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Echinococcosis

Introduction
Causative Agents
Epidemiology
Pathogenesis and Pathology
Clinical Manifestations
Laboratory Diagnosis
Treatment
Prevention and Control
Further Reading

Introduction

Echinococcosis is a zoonotic infection caused by the adult and larval stages (metacestodes) of the Cestode genus Echinococcus (Family Taeniidae). The term Hydatidosis or Hydatid disease is restricted to infection with the metacestode, while Echinococcosis is applied in a general way to both adult and larval infections.

Causative Agents

General description of the parasite

Echinococcus spp. are small tapeworms, rarely more than 7 mm in length. The scolex bears four suckers, and there are two rows of hooks, one small and one lage on the rostellum, the number and length of which may vary according to species. The number of proglottids of the body varies from two to six. The genital pore opens laterally and its position depends on species. The cirrus sac is horizontal or titled anteriorly and the vitellarium is globular

The eggs are ovoid (diameter about 30-40mm) consisting of a hexacanth embryo (oncosphere) surrounded by several envelopes the most noticeable one being the embryophore, which gives the egg a dark striated appearance.

The metacestode basically consists of a bladder with an acellular laminated layer and an inner nucleated terminal layer, which may rise by asexual budding to brood capsules. Protoscolices arise from the inner wall of the brood capsules or from the germinal layer.

Species of the genus Echinococcus

At present four species of the genus Echinococcus are regarded as valid taxonomically. These are Echinococcus granulosus, Echinococcosus multilocularis, Echinococcus oligarthrus and Echinococcus vogeli. These four species are morphologically distinct in both adult and larval stages.

General life cycle

Echinococcus spp. requires two mammalian hosts for completion of their life cycles. Proglottids containing eggs or free eggs are passed in the faeces of the definitive host, a carnivore. The eggs are highly resistant to physical factors and can remain infective for a long period in a suitable environment.

The intermediate host, represented by a wide range of mammals acquires infection by the ingestion of eggs. Following the action of enzymes in the stomach and small intestine, the oncosphere is released from the keratinized embryophore. Bile assists in activation the oncosphere, which penetrates the wall of the small intestine. Penetration is them aided by the hook movement and possibly by secretions of the oncosphere. Upon gaining access to a venule or lacteal, the oncosphere is passively transported to the liver, where some are retained. Others reach the lungs and a few may be transported further to the kidneys, spleen, muscles, brain or other organs.

Once the oncosphere has reached its final location it develops into the metacestode (hydatid larva) stage. Time of development is variable and it may take several months before protoscolices are produced (fertile metacestode). Not all metacestodes produce protoscolices (sterile metacestode). When protoscolices are ingested by a suitable definitive host, following the action of pepsin in the stomach, they evaginate in the upper duodenum in response to a change in pH and exposure to bile. They then develop to the sexually mature tapeworms, approximately four to six weeks after infection, depending on the species and on the susceptibility of the host.

The life cycle of Echinococcus species is complex involving two hosts and a free-living egg stage. The dynamics of transmission of the parasite are determined by the interaction of factors associated with these two hosts and with the external environment. An understanding of these interrelationships and the way in which they influence the dynamics of the system, in particular its stability in the face of perturbation, is central for the planning and assessment of control programme.

The adult worm within the definitive host

The number of worms haboured by dogs is determined primarily by the number of protoscolices ingested. Since asexual reproduction occurs within thee intermediate host, extreme clustering can occur and worm burdens in the thousands are not uncommon. Dogs show a variable degree of natural resistance to infection and there is evidence that weak acquired immunity develops slowly. this immunity may affect both the numbers of worms that establish themselves in the host and their size. The biotic potential of Echinococcus spp. is low. Individual proglottids contain 200-800 eggs and based on the growth rate of the worm it is estimated that one proglottid is shed approximately every 14 days.

Proglottids and eggs in the external environment

Under favourable conditions, detached proglottids may remain active for a few days after being expelled in the faeces. They performed rhythmic contractions and relaxations that assist egg- expulsion and may disperse the proglottids considerable distances from the faecal mass. Since sheep generally avoid grazing areas contaminated by dog gaeces, this dispersal enhances the chances of eggs being ingested. it also has important epidemiological implications because it means that a single heavily infected dog can be responsible for infecting intermediate hosts over a wide area.

Agents responsible for this dispersion have not yet been identified, although a variety of possibilities have been suggested. Wind may account for some movement of eggs, but the observed radial uniformity of the dispersion and the fact that the eggs are intolerant of desiccation suggests that this is not a major dispersion mechanism. An animal agent must, therefore, be suspected. However, birds, flies, beetles and ants would seem to be the most likely to be involved.

Eggs deposited on the apsture are subjected to the microclimate of the environment. They tolerate a wide temperature range. Heat damage does not appear to occur until temperatures reach 380C and the eggs withstand temperature as low as -300C. In contrast, they are very susceptible to desiccation and this factor probably dominates all others in restricting the survival of eggs of Echinococcus spp. in the natural environment. As a principle applying to all taeniids, population of eggs deposited by the definitive host appear to consist of eggs at various stages of maturity

They may mature under suitable conditions. Under favourable conditions mature eggs age and their life span is largely determined by the environmental temperature. This life span may vary from about three days to one year. Within certain limits the longevity of the eggs decreases as the temperature increases. The aging of the eggs is characterized by a gradual loss of the ability of the oncosphere to activate in vitro and this is associated with a progressive decline in infectivity to the intermediate host.

The larval parasities within the intermediate host

The density, infectivity and availability of the eggs in the environment and the feeding behaviour of the intermidiate host together determine the number of infective organisms entering the host B. However, the number of these that become established is strictly controlled by the host regulatory mechanisms. These consist of both a natural and acquired resistance to infection. Natural resistance causes parasite mortality to all stages during development and its extent may be related to the strain, age sex and physiological condition of the host. Little is known of naturally acquired protective immunity in echinococcosis, but assumptions can be made from the extensive studies on other taeniid species. With these, acquired resistance develops after the ingestion of an initial immunizing dose of eggs. This response develops within two weeks of the ingestion of a few as 10-50 eggs, and prevents any further infection. The resistance is maintained throughout the life of the host by the copntinlued ingestion of eggs, but may wane within 6-12 months in the absence of reinfection. Immune mothers may transfer some degree of immunity to their offspring (e.g. via colostrum) but animals do not appear to become fully immunologically competent to cestode infections until several weeks after birth. The rapid development of immunity in competent animals means that the length of time that the intermediate host is susceptible to super-infection following the ingestion of the first eggs, is short (about two weeks). Thus, the events, which occur during this period, determine the larval worm burden for life. This means that grazing management can have a major influence on the level of infection. This immunity also means that the majority of eggs deposited by the definitive host do not initiate infections. Thus, considerable regulation of parasite numbers by the host at this stage.

In common with most host/ parasite systems that have been observed, the hydatid organisms show an over dispersed or aggregated distribution within their hosts. The majority of hosts, therefore, contain only few parasites while a small number contain many. This distribution is generated by heterogenecity in the system and has been shown to have a vital role in determining the dynamics of transmission.

Epidemiology

The perpetuation of echinococcosis disease depends upon the common presence of the parasite, the definitive and intermediate hosts. The continued existence of host and parasite populations depends upon the fine balance of various interacting regulatory forces. The ability of the populations to survive perturbation, in the form of, for example, environmental change, without either becoming extinct or reaching plague proportions is termed stability. Theoretical work on the dynamics o host/parasite systems has indicated that such characteristics as overdispersion of parasite numbers within the host population and the development of host immunity act as important stabilizing influences. Recently it has been recognized as global public health problem. It has been found in all sheep raising countries including India. The highest prevalence is reported in Andhra Pradesh and Tamil Nadu.

Pathogenesis and Pathology

Cystic Hydatid Disease - (Echinococcus granulosus)

After their ingestion, cestode eggs hatch to release embryos in the small intestine. Penetration through the mucosa leads to blood-borne distribution to the liver and other sites, in which development of the hydatid cyst begins. Although most primary infections in humans consist of a single cyst. 20 to 40% of patients have multiple cysts or multiple organ involvement. The liver is the most common site for hydatid cysts (50 to 70%), followed by the lungs (25%) and, less frequently the spleen, kidneys, heart, bones, central nervous system, and elsewhere. The fully developed hydatid cyst is filled with fluid and typically unilocular; however, multilocular or chambered cysts are not uncommon. Structurally, the cyst consists of an inner germinative layer of cells supported by an acellular laminated membrane of mucopolysaccharide material (endocyst). Small secondary cysts, called brood capsules, develop internally from the germinative layer and produce multiple protoscolices by asexual budding. A protoscolex is a scolex in which the rostellum and suckers are deeply withdrawn into the post-sucker region. Surrounding the hydatid cyst is connective tissue adventitial reaction of variable intensity (ectocyst.)

Growth is by concentric enlargement. Rates of growth of hydtid cysts are highly variable and range from 1 to 5 cm in diameter per year. The slowly growing hydatid cyst is often well tolerated until if causes dysfunction because of its size. In humans the cyst may attain a volume of many liters and contain many thousands of protoscolices. Rupture or leakage of cysts may precipitate allergic reactions as a consequence of sensitization to echinococcal antigens. At the same time, seeding of the peritoneum or pleura with protoscolices may result in extensive seconday cyst formation

Alveolar Hydatid Disease - (Echinococcus inultiloculoris)

Compared with E. granulosus, larval E. multilocularis is more progressive and damaging to the host. Human disease caused by E. multilocularis has many of the characteristics of malignant neoplasia. Growth in humans is different from that in natural rodent hosts in that the larval mass is inhibited from completing its development and remains in the proliferative stage indefinitely, it then continues to invade and destroy the hepatic parenchyma, and retrogressive stages within the mass result in necrosis of the central portion. Macroscopically the hepatic lesion usually appears as one or more firm to solid, whitish, rounded masses slightly elevated above the surrounding tissue of the surface of the liver. When transected, it appears to consist of a central cavity surrounded by dense, pale tissue that lacks a clearly defined border with respect to the adjacent hepatic tissue. In advanced cases the cavity usually contains turbid yellowish to brown fluid with particles or fragments of necrotic tissue. Microscopically, cysts of various sizes are scattered or closely aggregated in a matrix of connective tissue. Only rarely are brood capsules and calcalreous corpuscles present. Metastasis by a hematogenous route is not uncommon, and secondary foci usually occur in the brain and lungs.

Clinical Manifestations

Cystic Hydatid Disease

Clinical manifestations of cystic hydatid disease may be absent or result from the mass effect and anatomic position of the slowly growing cyst(s). The interval between first infection and clinical manifestations is variable and often prolonged for many years. Most infections are diagnosed in patients between 10 and 50 years of age. The signs and symptoms of hepatic hydatid disease may include hepatic enlargement (with or without a palpable mass in the right upper quadrant), right epigastric pain, nausea and vomiting. Rupture or leakage usually results in acute or intermittent allergic manifestations. Complications that may exist at the time of initial presentation include traumatic or spontaneous rupture, thoracobilia and biliarv fistula. Twenty five percent of patients with hepatic cysts also have cysts in their lungs.

Leakage or rupture of hydatid cysts in the lungs causes chest pain, coughing, dyspnea and hemoptysis. Hydatid membranes may be expectorated, sometimes resulting in spontaneous cure. Emergency complications that may exist at the time of presentation include cyst rupture and secondary bacterial infection. Nearly 40% of patients with pulmonary hydatidosis have liver involvement as well.

The first symptom of cerebral cysts may be raised intracranial pressure or focal epilepsy, whereas kidney cysts may be manifested by loin pain or hematuria. Bone cysts are often asymptomatic until pathologic fractures occur, and, because of their resemblance, they are often misdiagnosed as tuberculosis lesions.

Alveolar Hydatid Disease

The insidious and progressive nature of alveolar hydatid disease usually results in delayed onset of symptoms and diagnosis, by which time the lesions have invaded extensively or metastasized and are inoperable. The clinical signs of the disease usually do not become evident until middle age. Initial symptoms are generally vague. Mild upper quadrant and epigastric pain with hepatomegaly may progress to obstructive jaundice. Occasionally the initial manifestations are caused by metastases in the lungs or brain. Patients eventually succumb to hepatic failure or invasion of contiguous structures. The proportions of surgically resectable cases have varied from 20 to 60°. Of the nonresectable cases, 90% of patients died within 10 years.

Laboratory Diagnosis

The diversity of clinical manifestations and the difficulty of demonstrating the deeply located cysts often make diagnosis very difficult. Hydatid disease usually comes to the attention of the clinician for four major reasons: when a large cyst has some mechanical effect on body function; when allergic phenomena or other symptoms such as eosinophilia occur; following the accidental traumatic rupture of a cyst with consequent acute allergic reactions; and on the incidental finding cysts during roentgenography, body scanning or surgery for other clinical reasons. Other methods are Radiological methods, Immunodiagnosis and examination of the cyst fluid.

Treatment

Cystic Hydatid Disease

Although the disease may not progress or may resolve spontaneously, the risks of anaphylactic reactions, dissemination following rupture, and relentless growth, which renders subsequent therapy more difficult or impossible provides a strong argument for early therapy.

Surgical extirpation of the hydatid cyst remains the most effective treatment. Extirpation is usually accomplished by using generous surgical exposure and aspiration of part of the cyst contents, followed by injection of a protoscolicidal agent (hypertonic saline or silver nitrate) and complete removal of the endocyst. The residual cavity is then treated by suture plication, marsupialization, closure after filling with saline, or omentoplasty. An alternative method of removal is en bloc excision, a procedure particularly applicable to splenic cysts and, to a lesser extent, to hepatic lobectomy. Diagnosis and surgical removal of intact cysts before the onset of complications result in high cure rates with low surgical mortality (1 to 4%). In contrast, secondary or recurrent disease often requires repeated surgical intervention, with mortality reaching 20%.

Until recently, there has been little to offer patients with anatomically inesectable lesions e.g.those in whom the spine is involved or in whom spontaneous rupture, operative spillage, or wide spread metastatic cyst formation has occurred. Under such conditions, treatment with mebendazole or albendazole may be attempted, although the results are unpredictable and adverse reactions have been reported and liver cysts of E. granulosus appear to respond relatively well, but cysts in other locations, particularly in the brain, bone, and eye, respond poorly if at all. Mebendazole (50 mg to 150 mg/kg of body weight per day, as a single oral dose for 3 months) or albendazole (10 to 15 mg/kg per day, in divided oral doses for 1 month) are recommended for small sized cyst situated in inoperable sites; many patients require repeated courses. Albendazole is also recommended for prevention of accidental cyst rupture with spillage of contents. Reported side effects have included neutropenia, liver toxicity, and hair loss. As long-term prognosis in individual patients is difficult to predict, prolonged follow-up is required to determine the eventual outcome of treated cases.

Alveolar Hydatid Disease

Resection of the entire larval mass is the aim of surgery for this otherwise progressive and fatal disease. Usually the entire affected lobe(s) must be removed. When involvement is more extensive wedge resections of the lesions may be attempted. Because alveolar hydatid disease is often not diagnosed until parasitic invasion is well advanced, the lesion is frequently not resectable; thus partial resections and biliodigestive and hepatodigestive anastomoses are performed as palliative measures, predominantly to ensure bile passage. For treatment of nonresectable cases, continuous mebendazole therapy (40 mg/kg of body weight per day) results in clinical improvement and prolonged survival time: however the effect is inhibitory rather than lethal to the parasite. Recent reports on therapy with albendazole suggest similar effectiveness.

Prevention and Control

It is evident that the stability of the host/parasite system determines to a major extent the effort required for the control of Echinococcosis. Evidence from the several control programmes against echinococcosis indicate that the stability of this system is quite fragile. This is a contrast to similar or concurrent programmes against other taeniid tapeworms. It would seem that although these parasites have similar life cycles, important differences exist that markedly influence their stability. These differences may include the low egg production of Echinococcus spp. and the occurrence of asexual reproduction within the intermediate host.

Cystic Hvdatid Disease

For individual in endemic areas, preventive measures include careful personal hygiene, strict dietary regulation of pet dogs to preclude ingestion of sheep offal, and avoidance of dogs that are not so regulated. Prophylactic treatment of dogs with praziquantel at intervals just short of the prepatent period (e.g. 45 to 50 days) prevents egg excretion in dogs so treated.

The principal objective of control of cystic hydatid disease is reducing parasite prevalence in definitive and intermediate hosts to levels below those necessary for continued transmission. Measures that have been used in various circumstances include health education, control of livestock slaughtering in abattoirs and on farms, safe disposal of infected viscera, dog control, and periodic diagnostic testing and mass treatment of dogs with praziquantel.

Alveolar Hydatid Disease

Personal preventive measures include avoidance of contact with foxes and other potentially infected final hosts. Control of pet dogs and cats that are liable to eat infected rodents can he prevented by monthly prophylactic treatments with praziquantel (5 mg/kg of body weight). Potentially exposed human populations should be educated about the dangers of the disease to promote better personal hygiene and sanitation and to motivate them to take effective measures to prevent their pets from eating rodents.

Echinococcosis

Echinococcosis

Introduction

Causative Agents

Epidemiology

Pathogenesis and Pathology

Clinical Manifestations

Laboratory Diagnosis

Treatment

Prevention and Control

Further Reading