Parasitic Lung Diseases Death and Dilemma

Home , Parasitic pneumonia, Tropical eosinophilia

International Journal of Open Medicine and surgery

Review | Vol 1 Iss 1

Raghavendra Rao M.V*1, Abrar A khan2, Vijaya Kumar C3, Badam Aruna Kumari4, Mohammed Khaleel5, Mohammed Ismail Nizami6, Jithendra K.Naik7,Mahendra Kumar Verma8 *1Scientist-Emeritus, and Director of Central research laboratory, Department of Laboratory Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, TS, India. 2Dean, American University School of Medicine Aruba, Central America. 3Professor, Department of Pulmonology, Apollo Hospitals, Jubilee Hills, Hyderabad, Telangana, India. 4Associate Professor, Department of Respiratory Medicine, Apollo Institute of Medical sciences and Research, Hyderabad, TS, India. 5Professor of Microbiology, Clinical & Diagnostic Microbiologist, Department of Microbiology, Deccan college of Medical Science, Hyderabad, TS, India. 6Department of Emergency Medicine NIMS, Punjagutta, Hyderabad, TS, India. 7Department of Zoology, University college of Science,Osmania University. 8Department of Biotechnology, Acharya Nagarjuna University, Guntur, AP, India

*Corresponding author: Dr. M. V.Raghavendra Rao, Scientist-Emeritus and Director of Central research laboratory, Department of Laboratory Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana State, India, E-Mail: [email protected]

Received: 14 July 2020 Accepted: 19 July 2020 Published: 25 July 2020

Abstract Warm countries are the worm countries. We are living in the"Wormy world" "Delays have dangerous ends" We take our breathing and our respiratory health for granted, but the lung is a vital organ that is vulnerable to airborne infection and injury. The parasites produce toxic metabolites and increase eosinophilic eosinophils induce tissue damage. protozoans, Nematodes and Trematodes affect the lungs. Echinococcus produces hydatid cysts. Lesions are discovered on the Chest X- ray during asymptomatic primary infection. Dirofilaria immitis produce chest pain, cough, haemoptysis, wheezing symptoms. In Amoebic liver abscess, primary complication that encounters is Amoebic pleuropulmonary disease. Ascaris larvae invade lung tissue and produce Loffler's syndrome. Similarly, hookworm larvae, Strongyloid, Schistosome larvae produce the similar pulmonary symptoms. Wucheraria bancrufti, Brugia malayi produce tropical eosinophilia. Keywords: Loeffler's syndrome, Eosinophilic pneumonia, Wucheraria bancrufti, Human pulmonary dirofilariasis (HPD), Paragonimus westermani, Microfilaria

Citation: Raghavendra RMV. Parasitic Lung Diseases Death and Dilemma. International Journal of Open Medicine and Surgery.

INTRODUCTION Parasitic infections are seen all over the globe in general and in immunocompromised patients in particular. Echinococcus granulosus produce hydatid cysts. It takes years for full formation of cysts, during this time, patients are asymptomatic [1].

The cysts are seen in X-Rays accidentally. The cyst contains hydatid fluid and salts. The cysts cavity producing “Water Lilly sign” [2].

The adult heart worm lives in heart and nearby blood vessels of dog and cause the dog to have cough, shortness of breath and weakness [3].

The trophozoites into the bronchial airways after the rupture of abscess. Swelling and redness appears on the pleura of lung [4]

Practitioners should misdiagnose this as Tuberculosis, as the clinical symptoms like fever, cough, weight loss are almost match to TB. However, in endemic areas it is present to consider Paragonimus westermani as well [5].

Paragonimus westermani, is a trematode parasite. It is the parasite of lung primarily but infects other parts of the body. Ova can be observed in microscopic examination of sputum, faeces and pleural fluid [6].

A -year-old male with history of Down syndrome who presented with severe right side pneumonia and empyema. He is resistant to regular medical therapy. Patient was diagnosed as Pleuropulmonary amoebiasis, observing trophozoites in pleural fluid. Patient recovered from the disease on metronidazole therapy [7].

Tropical (pulmonary) eosinophilia, or TPE, is characterized by coughing, asthmatic attacks, and an enlarged spleen, and is caused by Wuchereria bancrofti, a filarial infection. Tropical pulmonary eosinophilia is very common in India and Southeast Asian countries. This disease also mimic with tuberculosis, asthma, or coughs related to roundworms [8].

Tropical pulmonary eosinophilia or Weingarten’s’ lung resembles T B. with low grade fever, cough, loss of weight symptoms [9].

In tropical pulmonary eosinophilia or Weingarten’s’ lung or Eosinophilic lung, chest X-ray shows “mottling’s” like TB X- ray. The link has been established with Wuchereria bancrofti and Brugia malayi [10].

Research on the Infections of the Lower Airway Protozoan and Helminth parasites, and their larvae cause infection in lower air way.

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The mucus membrane of this part the air way is probably sterile in health, but direct examination involves bronchoscopy or lung biopsy, neither of which is indicated in the normal course of the diagnosis of infection. Sputum from subjects with acute excerbarations of chronic bronchitis and pneumonia, should be examined.

The more purulent material is likely to contain specific pathogens and therefore examination should be directed to this part by spreading the sputum in a dish so that the purulent material may be picked directly for observing larvae if any. (Mackie and McCartney) Pulmonary defenses Most microbes are small and can penetrate to the distal gas exchanging surfaces of the lung, although the majority are excluded by the defenses of the upper airways are to be cleared by the mu co ciliary as escalator.

Humeral factors, including secretory immunoglobulin A(SIgA) and defensins released y air cells, limits microbial penetration in to tissues. Air way mucosal cells trap microbial antigens and transport them to regional lymph nodes, where they both T and B lymphocytes, evoking adaptive immunity ulceration or thickening of the gas exchange surface limits diffusion of o2 and co2.

For this reason, the alveolus, under normal conditions, is maintain sterile by resident macrophages that scavenge inhaled particulates and secrete mono-kines, including interlukin 10 and transforming growth factor Beta, that locally supress inflammation and promote non-tolerance. If the alveolar lining is injured or if the number of invading organisms exceeds the phagocytic capacities of resident macrophages, nutrophils and exudation of monocytes are recruited to sites of lung infection [11].

Parasites induced eosinophilic lung diseases Pulmonary Ascarisis. The larva of Ascaris, Rhabditiform produce peribronchial inflammation, increased mucus production and bronchospasm. The larvae produce Loffler's syndrome. The patients may present with general symptoms of malaise, loss of appetite, headache, myalgia and fever lasting 2 or 3 days. The respiratory system include chest pain cough with mucoid sputum, haemoptysis, shortness of breath and wheezing.

Pulmonary Amoebiasis Pulmonary amoebiasis is not a common clinical presentation. In India and many other tropical contries, one does come across pulmonary amoebiasis. So long as the disease is not recognized, it is a clinical problem, which is quite baffling to the uninitiated, whereas once recognized and the treatment instituted, the clinical result will be very gratifying to all concerned.

In most cases the condition is missed not because the clinician is not aware of the possibility. In the tropics whenever one gets a problem chest case, where the presentation is like pneumonia or lung abscess or pleural effusion or any other lung manifestation, or one must think of the possibility of pleuro pulmonary amoebiasis. The disease is rare at either extremes of life and the reason for this is,all the extra intestinal amoebiasis are common in alcoholics. The incidence of complications started declining [12].

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Pulmonary ancylostomiasis and Pulmonary strogyloidiasis. Ancylostoma duodenale larva, the (Filariform) penetrate the intact skin and reach lungs. It produces fever, cough. Wheezing and transient pulmonary infiltrates in chest radiographs.

It is associated with Pulmonary eosinophilia Pulmonary strogyloidiasis, the females live in the wall of intestine of man; The rhabdity form metamorphose into filariform. This larva reaches the lungs through circulation. In lungs, the larvae produce bronchopneumonia, and hemorrhages in the alveoli. This is associated with elevated eosinophilia and IgE. Gram negative bacteria are carried by large on their cuticle.

As a result of invasion of bacteria along with larvae diffuse and patchy bronchopneumonia and pulmonary abscess can occur.

Tropical Pulmonary Eosinophilia or Weingarten’s’ Lung or Eosinophilic Lung, It is by Brugia malayi and Wucheraria TPE is pervasive in endemic regions of the world.

Patients suffer from fever, cough and massive eosinophilia. This is described as pseudo-Tuberculosis condition. It is called wingarten syndrome [13].

Pulmonary dirofilariasis, Visceral larva migrans, Pulmonary richinellosis, schistosomiasis, Paragonimiasis, Hydatid, Eosinophilia and pulmonary tuberculosis, and Brucellosis. Fungus induced eosinophilic lung disease are Coccidiomycosis, Aspergillosis, Cryptococcosis and Histoplasmosis. Clinical features of TPE- Paroxysmal cough and wheezing, Weight loss, low grade fever, lymphedenopathy and pronounced blood eosinophilia

Characteristically total serum IgE levels (4-40 KIE levels/mL) and essentially antifilarial antibody levels are markedly elevated. In TPE, microfilariaelarva antigens rapidly cleared from the blood stream by large eater cells

In some patients trapping of microfilariae and other reticuloendothelial organs can cause hepatomegaly, spleenomegaly or lymphedenopathy. Differential diagnosis TPE must be distinguished from asthma, Loffler, syndrome, allergic bronchopulmonary aspergillosis, allergic granulomatosis, other systemic chronic eosinophilic pneumonia and the hypereosinophilic syndromes.

Pulmonary eosinophilia A 25-year-old male patient presented with cough white mucoid sputum, breathlessness and fever of 2 months duration.

He didn’t complain loss of appetite, loss of weight. He was a non-smoker, non-alcoholic. He didn’t have any comorbidities like diabetes, hypertension, bronchial asthma or pulmonary tuberculosis. On examination there was no cyanosis, clubbing ,pedal edema. On auscultation there were crepitations on right lower chest. Cardiovascular, abdominal and neurological examinations were normal. His vitals were stable. Room air saturation was 98%. His hemoglobin was 17gm/dl, there was leukocytosis (16800 cells/cumm) and eosinophil count was 11,592 cells (69%).His chest x ray (Figure-1) showed nonspecific haziness along with prominent bronchovascular markings through out lung fields. CT scan of chest (Figure-2) 15

www.ijomasr.com | JULY-2020 showed bilateral miliary nodules over all lung regions. Bronchoscopy with transbronchial biopsy was done. Bronchoalveolar lavage and biopsy revealed pulmonary eosinophils in the alveoli. With a combination of miliary mottling on imaging and eosinophils in bronchoscopy patient was diagnosed as a case of TPE, started on DEC along with steroids. His symptoms improved and discharged in a stable condition. Pt was lost for follow up

FIG 1 . Bilateral prominent broncho vascular markings.

FIG 2. Bilateral miliary nodules along bronchovascular distribution Main Research Hypothesis of Parasitic Lung Diseases

Paragonimus westermani, Toxocara spp., Clonorchis sinenis, Spirometra spp. and Taenia solium, etc cause pleural parasitic diseases [14]. The large eater cells are programmed in response to signals originating from the lung tissue environment [15]. Alveolar large eater cells are special and peculiar cells and move freely on the outer surface of lung, phagocytise the cysts and other parasitic debris [16].

Most of the Protozoan and Helminth lung parasites, their respective trophozites, larvae, cysts, toxic metabolites produce allergic manifestations in bronchi, bronchioles, alveoli and cause infection. These manifesttions misdiagnosed as lung cancer/TB [17]. 15

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Pulmonary abscess is a rare manifestation that is due to the Entamoeba trophozoites. The clinical symptoms are similar and initially treated for T B or lung cancer. Parasitic lung Disease-Good Research Study objective very rarely amoebic liver abscess occur in brain, Spleen, Lungs or d body wall. The trophozoites, cysts block the air way. nSome of the nematode larvae also block the air way and produce inflammation [18].

Ambulatory/perambulent/AIDs patients mainly affect the parasitic lung infections all over the globe Major Pulmonary parasitic discoveries Entameba histolytica is a causative protozoan for amebiasis, and particularly affects developing countries.

Amebae were first found in fecal samples by Feder Losch in 1875 but only attributed the maintenance of the inflammatory process to them, not the dysentery. Fritz Schaudinn in 1903, proved the Losch’s discovery and Endameba coli. Schaudinn named Losch’s parasite as E. histolytica.

The existence of a disease producing and non-disease producing was confirmed by further research by Sargeaunt and Williams in 1978), William Petri et al in 1987 and Diamond and Clark in 1993. The World Health Organization accepted this hypothesis in 1997 [19].

Alveolar echinococcosis (AE) results in humans infected by the metacestodes of Echinococcus multilocularis (EM), mainly through travel and domestic dogs. AE is a major global public health issue (most reported in China, Central Asia, the Middle East and some parts of Europe) [20,21].

The disease can progress to hepatic alveolar echinococcosis (HAE).

Another species of the same genus, Echinococcus granulosus (the canid tapeworm), causes in its larval stage, the most serious human disease caused by a larval cestode- Cystic echinococcosis (CE). CE results from accidental infection of humans with larval stages from dogs and sheep [22].

The history of echinococcosis, like that of malaria, is long. There are also descriptions of hydatid cysts in humans in the works of Hippocrates, Galen and in later European medical texts AE was identified as a disease entity in humans only in the middle of the 19th century. A significant progress has been achieved in echinococcosis research in the 20th century but CE and AE are still not fully recognized [23].

Diagnosis of Lung Parasites The clinical diagnosis is a first and most crucial step in the process of finding therapeutic disease. There are several approaches are being used in clinical diagnosis including routine laboratory tests as conventional methods and also rapid and robust modern methods. Both the approaches have their significance in the clinical diagnosis of the disease In the current scenario, there is a need for rapid and robust diagnostics as global disease burden is prevailing. 15

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Pulmonary function tests Measurement of the forced expiratory volume1 second (FEV1) and (FVC) [24].

Diagnosis of pulmonary Amoebiasis Demonstration of the trophozoites of Entamoeba histolytica in the sputum and by other immunological tests.

The sputum, pleural fluid of Protozoan Helminth parasites may not be detected in the first expectorations but will be found in subsequent expectorations [25].

In pulmonary Pulmonary strogyloidiasis infection examination of the sputum will demonstrate the presence of rhabdtiform larvae The most common clinical presentation is Ascaris pneumonitis. Larvae are seen in sputum.

A Chest X-ray can confirm the presence of larvae, and stool microscopy is adequate in established infections. [26].

Pneumocystis carini is diagnosed by observing the lung biopsy or bronchial brushing. Serological tests will not give good results [27].

Commonly used drugs for treatment to Pneumocystis carini are Pentamidine, isethionate or trimethoprim sulpha methoxazole [28].

Pulmonary eosinophilia should always be suspected in patients with un explained radiographic opacities in lungs, either localized or diffuse [29].

It can readily be mistaken for pulmonary tuberculosis or bacterial pneumonia unless an eosinophil count is carried out. After the diagnosis is established, an attempt should always be made to discover the relevant etiological factor, such as an intestinal helminth, or filariasis or treatment with a drug or exposure to a chemical substance previously reported to have caused the disease.

Research on Inflammatory Response Tissue injury such as that following the establishment and multiplication of microorganisms, call forth an inflammatory response. This begins with local arterioles and capillaries, from which plasma escapes. Edema fluid accumulates in the area of injury, and fibrin forms a network and occludes the lymphatic channels, tending to limit the spread of organisms.

Polymorph nuclear leukocytes in the capillaries stick to the walls, and then migrate out of the capillaries towards the irritant. This migration is stimulated by substances from the inflammatory exudate (chemotaxis) The phagocytes engulf the microorganisms and intracellular digestion begins. Soon the PH of the inflamed area becomes more acid, and the cellular proteases tend to induce lyses of the leukocytes. 15

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Large mononuclear macrophages arrive on the site and, in turn, engulf leukocyte debris as well as microorganisms and pave the way for resolution of the local inflammatory process. Among probable mediators of the inflammatory response are lymphokines and derivatives of arachidonic acid, including prostaglandins leukotrienes and thromboxanes. Drugs that inhibit the synthesis of prostaglandins (by blocking the enzyme cyclooxygenase) acts as inflammatory agents.

Current research on lung parasites Parasitic pulmonary diseases usually produce, cough, fever, malaise, blood tinged sputum. Even experienced physicians sometimes misled them as bacterial, viral and fungal. It may be parasitic too. Observe sputum, pleural fluid and search microscopically for trophozoites/larvae and cysts. Lung diseases produced by parasites, their larvae are curable [30].

Pneumocystis carini It is a sporozoan protozoan parasite. It will not cause any ill health to rats, mice and dogs. In infants it causes the disease interstitial plasma cell pneumonitis. In AIDS patients it causes death.

Entameba histolytica Debnath et al (2019) have published a review paper which collates 29 articles by 167 authors and, as claimed by the authors, presents the most recent development in this field through literature classifying into four sections - drug discovery, cell biology and signalling, and pathogenesis and immunity. Another thorough review by Kantor et al (2018) on E. histolytica and E. dispar and provides insight into new vaccine development [31,32].

WHO, listed Echinococcosis, as a neglected parasitic infectious disease.

To raise the awareness of cystic echinococcosis (CE) among general public and policy makers of the European countries to the magnitude of the problem, the HERACLES, collaborative project was designed in 2013 by WHO and Department of Infectious diseases, Italy. (HERACLES, 2013) [33,34].

Current Treatment for Pulmonary parasitic infections Ascariasis Mebendazole 100 mg bd x 1 day or Abendazole 400 mg one dose or Pyrental 10 mg/kg one dose or Lavamisole 150 mg one dose Hook worm Mebendazole 100 mg bd X 3 or Albendazole 400 mg or Pyrental 10/kg od X 3 Strongyloidiasis Thiobendazole 25 mg/kg/day X 5 days or Albendazole 400mg/kg X 3 days Hydatid disease Albendazole 10- 20-mg/kg/day for 4-6 weeks Schistosomiasis Praziquantel single oral dose of 40 mg/kg 0r 60 mg/kg in three divided doses for one day Lymphatic filariasis DEC Ivermectin with DEC or Albendazole Amoebiasis Diloxanide fuorate Metronidazole or Tinidazole or Secnidazole followed by Diloxanide furoate [35].

Strengths and Limitations of the Lung parasitic research.

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Many protozoan and helminth parasites affect lower air way. The adult worms,larvey and cysts block the air passage. These parasites produce toxic metabolites and produce inflammation [36].

Prevention and control of lung parasites Wucheraria has no animal reservoir. The recommended treatment is Diethylcarbamazine ( DEC) Treatment may have to be repeated in endemic areas, every two years or so. Mass chemotherapy has been tried, but it may pose difficulties in large endemic areas such as India.

As DEC is non-toxic, it can be safely administered in combination with food items such as common salt. Schistosomiasis, can be prevented destruction of snail vectors in endemic areas and avoidance of swimming bathing and washing in infected areas. Strongyloidiosis can be prevented by treatment of carriers and diseased persons simultaneously wholesale treatment of community. Prevention of soil pollution by proper control of sewage disposal. Disinfection of faeces or soil

Personal cleanliness and elementary hygienine is mandatory. Protection of water supplies from faecal pollution. Direction and isolation of carriers. Paragonimmiasis can be prevented by eradication of molluscan hosts and avoidance of consumption of raw, freshly salted or inadequately cooked crabs and crayfish as food.

CONCLUSION The patient must always be asked about symptoms such as cough, sputum, haemoptysis, breathlessness, wheeze and nasal discharge. Infections of respiratory tract may be caused by viruses, bacteria and fungi. Parasites cause many respiratory diseases. But the physicians, Scientists are neglecting the parasitic diseases.

In protozoal infections, the lesions are greatly influenced by proliferation multiplication metastasis to to distant organs including lungs. In Entamoeba histolytica the trophozoite form secretes a powerful histolytic toxin causing destruction of the tissues. The effects produced therefore depends upon their habitat ie the sites where the parasites attack the tissues on the pattern of laying eggs or larvae.

In certain helminth infections, the normal secretion and excretion of the growing larvae in lungs and the products liberated from the dead parasites behave the foreign proteins and give rise to various allergic manifestations. In some helminthic infections, the migrating larvae carry viruses and Gram negative bacteria from the intestine to the blood and lungs as in strongyloidiasis andascariasis.

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