be accomplished by microenzyme-linked immunosorbant assay (Jarilla et al. 2009). As early as in 1982, Johnson et al. reported cases on oriental lung fluke and its possible spread in the United States through Laotian refugees. In these Hmong migrants cases were reported where the affected individuals were traced to a refugee camp outbreak on the banks of the Mekong river in Thailand. Many of these patients presented with cough, hemoptysis, and fever beginning in the first three months of the illness. Some patients were reported to have dyspnea, pleurisy, and weight loss (Johnson et al., 1982). From their case reports and also as indicated in Mizuki et al. (1992), the clinical features of this disease can be reconstructed. The patients presenting with hemoptysis would also demonstrate infiltrates in the posteroanterior chest films, although in some cases there could be isolated pleural processes on x-ray examination. Mild anemia would be common with elevated white cell counts in most occasions with invariable eosinophilia in almost all affected individuals. It is very difficult to comment whether this eosinophilia was solely due to paragnomiasis since may patients would have associated other intestinal parasites. Sputum positive patients with paragnomiasis would be eosinophlic even following treatment of intestinal parasitosis (Mizuki et al. 1992). Clinical Features Jeon et al. (2005) studied the clinical features of recently diagnosed pulmonary paragonimiasis. They have also supported the pathway of this infestation as indicated earlier, that is, through ingestion of metacercarial stages and during transit through the pleural cavity from their adobe in the intestine, they have chances to seed the infection into the pleural cavity and then finally inside the pulmonary parenchyma, where the metacercariae would mature into adult flukes (Jeon et al., 2005). This has been supported by Yamazaki et al. (2008) in their case report of pulmonary paragonimiasis reported the incidence of encapsulated eosinophlic pleural effusion associated with peripheral blood eosinophilia. This finding was later correlated with a positive ELISA for Paragnomiasis-specific IgG antibodies. The presentation of this patient was atypical with a right sided pleural effusion. In the course of discussion on this patient, the authors have indicated a set of findings which may be encountered in CT scan of the pulmonary parenchyma in this patient, which has been supported by Kim et al. (2005). The findings mentioned were important since by chest x-ray, there are no classical findings which may be specifically attributed to the pulmonary disease caused by these lung flukes. The findings that have been listed are pulmonary effusion, hydropneumothorax, pulmonary nodules, consolidation, and cysts. There may also be pleural involvement without any parenchymal lesion. When pleural effusion is encountered, it is highly unlikely that parasitic ova will be identified in the pleural fluid. The authors have described the immunoblot analysis of Paragonimus specific antibodies to be the most reliable tool for its definitive diagnosis with a a sensitivity of 90% and specificity of 99%. However when x-ray shows pulmonary infiltrates and the pleural effusion is eosinophilic ELISA analysis for the antibodies can be fairly reliable (Yamazaki et al. 2008). Link to Diagnostic Measures Jeon et al. (2005) has attributed the gradual world-wide spread of this endemic and localized disease to ingestion of raw meat of wild boar apart from intake of raw or undercooked freshwater crab or Cray fish. Although this method is prevalent in Asian countries specially in Japan, there has been increasing reporting from around the world. These are due to increase in number of immigrants, overseas travelers, popularization of ethnic dishes in developed countries, and expansion of food trading worldwide. Therefore, the fact of increased prevalence will affect the diagnosis of any suggestive pulmonary pathology, where pulmonary paragonimiasis would be considered in the differential diagnosis world over. As per these authors, the classic symptoms of pulmonary disease would comprise chronic cough with rusty brown sputum, hemoptysis, pleural effusion, and fever. While investigated, as supported in Mukae et al. (2001) there would be radiographic patchy density, linear infiltration, nodules, pulmonary cavitations, and pleural effusion. Evidently these manifestations may be identical to pulmonary tuberculosis. These authors have summarized the clinical findings which are similar to earlier studies reviewed. However, in a separate section, the authors have presented the chest radiologic findings which are worth noting since this comprises of a comprehensive collection of findings from different groups of patients. These abnormal findings were classified into intraparenchymal lesions and pleural lesions (Mukae et al. 2001). The intrapulmonary parenchymal lesions would comprise of nodular opacities of variable diameters and linear opacities. Along with these, there could be airspace consolidations, also indicated by Obara et al. (Obara et al., 2004). Pleural effusion with hydropneumothorax has been increasingly reported. This study is important since the authors performed this study in a retrospective design based on clinical data. Therefore on the paucity of clinical literature this study provides the base of useful guidelines. The correct diagnosis of this disease is difficult, and misdiagnosis is a common phenomenon. The need for availability of a confirmatory diagnostic method has been highlighted, and the best diagnostic methods from that angle are ELISA and diagnosis of characteristic ova in sputum, bronchial washings, or lung or endobronchial biopsy specimens was highlighted. In this relation, it can also be mentioned that most of the patients studied by bronchoscopy had luminal narrowing, congestion in the mucosa or edema there. Apart from the common symptoms mentioned earlier, other less frequently encountered symptoms were chest pain and fever. The main determinants of these clinical symptoms were found to be the number of infesting parasites, their locations, and the stages of infestation (Jeon et al., 2005). Radiologic Findings Im et al. (1993) reports the details of radiologic findings in pulmonary disease. As reported earlier and as indicated in other literature, the severity and manifestations of the disease correlate will with the stage of the disease and the parasite load. Early radiologic findings may include pneumothorax and hydropneumothorax. There may be focal air space consolidation, nodules, or bronchiectasis. Even from the early stage of linear opacities, with the advanced disease, there may be thin-walled cysts, dense mass-like consolidation, nodules, or bronchiectasis. Pleural lesions occur when juvenile worm migrates into the pleural cavity approximately 3 to 8 weeks after ingestion of the metacercariae. The initial pathologic events in the pulmonary parenchyma as reflected in the experimental studies are focal hemorrhagic pneumonia which appears as patchy air space consolidation, which may migrate in serial x-rays for followup. It has been reported that 45% of the patients with lung fluke will have this problem approximately after 4 weeks of infestation. If the opacity is linear, there can be a detectable bulbous opacity at the end of the linear streak. The streaky opacity may represent worm migration track, which may serve to be the centre of an ill-defined consolidation (Im et al., 1993). Pathophysiology Zarrin-Khameh et al. (2008) has informed us that this disease is also known as "endemic hemoptysis, Mason hemoptysis, pulmonary distomiasis, and parasitic hemoptysis." This article is important since this is one of the few which indicate the pulmonary pathologic changes caused by this parasite. Although it takes somewhere between 65 to 90 days for the full development of the fluke, the symptoms may begin earlier. The eggs are shed surrounding the worm, and the contents rupture into the bronchioles, so the ova can be detected in the sputum. Pathologically, this disease is caused by inflammation and fibrosis initiated by the worm in the pulmonary parenchyma. Therefore, quite rightly the manifestation can be correlated with the duration of infection and the intensity of the infection. Both the flukes and the eggs would initiate inflammatory response, which predominantly is an eosinophilic inflammation with formation of a fibrous capsule. Consequently, when the cysts rupture into the bronchioles, they would extrude blood, eggs, and other exudates which are inflammatory in nature. It has been suggested that these produce host specific nitric oxide response, which act as an immune mediator. Histologically, the fibrous or granulomatous reactions are associated with the eggs. Frequently, secondary bronchopneumonia is encountered. Pleural involvement is frequently seen and may be associated with an eosinophilic empyema, which can pose a diagnostic problem due to similarity with pulmonary tuberculosis. Fibrosis is more often encountered with a long-standing lesion, where the extent of inflammatory response would be mild, and there is a tendency of calcification of these lesions (Zarrin-Khameh et al., 2008). Treatment Although many studies have reported treatment of this condition with orphan drug praziquantel, Calvopina et al. (1998) has indicated that for human pulmonary paragonimiasis, triclobendazole can be an effective alternative to praziquantel with its efficacy compared with that of the later. In this open clinical trial, the authors compared a dosage regimen of 5 mg/kg once daily for 3 days, 10 mg/kg twice one day, and 10 mg/kg as a single dose. In comparison to praziquantel, the clinical efficacy and tolerance in terms of adverse reactions are better in triclobendazole. There were no hepatorenal or hematological adverse effects. Triclobendazole in all of the above dosage regimens produced quicker favorable parasitological response. The authors concluded that triclobendazole may be the alternative drug of choice in patients with human lung fluke, and it may be better tolerated with quicker and more complete response (Calvopina et al. 1998). Conclusion In this review, the parasitic life cycle of human lung fluke has been revealed briefly, which has been correlated with the endemicity of global spread of the disease. This disease frequently involves the lungs with symptoms which are often delayed to appear. Due to its increasing prevalence, the possibility of this differential diagnosis should be considered with pulmonary pathology, symptoms of unknown origin. Recent diagnostic procedure such as complete blood count, chest x-ray, Ct scan of the chest, ELISA test may be used for definitive diagnosis, while still demonstration of ova in the sputum or lung biopsy specimens could be the most dependable diagnosis. While praziquantel has been traditionally used, recent evidence shows that triclobendazole can be a better drug of choice, but changes in food habits of the population can be the mainstay of prevention of this problem. Reference List Calvopina, M., Guderian, RH., Paredes, W., Chico, M., and Cooper, PJ., (1998). Treatment of human pulmonary paragonimiasis with triclabendazole: clinical tolerance and drug efficacy. Trans R Soc Trop Med Hyg; 92(5): 566-9. DeFrain, M. and Hooker, R., (2002). 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AJR Am J Roentgenol 185: 616-621. Ligh, RW., (2001). Pleural Diseases. 4th ed. Lippincott Williams & Wilkins, Philadelphia: 48-50. Mizuki, M., Mitoh, K., Miyazaki, E., and Tsuda,T. (1992).A case of Paragonimiasis westermani with pleural effusion eight months after migrating subcutaneous induration of the abdominal wall. Nihon Kyobu Shikkan Gakkai Zasshi; 30(6): 1125-30. Mukae, H., Taniguchi, H., Matsumoto, N., et al., (2001). Clinicoradiologic features of pleuropulmonary Paragonimus westermani on Kyusyu Island, Japan. Chest 120: 514-520. Obara, A., Nakamura-Uchiyama, F., Hiramatsu, K., Nawa, Y., (2004). Paragonimiasis case recently found among immigrants in Japan. Internal Med 43: 388-392. Singh, TS., (2002). Occurrence of the lung fluke Paragonimus hueitungensis in Manipur, India. Zhonghua Yi Xue Za Zhi (Taipei); 65(9): 426-9. Singh TS, Sugiyama H, Umehara A, Hiese S, Khalo K. Paragonimus heterotremus infection in Nagaland: A new focus of paragonimiasis in India . Indian J Med Microbiol;27:123-7. Yamazaki, M., Ohwada, A., Miyaji, A., Yamazaki, H., Nara, T., Hirai, S., Fujii, H., Uekusa, T., Suzuki, M., Iwase, A., and Takahashi, K., (2008). Pulmonary Paragonimiasis with Coincidental Malignant Mesothelioma. Inter Med; 47: 1027-1031 Zarrin-Khameh, N., Citron, DR., Stager, CE., and Laucirica, R., (2008). Pulmonary Paragonimiasis Diagnosed by Fine-Needle Aspiration Biopsy. J. Clin. Microbiol.; 46: 2137 - 2140. Read More