Blood Fluke

 

Blood flukes

PKGhatak,MD

Blood Fluke infection is the 3^rd flatworm (Trematode) parasitic disease of humans discussed here, Liver fluke and Lung fluke were the other two mentioned in the earlier blogs.

Schistosoma hematobium is the parasite and the disease produced by the worm is called Schistosomiasis, also known as Bilharziasis and Snail fever. Schistosoma means a split- body. The shorter and stouter adult male has a longitudinal cleft along the length of the body and in that space, a slender, longer female worm is held in embrace by the male for its life. A German doctor, Theodor Maximilian Bilharzia, while serving in Egypt, discovered the flatworm parasite in 1851, and the disease is named after him.

Two distinct illnesses are produced by Schistosoma species.

1. Urogenital Schistosomiasis. Produced by S. hematobium. The worms reside in the venules (small veins) of the urinogenital organs.

2. Gastrointestinal & Biliary Schistosomiasis. Several Schistosoma species are responsible and they are named according to the initial case originating country. The parasites invade the venules of the GI and biliary systems.

The life cycles of all the species of Schistosoma are identical and closely resemble those of the other trematodes.

Humans are the final host and act as the reservoir of the parasite. Other primates, ruminant farm animals and rodents are additional reservoirs.

Incidence of Bilharziasis.

The WHO estimates 200 million active cases are seen annually. Genitourinary bilharziasis is common in the Nile River Valley of Egypt and the adjoining northern African countries. Gastrointestinal/biliary bilharziasis occurs in China and countries surrounding the South China Sea. It is also prevalent in South America and the Caribbean islands. Indigenous  bilharziasis does not happen in the USA.

Life Cycle of Schistosoma.

Human and animal feces and urine contaminate rivers, lakes and other bodies of water. Digging canals for irrigation has spread the risk of bilharziasis in much wider areas. Inundation during the rainy season is another hazard.

Schistosoma development stages are - Egg, Miracidia, Sporocyst, Cercaria and Adult.

Eggs: An embryonated egg has a spine and the position of the spine distinguishes one species from the other. Each egg is elongated or oval, measuring about 175 X 45 micrometers. Inside an egg, one embryo is in the development stage. A hinged door at the head-end opens and lets a grown larva out in the water.

Embryos: Miracidia larva is 200 micrometers long and covered with cilia and is a free swimmer. Miracidia larva lives in the water only a few hours and must find the proper snails that live in sweet water to multiply and develop further into infective larvae.

Sporocytes: Miracidia after entering inside the snail, move to softer tissue and transform into cysts. Cyst develops many daughter cysts and the daughter cysts move to newer locations and continue to develop into Cercaria larvae.

Cercaria larva is 500 micrometers long, has a tapering head and a forked tail. Cercariae live only 3 days. It takes only a few minutes for cercariae to enter into the body of their victims by penetrating the skin. It drops its tail and moves inside the veins. Inside the blood vessels, it becomes a round ball and is carried by the blood to the heart, lungs, and finally to the liver. In the liver, cercariae develop in about 3 weeks into adult male and female worms.

Adult worms: Adult worms are 7 to 29 mm long, have a cylindrical body, colored grey-white, have two suckers and an alimentary canal but no anus and the body is filled with reproductive organs.

Subsequently, the life of Schistosoma depends on the species and victims.

Schistosoma species	Definitive host	Site of infection	Eggs discharged in	Endemic area
S. hematobium	Humans, other primates	Genitourinary system	Urine	Africa
S. japonicum	Humans, carnivores, ruminantsmesenteric	GI & biliary mesenteric veins	feces	South- East Asia
S. mansoni	Humans , rodents	As above	feces	Africa
S.mekongi	Humans, dogs	As above	feces	South- East Asia
S. intercalatum	Humans, rodents and cattle	As above	feces	South-East Asia

Symptoms: The initial infection produces no symptoms. Some people develop itch at the skin penetration sites and is called swimmers' itch. Some others develop eosinophilia and patchy pneumonia.

Acute symptoms. Eggs produce allergic reactions known as Katayama fever. It manifests as fever, weakness, fatigue and lymphadenitis.

Abdominal pain, low grade fever and eosinophilia develop in others.

Chronic symptoms. Many eggs are carried away to different organs. The eggs get embedded in the tissues and generate immune reactions. The initial inflammatory reaction is followed by tissue necrosis, fibrosis and granuloma formation. Small granulomas coalesce together into polyps.  Polyps are seen in the urinary bladder and esophagus, stomach and intestine.

Genitourinary Bilharziasis: Hematurrhea, painful urination, urinary tract infection, glomerulonephritis, deformed external genitalia, calcified lesions surrounding the embedded eggs in tissues, specially in the urinary bladder are common. Carcinoma of the bladder also develops. Fibrosis of the various components of the reproductive organs leads to difficulty in pregnancy and miscarriage. Blood in semen in a  male patient is a striking feature.

Gastrointestinal and biliary bilharziasis:

Abdominal pain and diarrhea, dysphagia, bleeding varies in the esophagus and stomach producing anemia and malnutrition. Liver and spleen enlargement, anemia and leukocytopenia develop due to hypersplenism. Calcifications of blood vessels lead to various ischemic symptoms.

Distal organ involvement:

CNS. In the brain, the eggs are calcified and cause seizures, headaches and paralysis of limbs.

In the spinal cord: Transverse myelitis is a serious problem

Lungs: In the chronic stage Pulmonary artery stenosis and calcifications produce pulmonary hypertension.

Heart: Myocarditis and heart failure occur.

Diagnosis: Stool examination detects eggs and the shape of eggs and the characteristics of the spine help diagnosis of the schistosoma species.

Egg characteristics:

S.hematobium – Eggs are oval shaped, the spine is long and sharp and attached to the terminal end.

S. japonicum - Eggs are round in shape. The spine is rudimentary and appears like a hook and is attached to the lateral side.

S. mansoni –Eggs are elongated and the spine is attached at the posterior end of a side.

S. mecongi – Eggs are 30-45 micrometers long and have a short lateral spine.

S. intercalatum – Eggs are oval shaped and the spine is attached to the terminal end; Its eggs resemble S. hematobium eggs.

In S. intercalatum infection few eggs are excreted in the feces. The infection in the lower colon and rectum. A biopsy of the rectum is required.

In CNS infection more reliable tests are ELISA antibody test and parasite DNS identification by PCR test.

Treatment: Praziquantel is a very effective drug in killing adult worms but immature worms are not killed. A person is usually infected repeatedly and both mature and immature adult worms are present at the same time. So Praziquantel is repeated weeks later. The Cure rate is 90 %.

Special features of Schistosoma. The adult worm does not produce inflammation or, allergic reactions only the eggs are allergenic.

The adult worm is classified as a flatworm but it resembles round worms. The worms unlike other flukes are not harmaphrodites, the male and female sexes are separate.

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in other primates, ruminants, rodents and cattle.

Adult  The adult worms are 1–2 cm long with a cylindrical body that features two terminal suckers, a complex tegument, a blind digestive tract, and reproductive organs Schistosoma spp. [these species cause schistosomiasis/bilharzia in humans and ruminants]

Parasite morphology: Blood flukes form five different developmental stages: eggs, miracidia, sporocysts, cercariae and adult worms. Eggs are round to oval in shape, operculate (hinged at one end) and contain a developing embryonic larva (miracidium). Differences in egg morphology can be used to distinguish between Schistosoma species: S. mansoni producing oval eggs (115-175 x 45-7µm) with a sharp lateral spine, S. japonicum forming round eggs (70-100 x 50-70µm) with a rudimentary lateral spine; and S. haematobium producing oval eggs (110-170 x 40-70µm) with a sharp terminal spine. Miracidia are elliptical free-swimming larval stages (~200µm long) covered with cilia. Sporocysts appear as pleomorphic sac-like bodies which contain developing cercariae. Mature cercariae are elongate free-swimming larval stages (400-600µm long) consisting of a tapering head (with prominent penetration glands) and a forked tail (furcocercous). Adult flukes are elongate tubular worms (10-20mm long), with rudimentary oral and ventral suckers. Males are shorter and stouter than females, and they have a longitudinal cleft (gynecophoral canal or schist) in which the longer slender female lies folded.

Theodor Maximilian Bilharz 

Regarding Katayama syndrome (a possible clinical manifestation of schistosomiasis in naive patients characterized by fever, cough, myalgia, headache and abdominal tenderness [19]), descriptions fitting its clinical manifestations can be found in ancient books of traditional Chinese medicine referring to more than 2400 years ago

Ascaris lumbricoides

 

Ascaris lumbricoides infestation

PKGhatak, MD.

Ascaris lumbricoides is a foot long intestinal parasite. The human infection has been known since the ancient time. The first written record of human infection was given by Linnaeus in 1758.

Ascaris lumbricoides is a roundworm, the sexes are separate and the female worm is larger in size. Adult worms live in the small intestine of the human. Ascaris also infects pigs, monkeys and other animals. A female ascaris lives one to two years and can lay 200,000 eggs a day. The eggs are mostly fertile but unfertilized eggs are also present in the stool of the victims. If a female worm does not find a male worm, it moves around, and crawls into the throat. If enters the larynx it causes respiratory distress and a bout of violent cough till it is dislodged. It may also come out of the nostrils.

People at risk:

The WHO says about 1 billion people are at risk of infection. The infective state of the worm is the fertilized 3^rd stage eggs or embryonated eggs. Unlike any other parasite, ascaris eggs are well protected by their thick outer shell and can live for 3 years in the soil. People unknowingly swallow eggs carried on their fingers due to their unhygienic habits or ingestion of contaminated water and food. Humans and farm animals act as reservoirs of ascaris.

Life history of Ascaris:

The fertilized eggs are deposited in the soil, either by spraying the human waste on the agricultural land as fertilizer or, by people defecate out in the open. The eggs undergo further development in the soil and become embryonated eggs in 15 -18 days.

Children playing in the darts carry soil and eggs on their fingers or, under their nails. The eggs enter the mouth when children eat with their fingers. The same way adults are infected or, contaminated food and drinks by the food handlers.

Inside the duodenum, the larvae emerge. The larvae move to the lungs for further development. The larvae reach the lungs by way of the Portal vein and finally in the pulmonary circulation. In the lungs, the larvae become juvenile worms in about 15 days. The juvenile worms journey back to the small intestine by way of trachea and are coughed up and swallowed by the victim. Back in the intestine, for the second time, they reach maturity and mate with the opposite sex and begin laying eggs in 3 months from the time of infection.

Researchers are not sure why ascaries larvae must travel to the lungs. Several reasons are put forward but still remain unknown.

 Human disease.

During initial infection. Most of the victims are unaware of infection and remain symptom free. Some develop abdominal cramps and diarrhea.

During migration to the lungs. This period is generally asymptomatic.

The period of stay in the lungs. Symptoms are mostly due to the physical presence of foreign bodies in the airways and all related pulmonary complications, secondary infections and allergic asthma with eosinophilia.

During migration from the lungs to the small intestine. Cough and the horror of live worms being coughed up.

Small intestinal stay. Though the worms do not suck blood like hookworm never the less,  they steal nutrients from the children and children become stunted and malnourished. Motile worms in the intestine can enter the bile duct, gall bladder, and appendix causing acute obstruction and infection. A heavy parasitic load in the small intestine causes bowel obstruction.

During adult female searching for a male worm. When the worm reaches the pharynx and sometimes enters the larynx cough and respiratory distress develop.

Diagnosis:

Fertilized ascaris eggs are diagnostic. Unfertilized eggs sink while fertilized eggs float in water. Each egg is oval to round in shape, measuring 75 x 50 micrometers, and has a thick mamillated outer shell and is usually stained brown by bile.

Adult worms are also diagnostic. The worms are long, slender, cylindrical, unsegmented and colored light yellow. The mouth end is surrounded by 3 lips. The male worm is 30 cm long and 4 mm in diameter, and has a curved tail end. A female measures 40 cm ( over a foot long) X 6 mm. The genital aperture is in the upper third of the body and 2/3 of the body contains sacs containing 25 million eggs.

Treatment. Albendazole and Mebendazole are effective in killing the adult worms. A daily dose for 3 days is recommended for cure. Reinfections are common in endemic areas.

Hookworm

Hookworm.

PKGhatak, MD.

The name Hookworm is given to this roundworm because the worm has anchoring teeth or, hard plated in the mouth to latch onto the interstitial wall of its victims. An adult worm is 8 mm long and the female is 11 mm. The worms are round in shape, have a long thin unsegmented body with tapering ends, and are pale creamy color. Each worm carries both sex organs. The outer wall is made of a tough cuticle

Human diseases produced by hookworm:

1. Iron deficiency anemia and protein malnutrition

2. Allergic skin lesions and eosinophilia. Cutaneous larva migrants

3. Eosinophilic enteritis.

The life cycle of hookworm.

Human excreta contaminates the soil where hookworm infection is common. Children playing bare feet on the fields or farmers working on their fields, come in contact with the infective stage of hookworm larva. It takes only 5 minutes for the larvae to find the tiny hair openings and or penetrate the skin. In the dermis, the larvae begin migrating to locate the capillaries or venules and enter. The blood carries the larvae to the right side of the heart and then into the pulmonary alveolar capillaries. This part of the migration takes 10 days, The larvae penetrate into the alveoli and enter the airways. Ultimately, the larvae enter into the major airways and are coughed up and swallowed. In the stomach, they are protected by the outer tough cuticle. Once inside the small intestine, the larva molts twice and develops a buccal capsule with teeth and a muscular esophagus. The larvae attach to the mucous membrane of the intestine from the lower duodenum and upper ilium. The larvae secrete tissue resolving enzymes which dissolve tissue and expose the blood vessels. The larvae bite and remain attached to the blood vessels of the intestine with their teeth or buccal plates. In humans, the parasites do not multiply.

The larvae quickly grow and attain maturity in a month and after mating, begin to release eggs. A female can release 30,000 eggs daily. Adult Nicator worm lives up to 5 years and Ancylostoma species for one year only.

In the soil.

The eggs release the immature Rhabdotiform larvae in a day or two, The larvae feed on the excreta and molt twice. In 7 days rhabdotiform larvae become the infective Filariform larvae. The filariform larva has a short life outside and dies if unable to find a victim within 3 weeks.

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Diagnosis:

The stool test for eggs is commonly done for the diagnosis of hookworm infection. The eggs with multiple larvae are diagnostic. Each egg measures 60 x 40 micrometers. The usual practice is to release the eggs from the fecal matter by placing a portion of the stool sample in a glass jar diluted with water and agitated it thoroughly. The eggs float on the top of the water and are collected by merely touching the top of the water with a glass slide.

PCR tests are available but are hardly utilized.

When the larvae are in migration and until the adult worm starts producing eggs, the stool tests will be negative. The PCR tests are needed for confirmation,

Treatment.

Albendazole is effective and requires a daily dose for 3 days or just one heavy dose.

Iron and vitamin supplements are also required.

Infection of hookworm does not provide protection from future infection. Vaccines are developed but not commercially available.

Epidemiology.

According to a 2010 WHO report, about 120 million people had hookworm infection. The countries where most cases are seen are poor - spanning from Sub Sahara Africa to South Asia, East Asia and the Americas.

Species infective to humans.

Necator americanus infestation is the most common in humans, taking the world as a whole, followed by Ancylostoma duodenale.

Other hookworm species infective to humans are Ancylostoma ceylanicum,

Ancylostoma caninum

Ancylostoma braziliense.

A. barziliense commonly produce eosinophila with creeping skin lesions called Cutaneous larva migrants.

Besides the common mode of infection, some species can infect humans via contaminated drinking water and breast milk in children. Ancylostoma craninum usually remains dormant in the skeletal muscles and produces eosinophilic dermatitis, bronchitis and asthma. Then move to the intestine to propagate.

Amount of blood loss and anemia.

It is reported that each adult Necator worm consumes 0.03 ml of blood and 0.2 ml of blood by Ancylostoma species. In addition, blood is also lost in the stool. On average, in a heavy infestation, humans loose 1 ml of blood per day per adult worm. In general, many dozens of worms live in the intestine at the same time. A heavy infestation is determined by the presence of over 4,000 eggs /gram of feces.

It does not take much time for the children to become severely anemic and the hemoglobin levels fall to 4- 5 grams/dl.

An adult worm lives 1 to 5 years based on the species. An infestation of hookworm does not produce immunity against future infections.

Vaccines are known to protect against fresh infections in people but are not utilized and not produced commercially.

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Lung Flukes

 

Lung Fluke- Paragonimus westermani

                   PKGhatak, MD

Humans are infected by Paragonimus westermani from eating uncooked or poorly cooked crab, crayfish and pork. Metacercariae stage of the parasite travel from the intestine to reach the lungs through the diaphragm. And within a month of reaching the lungs, the worms attend maturity and a pair of adults cross fertilize each other and begin laying eggs in the bronchus. The eggs are coughed up and spat out or swallowed. Eggs hatch in water and newly released miracidia seek out snails. Within the muscles of the snails, the parasites multiply and develop into a motile form of cercariae.  Cercariae leave the snail. Circariae moves along the bottom of rivers or lakes and finds the 2^nd intermediate hosts – crabs, shrimps and crayfish. Again the parasites multiply and develop into infective from metacercariae and are ready to infect humans or any mammals of the cat family.

In East Asia, lung fluke infections are mostly seen, however, the lung fluke infection is prevalent in a wide area of the world, wherever the people eat raw crab meat, or pickled carbs and shrimps and raw crayfish. It is estimated that 200 million people are at risk of lung flue infection.

Symptoms and diseases produced by paragonimus parasites:

Following ingestion, the eggs hatch in the intestine and migrate to the lungs. For 2 days to 2 weeks, during migration of the parasites, the patients have symptoms of abdominal pain and diarrhea. These symptoms are followed by fever, chest pain, cough, rusty sputum production, blood eosinophilia and various forms of infiltrates in the lungs detected by chest x-rays. Occasionally pneumothorax and a small pleural effusion develop.

Weeks later, the main symptoms become chronic cough, with a low grade fever, fatigue and sputum containing traces of blood, resembling pulmonary tuberculosis and or, chronic bronchitis with bacterial infection.

In heavy parasite infection, in 25% of hospitalized patients, the parasites move into the cranial cavity and produce symptoms of meningitis and meningoencephalitis, and seizures. Occipital and temporal lobes are commonly infected. Diplopia to blindness develops. Characteristic soap bubble like pictures are seen within the lateral and occipital ventricles of the brain on CT or MRI of the brain. The CSF examination shows high eosinophil counts.

 Diagnosis.

Sputum examination detected P. westermani eggs, each one measures 80 -120 x 4 – 6 micro M., and are diagnostic. Specific IgM and IgG ELISA tests are also used, specially in CNS infections.

 Treatment:

Praziqyental orally for 3 days is quite effective.

 Anatomy of P.westermani:

The four stages of the parasite are as follows- Eggs, Cercaria, Metacercaria and adult worm.

Eggs – An egg is 80 -120 x 40-60 micro M, brown in color, and resembles a coffee bean. 

Cercaria and Metacercaria are similar in size and appearance to any other Trematode worm,

Adult – the adult worm is 7 -12 mm long and 4 -6 mm wide. The outer wall is covered with scales like spines. It has two suckers like any other Trematodes and each one has both the male and female sex organs. But unlike Liver flukes Lung flukes meet as a pair and cross fertilize each other. Adult worms produce fibrous cavities in the bronchi filled with their excreta and altered blood

Life Cycle of P. westermani.

In general P. westermani needs a snail as an intermediate host but unlike the liver fluke P.westermani requires another host – crabs and crayfish for the multiplication and development to an infective form. P.westermani use any snail species that are locally available, unlike liver flukes.

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Fasciola Hepatica

 

Fasciola hepatica

Liver fluke

PKGhatak, MD

Fasciloa heptica is a flatworm belongs to Trematodes. It infects humans and other ruminant mammals.

Three other species of liver flukes, namely Chonorchis sinensis, Opisthorchis vivirini and Opisthorchis felinecus have similar life cycles and modes of human infection.

In endemic areas, the liver fluke infects the hepatobiliary system and is an important risk factor for Cholangiocarcinoma (CCL). According to the WHO, people in areas of the Mekong River basin, the liver fluke infection is between 30 to 70 % of the population and the death rate from Cholangiocarcinoma is 3 %. CCL is the second most common cause of death in East Asian countries. Thailand has the highest rate of CCL, about 40 in 100,000 people, followed by China, Japan, and other East Asian countries.

The anatomy of Fasciola hepatica.

The adult worm is 3 to 8 cm in length and looks like a leaf. It has a tough outer membrane. The mouth functions as sucker and in addition has an anchoring sucker on its ventral side. It has no inner body cavity, it lives on blood of its victim. Both male and female reproductive systems are present inside the body and a worm usually lives for 9 years inside the bile duct of humans and mammals.

Life cycle:

Each fasciola releases 20,000 to 25,000 eggs daily in the bile. The eggs are plentiful in the stool. The eggs when come in contact with water, transform into embryonated eggs and seek out snails. Inside the snail, the embryos develop into elongated larvae with a long tail. This stage of the parasite is known as Miracidia. Miracidia leave snails and swim by undulating their tails to the nearby vegetation or fish, crabs and crayfish. In this second hosts the larvae transform into cysts are called Metacircarisae. Grazing animals or humans eat contaminated water crest, other vegetation and crustacea and become infected.

In human victims.

The outer wall of the cysts prevents digestion in the stomach and the cysts are propelled into the duodenum. Here the eggs are released. The larvae burrow through the intestinal wall and enter the peritoneal cavity and move to the liver. The worm grows rapidly in the liver and then enters the bile duct system and takes its final residence in the common bile duct or its branches. Within 90 days of entering the human body, the liver flukes become adult worms and begin releasing eggs in the bile.

Diseases produced by Fasciola.

Many people remain symptoms in the early stage of infection. Others develop abdominal pain, nausea and mild malaise within 4 to 7 days when the larvae are migrating from the intestinal wall to the liver. An enlarged, tender liver and abnormal liver enzymes and eosinophilia are usually detected.

This period may last about 7 days and may last for months.

In the chronic stage. Months may pass without any symptoms. Then symptoms of biliary disease begin to occur.  The common symptoms are related to gallstones, Cholangio hepatitis, hepatitis, allergic skin lesions, and the blood eosinophil count is high. are usual symptoms. In heavy infestation of the bile duct obstructive jaundice may occur but usually, a secondary infection is the usual cause of jaundice.

The most serious illness from the liver fluke infection is Cholangiocarcinoma. The bile wall mucosa is damaged by the worm, endothelial metaplasia and fibrosis become recurrent and chronic. This leads to cancer development. Patients seek medical help in a late stage when surgery is not feasible or if performed the results are not good.

Diagnosis:

Examination of stool is a simple test but diagnostic. In very early cases of suspected, asymptomatic infection the saliva, urine and blood tests reveal the presence of Fasciola antigen. Antibody test in 3 weeks post infection becomes positive.

In advanced countries like Japan, Taiwan and others, endoscopy, ERCP and MRI are available to detect parasites in the hepatic and biliary system.

Medical treatment.

Triclabendazole is very effective and requires only two oral doses.

People at risk:

A large population from Malaysia to Japan, China and Russia are at risk of infection of liver fluke infective cysts. Humans are accidental victims due of their life styles or lack of knowledge. The liver of sheep, goat and water buffalos when eaten raw or barely cooked is another source of infection besides drinking water contaminated and other food items already mentioned.

Oriental Sore / Cutaneous Leishmaniasis.

  Cutaneous Leishmaniasis

PKGhatak, MD.

Oriental sore is present in a wide area of the world. The majority of the cases are from the New world countries - Brazil, Bolivia, Peru, Panama, countries around the Mediterranean sea. CL is also prevalent in the Old world countries- the Middle East and Central Africa.

CL is a parasitic disease of the skin and the mucous membranes of the nose, mouth and throat. The parasite is Leishmania which belongs to the Trypanosomastide family and Kenetoplastids order. CT is transmitted to humans by Sandflies.

Incidence of CL.

About 600,000 to 1 million of new cases of CL occur each year. The mortality is few in number and comes from secondary bacterial or, fungal infections but the morbidity is a serious problem.

Anatomy of Leishmania.

Leishmania is an unicellular organism, exists in two different anatomical forms. In the insect vector, leishmania is an oblong flagellated form called Promastigotes reside in the proboscis of the sandfly.. A small round non- flagellated form called Amastigote is ingested by the sandfly from humans during feeding. In the gut of the sandfly, the parasites change to flagellated form.

The nucleus of leishmania is present in the center of the cell; in front of the nucleus in the cytoplasm, a mass of mitochondrial DNA is present called Kinetoplast. From the Kinetoplast a flagellum originates and extends outside. In the cytoplasm, a single stand of mitochondrion and Golgi apparatus are also present.

Leishmania have a unique DNA and glycosomes. It was believed that Leishmania did not propagate by sexual union but recent studies provided contrary evidence that amastigotes exchange nuclear material during binary fission. Leishmania has 34 to 36 chromosomes and during cell division, the chromosomes do not condense.

Life Cycle of Leishmania.

The flagellated Promastigotes infect humans. Sandfly bites introduce the Promastigotes in the human victims. The macrophages, neutrophils and phagocytes engulf the parasite but are unable to break down its surface membrane. Inside the cells, the Promastigotes change into Amastigote. In the macrophages, the amastigotes multiply rapidly to such a number that the cell bursts open and the newly released amastigotes infect other tissues.

Inside the sandfly.

The sandfly takes a blood meal and swallows macrophages loaded with amastigotes, inside the gut the macrophage wall breaks down releasing the amastigotes. Amastigotes transform into Promastigotes and divides and move to proboscis of the sandfly.

 20 different species of leishmania produce CL., and 90 different species of sandflies are the vectors. The important Leishmania species in the old world are L.infuntum, L.donovani, L.major, L.aethiopia. In the New world's species are L.mexicana, L.infuntum, L.guyanensis, L.amazonensis, L.braziliensis and L.panamanensis.

The Phlebotomy sandfly is the vector in old world and Lutzomyia sandfly in the new world. A species of sandfly harbor only certain Leishmania species and that limits one type of CL lesion confined to a local area and absent from adjoining village or locality.

Development of the Skin lesions and Clinical Types.

The sandfly bites on the face, forearms, hands and legs. The bites are painful. A red papule develops at the bite site which turns into a nodule. Several days or weeks later, the nodule ulcerates. This is the beginning of the chronic indolent Oriental sore.

The subsequent healing or progression of CL depends on (a) Leishmania species.(b) victims' immune status- both the innate and acquired immunity. (c) Intercurrent immune diseases. (d) suppressed immunity by drugs which lowers cellular immune functions or delays and diminishes immune globulin synthesis.

Clinical types of CL. (a) Limited Cutaneous Leishmaniasis.(b) Recidivans Leishmaniasis.(c) Mucocutaneous Leishmaniasis. (d) Anergic Diffuse Dermal Leishmaniasis. (e) Post Kala-azar Dermal Leishmaniasis.

Clinical features.

(a) Limited Cutaneous Leishmania. The initial lesion does not progress to ulcers because the victims have good levels of immunity. The lesions heal spontaneously with scars, and patients develop permanent immunity.

(b) Recidivans Leishmaniasis. The initial lesion heals with scars, and months or years may pass without further disease activities. Then new skin lesions begin to appear at or, near the scars. The process goes on for a while, and ultimately the skin lesions heal. Generally, no medication is required.

 (c) Mucocutaneous Leishmaniasis. It is the most devastating form of CL. The initial lesions develop around the nostrils, mouth and eyes. Satellite lesions may develop in the throat. The mucosal lesions produce tissue necrosis and usually penetrate into the deeper layers of tissues and erode the muscles, cartilages and bones. Without medical therapy no recovery is possible. The WHO recommends that all Mucocutaneous Leishmaniasis should be treated and the WHO provides guidance and medications in participating countries.

 (d) Anergic Diffuse Dermal Leishmaniasis. The patients are immune deficient and usually have IHV infection. The initial lesions are papules and nodules but lesions do do ulcerate. Because of the lack of immune cellular response, multiple lesions appear, usually on the face, arms and buttocks. Later, the entire body is covered by several forms of skin lesions – plaques, papule and nodules. The appetence resembles nodular leprosy, however, no nerve damage occurs in this form of leishmaniasis. Treatment with medications is not very effective and where initial success is achieved, the recurrence of new lesions is common.

 (e). Post Kala-azar Dermal Leishmaniasis. Visceral leishmaniasis is better known as Kala-azar. 2 to 20 years after the cure of Kala-azar some patients develop hypopigmented macules, nodules, plaques and erythematous plaques on the face and other areas of the body. The lesions are recurrent and may persist for years.

Diagnosis of CL.

Biopsy. The demonstration of amastigotes within the macrophages is the standard diagnostic method. If there is no blood in the smear and stained with Geismar or Wright stains, a trained person can identify amastigotes without difficulty. An alternative to a biopsy is the aspiration of clear serum from the lesions. This method is equally sensitive. However, in certain forms of CL the parasite numbers are few. So more and more reliance is shifting towards antibody detection by ELISA or antigen DNA detection by PCR test.

Treatment of CL.

The drug treatment is standardized by the WHO and the CDC in the USA. Few cases of CL were detected in the returning veterans from Afghanistan and Syria. In addition to standard therapy, each country has a host of local treatment protocols which are not effective but popular among the locals. Some of them are Cryotherapy, Heat therapy at 40 to 42 degrees C, Paromomycin topical preparations, infiltration of the ulcers with the solution of Sodium Stibogluconate, and urea 10 -15 % solutions. Oral dapsone, Oral Allopurinol and Oral antifungal agents

Standard therapy.

Pentavalent Antimony agents. 

Two commercial preparations are available -Sodium stibogluconate ( Pentostam) and Meglumine Antimonate (Glucantime). Both these two are given intravenously for 10 to 20 days

Liposomal amphotericin B. It is an antifungal drug and is also effective in leishmaniasis but expensive.

Oral Pentostam,

 Oral Miltefosine. It is a wide spectrum antibiotic also effective against Leishmania. Initially, it was approved for cancer therapy.

Various combinations of drug therapy are practiced based on the leishmania species and the degree of tissue damage.

Prognosis.

Mucocutaneous and Anergic diffuse dermal leishmaniasis have poorer prognosis because of destructive facial lesions and disfigurements. Mortality is negligible as such but secondary infection may lead to septicemia and deaths.

Vaccine: No commercial vaccine is produced for Leishmania disease. Russia made a vaccine using attenuated L.major and used in Russian endemic areas with 50 % success in controlling new skin lesions, but the vaccine does not protect against infection from other species than L.major, and also has some troublesome side effects.                           

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Chagas Disease

 

Chagas Disease

American Trypanosomiasis.

PKGhatak,MD.

Chagas disease is named after Dr. Carlos Chagas of Brazil. Trypanosoma cruzi causes Chagas disease in South America and Trypanosoma gambiese causes Sleeping Sickness in Africa. Several species of Leishmania are pathogenic to humans and both Trypanosoma and Leishmania belong to one family.

In 1909, Dr. Chagas investigated an unknown illness that was common in the rural areas of Brazil. He found a blood sucking insect feeding on humans and leaving behind feces and urine near the wound. The excreta of the kissing bug were loaded with the infective form of the parasite. The victims, while sleeping rubbed the feces and contaminated the wound and the parasite also entered the body through the conjunctiva of the eyes.

Trypanosoma cruzi can infect in other ways - Contaminated food and drink by vectors' feces and urine often cause local endemics, contaminated blood transmission and organ transplantation are less common.  Mother to child transmission during pregnancy is a major concern and the children in subsequent pregnancies are also infected.

The victims developed illness in two phases – 1. The initial or the first stage. 2. The chronic stage.

The initial stage.

The initial illness is a mild local inflammation and the regional lymph adenitis and in a few instances only mild systemic symptoms. Occasionally, a furuncle, called Chagoma, develops at the wound site. The illness is self limited. About 50 % of new infections may remain symptom free.

In the 2^nd or Chronic phase.

Years may pass without any signs of illness, and then patients present with symptoms of serious heart, gastrointestinal and neurological diseases.

The parasite Dr. Chagas discovered was a flagellated Protozoa in the blood of the victims. He conclusively proved the pathogenicity of the protozoa by recovering the same organism is susceptible animals. Dr Chagas named the parasite Trypanosoma cruzi to honor his mentor Dr. Cruz.

The Life Cycle of the Protozoa Parasite:

The organism is a motile, unicellular organism having one flagellum. The protozoa have 5 stages of development and two methods of propagation - one by binary fission and the other by sexual union. The different stages of life of the protozoa are named according to the point of attachment of the flagellum to its body or the absence of the flagella. The Greek word for the flagella is mastigot. The infective form that circulates in the blood of the victims is called Trypomastigotes.

Inside the bug.

In the midgut of the insect, the trypomastigotes transform into Epimastigotes, having the flagellum attached to the end of the body. Here epimastogotes multiply, and the epimastogotes enter the hindgut and transform back to Trypanostigotes, And infect humans when the bug takes a bloody meal.

In the victim.

The Trypomastigotes  transform into a round small unicellular organism inside the victims' cells. The parasite has no visible flagella and is called Amastigotes. Amastigotes multiply by binary fission. Amastigotes transform into trypomastigotes and burst open the victim's cells. The released Trypomastigotes infect more tissue, and also enter the bloodstream and lymphatics and are widely distributed in the body. Some of the Trypomastigotes switch back to Amastigotes  divide again and keep on multiplying by binary division. And the cycle repeats again and again.

Besides humans, small animals like monkeys, armadillos and dogs are also infected.

The insect vector. 

The bug that transmits Chagas disease is a Triatomine bug, a variety of Reduviid bug, locally known as the Kissing bug, as they find it on the faces of victims.

There are several species of the Triatomine bug, one species is active in a certain locality or another. The bug is active at night. They come out of cracks of the wall, fall from the ceiling or just crawl on the bed from outside. The bugs bite on the faces of humans (part not covered during cold nights). A recent report says oral route of infection, in recent days, has been the dominant path of infection of Chagas disease.

Chagas Disease:

The incubation period is short.

The initial illness is mild and self limited, and often remains asymptomatic.

The chronic phase of Chagas disease is a protracted severe symptomatic disease of the cardiovascular, gastrointestinal and Neurovascular systems. The mortality rate is high and the disability is severe.

Pathophysiology:

The amastigotes invade muscle cells of the heart and the smooth muscles of the esophagus, and colon and also invade the brain. The inflammatory reactions are mediated by acute phase Cytokines. The initial myocarditis is followed by necrosis of muscles are replaced by fibrous tissues. The cardiac and smooth muscles of the GI tract become weak and flabby. The heart is the most common organ affected by Chagas disease. Cardiac impulse propagation along the His bundle due to fibrosis manifests as heart block, branch block, cardiac arrhythmia and systemic embolism. Massive dilated cardiomegaly and heart failure are the prominent features of this disease. Megaesophagus leads to difficulty in swallowing solid food, and megacolon leads to chronic constipation and abdominal distention and discomfort.

The CNS infection results in strokes and many other neurological manifestations.

Diagnosis:

The mainstay of diagnosis of Chagas disease is the demonstration of moving Trypomastigotes under the coverslip of a thick smear of blood. Under the trained eyes the movement of the transparent parasite around stationary red cells is not difficult. It is a cost-effective test and practical in the rural communities.

Other confirmatory tests and PCR antigen detection and indirect ELISA antibody detection.

Medical treatment:

Two oral medications, Benznidazole and Nifurtimox are effective in killing the parasite but the drugs must be given early in the acute phase of the disease in children 2 to 18 years of age. The older adults develop toxic side effects more frequently and drug therapy is not recommended in adults. Women of reproductive age are tested and treated with drugs to prevent congenital Chagas disease. 

Benznidazole is an imidazole derivate, actives against intracellular parasites. In Chagas disease, the drug is prescribed for 60 consecutive days. The drug inactivates parasitic enzymes and damages DNA and large protein molecules by generating cation radicals. Common side effects of this drug are various GI symptoms, skin rashes peripheral neuritis, thrombocytopenia and leukopenia, and anemia. It is potentially carcinogenic.

Nifurtimox is a nitrofuran drug. The mode of action of Nifurtimox against the parasite is similar to Benznidazole and it generates radicals through its action of nitrogenous enzymes. The adverse reactions are also like Benznidazole. But when prolonged treatment is necessary, Nitrofurans is not suitable because of its adverse effects which are more intense than Benznidazole. Both drugs are contraindicated in pregnancy.

Surgery: 

In the past various types of cardiac surgery were tried to improve function of the failing frail and flabby heart muscles. In the long run, none of those procedures proved to be beneficial and subsequently abandoned. Heart block is effectively treated with cardiac pacemakers. Only cardiac transplantation is a solution is severe heart failure.

Megaesophagus.

Laparoscopic myomectomy, esophageal mucosectomy are less involved procedures. Heller-Pinotti procedure is a more involved operation and is done in early swallowing difficulties. It is a modified Fundoplication operation.

In advanced cases, Thal-Hatakufu operation is done. In this operation, Esophgogastroplasty is performed. The success of the Thal-Hatakufu operation is moderate.

Megacolon.

A Total Colectomy operation is required with anastomosis with -(a) ileorectal, or, (b) ileoanal, or, simply a colostomy.

Prognosis of Chagas disease depends on the stage of the disease. In the early actives phase, the drug treatment is curative.

The survival in the chronic phase is poor.

Incidence and prevention of Chagas disease.

18 million people in 21 countries of Central and South America are infected with Trypanosoma cruzi and 100 million people are at risk of infection.

 Insecticide is used to control the insect vector. Better housing and public education have been successful in bringing down the spread of Chagas disease.

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Dracunculiasis / Guinea Worm Disease

 

Dracunculiasis

Guinea worm Disease

PKGhatak, MD

Guinea worm disease and the name of President Jimmy Crater are intertwined, to recall one, the other name pops up immediately. President Jimmy Carter single highhandedly brought the misery of African people suffering from Guinea worm disease to our consciousness.

Dracunculus medinences, the parasitic nematode (roundworm) has been a curse of humanity known since 1000 BCE. The worm lives a symbiotic life with the water fleas called Copepods which are abundant in the small pools of water in Sub-Saharan Africa. Farmers and others drink water from these pools during hot summer months and ingest Copepods and become infected with the Guineas worm larva.

Life cycle of Drancunculus medinences:

Humans, domesticated dogs, and cattle are victims of the roundworm. Dogs and cattle are infected because of closeness with their masters. People develop incessant burning pain during the release of larvae by the gravid female. Farmers dip their feet in the pool in order to get some relief of the burning sensation. The worm releases thousands of larvae which are food for the Copepods.

Thirsty men drink water from the pool during summer days working in their fields under the hot sun. The outer cuticle of the copepods dissolves by the gastric juices. The released larvae enter the small intestine and begin to move along the tissue planes to the abdominal and thoracic muscles. In about 3 months the worms reach sexual maturity. There, the male and female worms mate and soon the male worm dies. The female starts her migration towards inferior extremities and finally settles underneath the skin of one leg. It takes 12 to 14 months to complete this migration. Once the right moment arises the worm breaks through the skin of the foot or lower leg, forming an ulcer, and continues to deliver larvae for 10 weeks.

The victim suffers burning pain during the entire period. There are no medications to kill the worm or any vaccine to prevent infection. The only solution, as President Carter saw, was to provide people with simple water filters and educate, educate and educate people on how to protect themselves. And he nearly achieved his goal.

Guinea worm diseases:

Nausea, vomiting, and diarrhea following drinking contaminated water are common.

Painful blisters on the legs, leg ulcers, secondary bacterial infection, draining wounds, abscesses, and gangrene of limbs are similar symptoms in all the villagers.

About 1 % fatality from septicemia.

Control of Guinea worm:

This task is a WHO project.

People at risk of Guinea worm infestation:

People living in the countries located in sub-Saharan countries from Angola to South Sudan are at risk.

The success story:

In 1986, 3.5 million people had dracunculiasis and in 2022 only 13 people were found with guinea worm disease. 17 counties out of 21 were free of guinea worm. That is a 99.99 % success rate.

Treatment :

No improvement has taken place over the age old custom of grabbing the worm with a tweezer as breaks the skin. Tie the worm to a small stick and periodically twist the stick with the worm. Slowly and bit by bit the entire I meter long and 1 to 2 mm wide Drancanculia will be out of the leg. But multiple worm infestations is the norm and so the misery of the sufferers continues.

The name Drancunculus is a misnomer, the worm does not drink blood like Dracula or another worm – Hookworm.

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Elephantiasis and Tropical Pulmonary Eosipholia

 

Elephantiasis and Tropical Pulmonary Eosinophila.

PKGhatak,MD

Round worm infestation of people living along the coast of the Bay of Bengal causes  Filariasis. The common nematodes are Wuchereria bancrofti, Brugia malayi,and Brugia tremor. Elephantiasis is the result of Lymphatic channels obstruction by the adult nematodes producing gross deformation of the legs of the victims, resembling elephants' legs. Tropical Pulmonary Eosinophilia is produced by the type I hypersensitive reaction to microfilaria antigen which is released intermittently from the trapped microfilaria in the lung parenchyma.

Life story of the filaria worm:

All the nematodes have a similar life cycle. It consists of 5 stages, part of them in the humans and rest in mosquitoes. A wider variety of mosquitoes - Culex, Anopheles, and Aedes are vectors of human filariasis. The female mosquitoes are infected at the time of feeding on the blood of the infected patients. In the gut and thoracic muscles of the mosquitoes, the microfilaria molt twice and the 3^rd stage larvae are infective microfilariae which move to the salivary apparatus of the mosquitoes and wait for the opportunity to infect humans and carry on to complete two more moltings and take up permanent residence in in the lymphatic channels, lymph nodes, and spleen of victims as adults worms. The male and female worms unite and a female gives birth to thousands of larvae every day. These microfilaria come out at night and circulate in the systemic blood, hoping to be ingested by a mosquito and to continue the life cycle.

Elephantiasis:

120 million people in a wide area of the world, spanning from India, South Asian countries, Western Pacific islands, Tropical Africa, Brazil, Haiti, Dominican Republic and Guyana are at risk of filariasis.

The adult filaria worms preferentially reside in lymph nodes of the groin and neck. The female worms remain fertile for 5 years out of 9 years of their lives. Lymphatic obstruction produces repeated Staphylococcus and fungal infections and scarring. The lymph flow disruption causes the thickening of the skin, and the skin turns hard and lumpy, and the legs become enormous in size. In W. Bancrofti infection the skin of the perineum thickens and causes disfigurement and deformities of the genitalia. The lymph edema that develops from Brugia infection spares the perineum and external genitalia.

Obstruction of the thoracic duct produces bilateral pleural effusion, the fluid is turbid due to the presence of high fat content, specially after a fatty meal. Abdominal pain and Chylous ascites result from abdominal lymphatic obstruction.

Complications: Ulceration and abscess formation, sinus formation from chronic ulcers develop in patients who are not properly cared for. Depression and loss of employment are generally common.

Tropical Pulmonary Eosinophilia (TPE):

Tropical Pulmonary Eosinophilia is much more common in India and in the adjoining countries than Elephantiasis.

TPE is a hypersensitivity eosinophilic inflammation of the respiratory organs. Nocturnal cough, wheezing, fever, loss of weight, blood stained sputum and eosinophilia, at one time thought to be Psudopulmonary eosinophilic tuberculosis. Dr. Weingarten was the first to use the term Tropical Pulmonary Eosinophilia in 1943. The eosinophil count is generally over 3,000/ml. Serum IgE over 1000 mg/dl.

Chest x-ray shows interstitial infiltrates to reticular interstitial pulmonary fibrosis.

Pathology of TPE.

An eosinophils release basic and acidic proteins, Peroxide and neurotoxic chemical in the tissues around the larvae. This weakens the microfilaria and restricts their activities. Complement activation increases opsonization and destruction of microfilaria. The Thymic Lymphocytes type II activation produces IL-4 and IL-5, filaria specific IgM, IgG and IgE and eosinophils. IL -4 potentiates inflammation and Interferon-gamma suppresses inflammation.

Diagnosis of filariasis:

Old standard diagnostic test of direct visualization of microfilaria in the nocturnal blood samples are difficult to exercise and often negative, specially in Elephantiasis. Various methods of concentration of blood for easier detection of microfilaria are practically replaced by the PCR test to detect filarial antigen and indirect ELISA antibodies are more in use at present.

Aspiration of lymph nodes and detecting of microfilaria in the fluid occasionally provide positive results. Also in some cases, microfilaria are detected in ascites and pleural fluids.

Treatment of Elephantiasis:

Adult worms are difficult to remove even by surgery. Ulcerated skin and gross deformed skin segments are removed by surgery.

Treatment of TPE:

In India, where more TPE is seen than Elephantiasis, is customary to use steroids initially for a few days then Diethylcarbamazine is used for 21 days. The results are excellent. Recurrence of TPE is due to reinfection rather than failure of treatment.

Albendazole and Ivermectin are also used but on a limited scale and case by case basis.

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Onchocerciasis

 

Onchocerciasis

PKGhatak,MD.

Onchocerciasis is known as River Blindness. 31 nations in Africa, Yemen and several countries in South and Central America where Onchocerciasis is endemic.

A black fly of Simulium group, is the vector, the worm is Onchocerca volulus and humans are victims and harbor this Nematode worm. In 1915, Dr.Rodolfo Robles found the worm and linked it to eye diseases.

The life cycle of Onchocerca is almost identical to that of Loia loia worm. The areas of exceptions are the vector is black fly, the habitat of black fly is the fast running rivers and the nematode is Onchocerca volulus.

The important difference in the pathogenicity of human illness is that the microfilaria are allergenic to humans, while the adult worms are not. The microfilaria wonders around the body underneath the skin in the subcutaneous tissue and produces several different types of skin lesions. The eye diseases produced by Onchocerca are conjunctivitis, corneal scar, uveitis, glaucoma, macular edema and optic atrophy and blindness. Chronic sclerosing keratitis is the main cause of blindness. Onchocerca is the second most common cause of mass blindness. 17 million people are at risk and 800, 000 have already lost their eyesight.

Onchocerca microfilaria is in symbiotic relation with the bacteria Walachia group. The dying microfilaria releases bacterial antigen that produces sensitization and allergic reaction, and when Ivermectin produces mass killing of microfilaria the overabundance of antigen produces anaphylactic shock and deaths.

WHO has elimination programs for this illness. WHO distributes Ivermectin tablets to the participating nations. And has already eliminated it from several countries in South America, Columbia being the first. Ivermectin kills the microfilaria but not the adult worm, as a result, Ivermectin had to be repeated every 6 to 12 months intervals.

Serological tests and PCR tests are available for diagnosis but visualization of microfilaria in the blood is the mainstay locally.

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Loiasis

 

Loiasis

PKGhatak,MD.

Loiasis is a human parasitic disease produced by a nematode - Loa loa. It belongs to the Filaria group of round worm. Loiasis is endemic in 11 counties of Central and West Africa. In the rainy season, the disease activity is maximum which coincides with the breeding season of Chrysops fly. The fly is a deer fly, locally known as Mango fly or Mangrove fly.

20 million people are at risk of Loiasis and annual incidence is 3 to 10 million. The illness was thought to be benign, now, that is questioned by the finding that the mortality reaches 14 % in local areas where parasitemia is unusually high – over 30,000 microfilaria /ml of blood. Another worm disease, Onchocerciasis, is also endemic in several countries in the very area; and the treatment of Onchocercia by Ivermectin leads to the development of encephalitis and deaths of unsuspected patients having both these two diseases simultaneously.

The first case of Loiasis was reported from San Domingo in 1770, by a French surgeon Mongin who saw the Loa loa worm in the eye of a woman but was unsuccessful in removing it.

The Chrysops fly, is an unusually aggressive and determined fly. It lacerates the skin of its victim with its sharp saw like proboscis and then licks the blood from the wound. The bites are quite painful and attempts to drive the fly away, lead to more bites by the same determined fly who must have a bloody meal for her egg development.

The life cycle of Loa loa:

In the gut of the fly blood containing microfilaria undergoes development to a 3^rd stage of infective microfilaria and in 10 days the microfilaria moves to the proboscis of the fly and is ready to begin its life in humans.

The skin wound and the draining lymph nodes swell and become tender. In 6 months to a year, the worm becomes an adult. The adult worm moves around in the subcutaneous tissue and the sexually mature worms unite and the female worm gives birth to about 20,000 microfilaria every day. The microfilaria move into the pulmonary circulation, and from the lungs, they enter the systemic circulation every day during 10 AM and 3 PM. There they wait for the fly bite and begin their lives inside the fly. Then the cycle repeats. An adult worn can live unto 15 years.

Symptoms produced by the parasite:

Both the adult worm and microfilaria are allergenic to humans.

Most victims, however, are asymptomatic. Generalized itching, urticaria, recurrent muscle and joint pain and tender lumps on the skin over the underlying worm develop. These lumps are common around knees, ankles and other joints and are called Calabar swellings. The migrating adult worm in the subconjunctiva of the eye and eyelids is a characteristic feature of Loiasis and is an Africa Eye Worm Disease. Adult worm in the eyes occasionally enters the vitreous humor of the eye and secondary infection may lead to blindness. The risk of encephalitis when Invective is given is not to be underestimated.

Diagnosis requires visualization of Microfilaria in the blood, collected during daytime and blood smears are stained with Giemsa stain. Serological tests and PCR antigen recognition tests are neither locally available or standardized.

Treatment: Three medications namely, Diethylcarbamazine, Albendazole, Ivermectin are used in the elimination of both the adult worms and microfilaria. The selection of a particular drug based on the the microfilaria load, patient's symptoms and allergic history.

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