We found Paragonimus westermani in Manipur !

Dr T Shantikumar Singh *

Life Cycle of Paragonimus Westermani - Pix: parasitesinhumans.org

Lung fluke infection or Oriental lung fluke infection also known as endemic haemoptysis (coughing up blood) is one of the most important parasitic diseases widely distributed in Asia, Africa, America and former USSR, but not known to occur in Europe, Australia, and Antarctica. The medical terminology of the lung fluke infection is pulmonary paragonimiasis which will be used in the text subsequently. The disease is endemic in China, Japan, Korea, Vietnam, Indonesia, Taiwan, Thailand, Philippines, Belgium Congo, Nigeria, Cameroon, Peru, Ecuador, Colombia, Venezuela and Mexico. It has been estimated that about 293 million people are at risk and 20 million people are affected by paragonimiasis in the world. In India, paragonimiasis was reported in many mammals such as mongoose, dogs, cats, panther and tigers.

However, human paragonimiasis was not considered as an important parasitic zoonosis and never even included in the medical curriculum in India. Most medical doctors were unaware of the prevalence of paragonimiasis in India until recently. Even those few who are aware of the disease would dismiss it as just another rare member of the constellation of parasitic zoonosis, occurring only in the Orient.

The parasite

The lung flukes are the trematode (Flat, leaf like) parasites of the genus Paragonimus. About 50 species including synonyms are distributed in tropical, temporal and sub-arctic zones worldwide. In Asia alone, 23 Paragonimus species have been described of which P. westermani Kerbert, 1878, is the most widely distributed and common human pathogen except in Thailand, Vietnam, Laos and recently India where P. heterotremus has been recognized as the human pathogen.

Life cycle

The parasites require a variety of snail species and mountainous crustaceans (crabs and crayfish) as first intermediate and second intermediate hosts for development of various larval stages respectively and complete the life cycle in mammals and humans as definitive hosts which harbor adult worms. The adult worms usually in pairs remain encysted in the lungs of the definitive hosts and discharge eggs. The eggs are excreted through the sputum and faeces to the external environment. For the continuation of life cycle the eggs have to enter water in the mountain stream or river and hatch miracidium which infect snail hosts. In the snail hosts the miracidia develop into cercariae. The cercariae infect crabs and crayfish and develop into metacercariae (larval stage) which is infective to human and mammalian hosts when ingested.

Infection in humans

Humans acquire infection after the consumption of raw or inadequately cooked crabs and or crayfish that harbor metacercariae. The metacercariae are killed if the crabs or crayfish are adequately cooked, so ingestion after proper cooking will not cause infection. Infection is common in countries where people consume raw or inadequately cooked crabs and crayfish.

In Manipur raw or improperly cooked crabs are consumed for a variety of reasons, as delicious dish, dietary supplement of protein, to enhance physical strength and immunity and as folk medicine. In the market fried crabs are commonly sold along with other dishes which have attracted many people after day's work or office. A popular Manipuri dish, "Waikhu ametpa or Waikhu Singju" wherein raw or roasted crabs are crushed with chilies, onion, garlic and ginger specially made at home, or local liquor vendors is a delicacy taken with alcoholic beverage.

In addition, local customs and superstitious beliefs that ingestion of raw crab extract as folk medicine will cure certain ailments such as fever, allergy, asthma, malnutrition and skin diseases as practiced by some tribal communities contributed to high rate of infection. Interestingly, similar preparation and practice are found in other countries for example, in China "drunken crab" (live crabs soaked in wine overnight), in China and Korea "Kejeng" (live crustaceans are eaten with soy bean sauce), in Japan "Oboro-kiro" (crab juice with bean paste soup), and in Philippine "kilano" (raw crabs with citrus fruit juice and coconut milk taken with alcoholic drinks).

Crayfish juice is given orally in the treatment of measles as folk medicine in Korea and raw crabs are eaten for boosting fertility in women in Cameroon, Africa. These practices are important causes of paragonimiasis. Consumption of raw or insufficiently cooked meat of paratenic hosts such as wild boar and pig is another possible mode of transmission of infection.

Unlike tuberculosis paragonimiasis does not spread directly or indirectly from person to person as the eggs passed in the sputum are not infective to human and animal hosts. Also, the larval stage found in the snail hosts is not infective to humans; therefore, consumption of snails does not cause infection in man.

Disease

The disease caused by the lung flukes is called paragonimiasis which is classified into two broad groups, pulmonary paragonimiasis (infection in the lungs) and extrapulmonary paragonimiasis (infection in sites other than the lungs). Pulmonary paragonimiasis is the commonest form of paragonimiasis but infection in brain and subcutaneous tissue are not infrequent. Majority of patients are asymptomatic, few patients may have mild to moderate symptoms for several months or even years before they visit doctors, if they ever seek medical treatment at all.

Despite the mild nature of the infection, pulmonary paragonimiasis remains as important cause of chronic morbidity. Death may occur due to severe recurrent haemoptysis and infection involving brain and heart. Chest pain, cough, spiting of blood or recurrent haemoptysis and difficult breathing are the most common symptoms of pulmonary paragonimiasis.

The respiratory symptoms and chest x-ray findings are similar to pulmonary tuberculosis often leading to misdiagnosis and treatment of pulmonary paragonimiasis for pulmonary tuberculosis. This diagnostic confusion between pulmonary paragonimiasis and pulmonary tuberculosis will have significant impact on the outcome of the RNTCP in Manipur. Cerebral paragonimiasis with symptoms similar to space occupying lesion in the brain and cutaneous form presenting as migratory subcutaneous nodule are common extrapulmonary paragonimiasis.

Differential diagnosis

All the patients presented with spitting of blood or recurrent haemoptysis should be investigated for paragonimiasis, tuberculosis, pneumonia, brochiectasis, aspergillosis, hydatid disease, cystic fibrosis and cancer.

Diagnosis

A positive history of consumption of crabs and crayfish in a patient of haemoptysisis is a sufficient clue to investigate for paragonimiasis. A definitive diagnosis can be made by the microscopy demonstration of the characteristic Paragonimus eggs in the sputum and or stool samples. Nowadays, highly sensitive and specific serological tests including rapid tests are available for the diagnosis of paragonimiasis. The serological tests are useful for the diagnosis of paragonimiasis in which Paragonimus eggs are absent or cannot be demonstrated in the clinical specimens, however, the availability of the tests are restricted to the countries like Japan and China where these are produced.

Treatment and prevention

There are three major antihelminthic drugs namely; Praziquantel, Bithionol and Triclabendazole currently available for use in the treatment of paragonimiasis. Of these, Praziquantel (eg Biltricide manufactured by Bayer) is the drug of choice for the treatment of paragonimiasis. The recommended dose is 25 mg per kg body weight 3 times a day after meals for three days. The author found relapse in 2% of the cases with the 3-day regimen and has recommended for 5-day regimen for almost a 100% cure. The drug is not easily available in the market in Manipur and expensive for the poor patients to afford.

Research on Paragonimus and paragonimiasis in Manipur

In India, the first human case of paragonimiasis was reported from RIMS, Manipur in 1982. Thereafter, a serological survey conducted in the Imphal East district in 1993 had revealed a prevalence rate of 6.7% and over the years through 2010 about 300 parasitologically confirmed cases have been detected. Since 1990s, paragonimiasis has striven to gain recognition as a significant food borne parasitic zoonosis in India, especially in the northeast States.

There seems to be little justification for this neglect by the health department and public health providers, however, since there have been growing evidence of endemic areas not only in Manipur, but also in Nagaland and Arunachal Pradesh. The data available on the prevalence and incidence of the disease, till today, may be just the tip of an iceberg as the study areas covered are few and limited and many cases have remained undiagnosed.

The first scientific research work on paragonimiasis in Manipur was conducted in the Regional Institute of Medical Sciences where all the patients who were attending RIMS Hospital with haemoptysis were investigated for paragonimiasis during the period from 1983 to 1986. The investigation revealed that almost all the patients who were diagnosed and treated for smear negative pulmonary tuberculosis were in fact suffering from pulmonary paragonimiasis. The findings were published in the Transactions of Royal Society of Tropical Medicine and Hygiene (1986) which attracted researchers from abroad, mainly Japan and China for a joint research on Paragonimus and paragonimiasis in Manipur, India.

In 1990, the first Indo-Japan joint research work on Paragonimus and paragonimiasis was conducted in the department of microbiology, RIMS, Imphal. The results of the collaborative and independent research studies in Manipur, Arunachal Pradesh and Nagaland have revealed valuable information in understanding the parasite and the disease. For the first time in India, the fresh water crabs, Indochinamon manipurensis (formerly Potamiscus maipurensis) in Manipur and Nagaland and Barytelphusa lugubris in Arunachal Pradesh were found to harbor more than one type of Paragonimus metacercariae. The occurrence of P. miyazakii manipurinus n. sub sp., P. hueit'ungensis, P. skrjabini, and P. heterotremus were reported from Manipur.

Of these P. heterotremus has been confirmed as the agent causing infection in humans in Manipur, Nagaland and Arunachal Pradesh. We were amazed by this discovery as we expected P. westermani would be the causative agent of human paragonimiasis in India from where the species was first described by Kerbert in 1878 in the lungs of a Bengal tiger which was captured in India and died in the Amsterdam zoological garden in Holland more than a century ago. Also, P. westermani infection in mammals in India is common. However, our interest in P. westermani persisted because this species has been described as the commonest human pathogen and widely distributed in Asia.

In June 4-6, 2011 Dr. H. Sugiyama from NIID Tokyo, Japan and I travelled to Moreh to investigate paragonimiasis. With the help Dr. Nandakishor and his team of doctors posted at Moreh hospital and local Kuki student volunteers we have conducted the research work on May 5, 2011. We found few seropositive paragonimiasis patients and could isolate a dozen of Paragonimus metacercariae from the crabs collected at lailok mountain streams.

We brought back the metacercariae for further morphological and molecular characterisation and laboratory animal infection. Dr. Sugiyama is responsible for molecular characterisation (DNA sequencing of worms at various developmental stages) and Dr. T. Shantikumar is responsible for morphological characterisation of the worms and case studies in India.

"We found Paragonimus westermani in India: Sugi@Tokyo" was the email message received from Dr. Sugiyama on June 2011.

Conclusion

We are extremely happy and so excited to discover this species after about two decades of our relentless pursuit for P. westermani in Manipur. Our next research plan will be morphological and molecular characterization of adult worms and eggs of P. westermani and its association in human paragonimiasis in India.

The main purpose of publishing this piece of work is to generate knowledge of paragonimiasis (lung fluke infection) among health care professionals and public health officials in Manipur for appropriate action for detection and treatment of cases and its preventive measures. Paragonimiasis is an important food borne parasitic zoonosis which in most instances are subclinical, however, chronic infection causes high morbidity and sometimes, severe infections may cause death. The disease is otherwise curable and preventable.

Acknowledgement

We thank Dean, SMIMS, Sikkim, Director, RIMS, HOD Microbiology, RIMS, Manipur, Doctors and staff of Moreh hospital, Moreh, and Director, NIID, Tokyo, Japan for permission and assistance in conducting the research work. Thanks are due to security personnel, Government officials, friends and local people in Moreh who help us in many ways the research program a success.