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Parasitic Liver Disease
Abbreviations
ALA
amebic liver abscess
CAA
circulating anodic antigen
CCA
circulating cathodic antigen
CIE
counterimmunoelectrophoresis
EDHS
Egypt Demographic and Health Survey
ELISA
enzyme-linked immunosorbent assay
ERCP
endoscopic retrograde cholangiopancreatography
GASP
gut-associated schistosome proteoglycan
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IFA
indirect immunofluorescence assay
IHA
indirect hemagglutination
PAIR
puncture, aspiration, injection, reaspiration
PCR
polymerase chain reaction
PPF
periportal fibrosis
PZQ
praziquantel
T H 1
T helper 1 cell
T H 2
T helper 2 cell
WHO
World Health Organization
Introduction
Parasitic diseases continue to be a major cause of morbidity and mortality, with more than 3 billion people infected worldwide, especially in the developing world, where improved measures to prevent infection require considerable investments in the public health infrastructure.
Liver parasites span a wide range of complexity, and different species mature and reproduce within hepatocytes, reticuloendothelial cells, the portal venous system, and the bile ducts. Successful well-adapted parasites can accommodate the immune responses of normal hosts and cause minimal acute injury as they generate enormous numbers of progeny with the potential to infect other hosts, whereas hosts with abnormal or compromised responses are at risk for severe disease manifestations. Long-lived parasites such as helminths are more remarkable for their ability to down-regulate host immunity to protect them from elimination and minimize severe pathology in the host. Helminths that infect the liver and hepatobiliary system include nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms or flukes). The infection is often chronic and can cause insidious or frank disease that leads to considerable morbidity; however, the risk for mortality is low. The majority of morbidity and mortality from these infestations is caused by the host immune response to the larvae or adult worm. They establish numerous strategies and diverse molecular mechanisms for evading host immunity that can promote persistence and facilitate their establishment, growth, and reproduction, in addition to chronicity factors that favor completion of the life cycle inside an immunologically hostile environment and transmission of parasites. The generation of protective immunity to helminth parasites is critically dependent on the development of a CD4 + T helper type 2 (T H 2) cytokine response ( Fig. 39-1 ). Helminth products appear to be inherently adjuvantized in that they can promote strong T H 2 responses to themselves and to bystander antigens in the absence of any additional adjuvant. Dendritic cells, the primary interface between infection and induction of adaptive immune responses, play a central role in the modulation of helper T cells with the initiation of T H 2 responses through the production of cytokines and expression of certain surface molecules. Furthermore, host-parasite interactions specifically involve interactions between helminth excretory/secretory products and host toll-like receptors and lectins, and the putative functions of helminth proteases in activating and recruiting innate immune cells. The development of adaptive antiparasitic T H 2 cytokine responses may prevent strong immune responses against parasitic worms, thereby allowing their long-term survival and restricting pathology. Interestingly, both parasitic infections and cancer have complex natural histories and long latent periods during which numerous exogenous and endogenous factors interact to conceal causality. Although only urinary bladder carcinoma and cholangiocarcinoma have been definitely known to develop as a result of Schistosoma haematobium and the hepatobiliary parasites ( Clonorchis sinensis, Opisthorchis viverrini , and Opisthorchis felineus ), respectively, other parasites have been implicated in facilitating malignant transformation through chronic inflammation, modulation of the host immune system, disruption of proliferation-antiproliferation pathways, induction of genomic instability, and stimulation of malignant stem cell progeny. Liver parasites can either affect the liver parenchyma itself, such as schistosomiasis, hydatid liver disease, or amebiasis, or have a hepatobiliary effect and affect both the liver and the biliary system, such as fascioliasis, clonorchiasis, and opisthorchiasis.
Stool studies, radiologic imaging, and serologic testing are the mainstays in diagnosis. However, having a high index of suspicion is a critical step in the diagnosis and management of patients with hepatic helminthiasis. Researchers and clinicians alike are moving forward with chemoprophylactic and vaccine preventive strategies in an effort to decrease the morbidity and mortality caused by helminthic infestation worldwide.
Schistosomiasis
Schistosomiasis is a multifactorial disease caused by the trematode Schistosoma that involves environmental, behavioral, parasitic, vector, and host factors. It continues to be a significant cause of morbidity and mortality worldwide and the second leading parasitic disease after malaria. There are seven schistosomal species with different geographic distribution ( Table 39-1 ). Approximately 230 to 300 million people are affected by schistosomiasis in 74 countries worldwide, with a high concentration in Asia, Africa, and South America ; annual deaths are reported to total 280,000. The Nile River has been an epicenter for schistosomiasis since ancient Egypt. In 1980, an estimated 10% of the 200 million persons infected with Schistosoma were Egyptians. Two species of Schistosoma — S. haematobium , which primarily causes disease in the urinary tract, and S. mansoni , which principally causes morbidity in the gut and liver—are endemic in Egypt. Since the 1960s, S. mansoni increased in prevalence in the Nile Delta whereas S. hematobium shifted its prevalence to be higher in Upper Egypt. This was mostly related to change in water kinetics after the construction of the Egyptian Aswan High Dam. This was not accompanied with change in overall prevalence of schistosomiasis.
TABLE 39-1
Schistosoma Species and Their Geographic Distribution
| Schistosoma Name | First Intermediate Host | Endemic Area |
|---|---|---|
| S. guineensis | Bulinus forskalii | West Africa |
| S. intercalatum | Bulinus spp. | Africa |
| S. haematobium | Bulinus spp. | Africa, Middle East |
| S. japonicum | Oncomelania spp. | China, East Asia, Philippines |
| S. malayensis | Not known | South East Asia |
| S. mansoni | Biomphalaria spp. | Africa, South America, Middle East |
| S. mekongi | Neotricula aperta | South East Asia |
Infection takes place when the free-swimming larval forms of the parasite, known as cercariae , are shed into fresh water by the snail intermediate host and enter the body by penetration of the skin. Larvae migrate to the portal venous system; sexual reproduction occurs in the portal vein, where adult worms reside and eggs are laid. Eggs pass from blood vessels into tissues, including intestinal or bladder mucosa, from which they are shed in feces or urine. Hepatic schistosomiasis results from the host's granulomatous cell–mediated immune response to the soluble egg antigen of S. mansoni , which eventually progresses to irreversible fibrosis and, consequently, severe portal hypertension. Eggs remain viable in the liver for approximately 3 weeks. The eggs cause a primarily T H 1 immune response with later recruitment of eosinophils and granuloma formation. Granuloma formation ( Fig. 39-2 ) is a helper T cell–mediated delayed hypersensitivity reaction driven by T H 2 cytokines such as interleukin-4 (IL-4) and IL-13, whereas IL-10, interferon-γ, and a subset of regulatory T cells can limit the schistosome-induced pathology. In addition, a variety of cell types have also been implicated, including hepatic stellate cells, activated macrophages, and regulatory T cells. The balance between T H 1- and T H 2-type cytokines influences the extent of the pathology and the development of fibrosis. Eggs are detectable inside the granulomas with the subsequent formation of marked portal and perilobular fibrosis, which is most pronounced with S. mansoni and S. japonicum . The final result of hepatic schistosomiasis with a heavy S. mansoni burden is severe portal fibrosis and greatly enlarged fibrotic portal tracts, which resemble clay pipestems thrust through the liver (termed Symmers pipestem fibrosis ). Interestingly, normal liver architecture is preserved, lobular architecture is retained, nodular regenerative hyperplasia is not observed, and thus the fibrosis could be reversible, at least in part.
Coinfection with viral hepatitis, either hepatitis B virus (HBV) or hepatitis C virus (HCV), is very common because the regions with a high prevalence of schistosomiasis usually have a high endemicity of chronic viral hepatitis as well. In schistosomiasis populations, HCV infection rates range from 1% in Ethiopia up to 50% in Egypt. Egypt is endemic for both S. mansoni and S. haematobium , with community prevalence often ranging between 15% and 45%, in addition to having the highest worldwide prevalence of HCV, with an estimated 8 to 10 million in a population of 68 million exposed to the virus and 5 to 7 million with active infection. An important cause of the high exposure to HCV was the establishment of a large reservoir of infection as a result of extensive schistosomiasis control programs that used intravenously administered tartar emetic 20 to 50 years ago. In 2008, the Egypt Demographic and Health Survey (EDHS) conducted on behalf of the Ministry of Health revealed that an overall 15% of EDHS respondents had HCV antibodies in their blood, thus indicating that they had been exposed to the virus at some point, whereas 10% were found to have an active infection with higher levels of infection in older cohorts because of their exposure to the schistosomiasis treatment programs during the 1960s to 1980s. The association between both schistosomiasis and HCV is known to cause earlier liver deterioration and more severe illness. The liver is the principal site for both HCV replication and egg deposition, which down-regulates the local immune responses in the liver and results in suppression of the intrahepatic bystander immune response to HCV. This may also occur during inactive schistosomal infection, as the ova remain in the hepatic portal tracts and their soluble antigens could influence the host's cell-mediated immunity for a considerable time. Coinfection can also produce a unique clinical, virologic, and histologic pattern manifested by viral persistence with high HCV RNA titers, higher necroinflammatory and fibrosis scores in liver biopsy specimens in addition to poor response to interferon therapy, and accelerated progression of hepatic fibrosis. A recent study showed that positive schistosomal serology had no effect on fibrosis staging, whereas it was significantly associated with failure of response to HCV treatment even if antischistosomal therapy was taken.
Clinical Manifestations
The clinical manifestations of schistosomiasis can pass through acute, sub acute and chronic stages. These stages correlate with the immune response to infection. Sixty percent of infected patients can be symptomatic, whereas 10% only have serious disease that necessitates medical advice. The disease has an incubation period of between 4 weeks and 6 weeks. A maculopapular eruption may arise at the site of skin penetration by the cercarial form of the parasite in the early stage. A potentially fatal, acute form of schistosomiasis that is common in areas with high transmission rates, termed Katayama fever, may occur. It is manifested by fever, chills, headaches, arthralgia, epigastric pain, diarrhea with blood-flecked mucus, loss of weight, lymphadenopathy, and urticarial skin reactions. The liver and the spleen are moderately enlarged, especially in the case of S. japonicum and S. mansoni infection. In chronic schistosomiasis, advanced hepatic disease is characterized by signs and symptoms related to the portal fibrosis and the presinusoidal portal hypertension: esophageal and gastric variceal bleeding and splenomegaly with preserved hepatocellular synthetic function until the last stage of the disease. Growth retardation and late development are specifically associated with schistosomiasis in heavily infected children. When present, laboratory evidence may include peripheral eosinophilia, anemia, hypoalbuminemia, and hypergammaglobulinemia, in addition to pancytopenia because of splenic sequestration. A syndrome caused by chronic persistent infection with one of the Salmonella species has been described in association with schistosomal infection. It is characterized by a long history of an indolent febrile illness and bacteremia, as well as hepatosplenomegaly, edema, and lower limb petechial rash.
Diagnosis
Identification of Schistosoma ova in excreta or in mucosal biopsy specimens is the most appropriate method for diagnosis of schistosomal infection, to determine whether an indication for chemotherapy is present, for evaluation of antischistosomal drugs, and for monitoring in epidemiologic surveys. No single stool examination procedure is totally reliable; sensitivity varies between 50% and 80%, depending on the patient's intensity of infection, the number of eggs in the sample examined, and the care taken by the examiner. In addition, the examiner must wait at least 2 months after the last known freshwater contact before examining for eggs, as a latent infection takes this long period to start producing eggs. Multiple (three to four) specimens should be examined, and sedimentation, filtration, and centrifugation procedures are better than floatation because schistosome eggs are relatively heavy. The Kato-Katz technique, a semiquantitative stool examination technique, is the standard method recommended by the World Health Organization (WHO) for the field diagnosis of intestinal schistosomiasis and is generally recommended for the diagnosis and evaluation of S. mansoni infection by schistosome experts. However, concern that this technique has low diagnostic sensitivity is increasing. Rectal biopsy is considered the most sensitive technique and is valuable when stool examination is negative in patients with light and partially treated infections. The miracidium hatching test is a Chinese test applied by public health workers to rule out S. japonicum infection. First, eggs are concentrated (through placing feces in a nylon tissue bag put in distilled water) then examined macroscopically for hatching of miracidia that indicate presence of infection.
Some of the laboratory parameters may be related to portal hypertension. In endemic areas, thrombocytopenia proved to be a good sensitive test to detect hepatosplenic schistosomiasis and can be used as a basic screening tool for such patients. A recent study showed a significant difference in the mean platelet counts between patients with and without hepatosplenic schistosomiasis. At ROC curve of platelet count of less than 143,000/mm 3 , the sensitivity exceeded 92% in all groups, whereas the specificity ranged between 44.4% and 75%. Serologic tests have many disadvantages in that they become positive too late after infection, become negative too late after cure, can cross-react with other infections (e.g., fascioliasis), and are unrelated to the intensity of infection. However, they are useful when parasitologic tests are negative, in nonendemic situations, and in epidemiologic surveys, especially in eradicated controlled areas where prevalence is expected to be low. Indirect hemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) are the most commonly used methods, but other techniques, including complement fixation, flocculation, indirect fluorescent antibody testing, and radioimmunoassay, have highly variable sensitivity and specificity because of the wide range of types and purity of schistosome antigens used, in addition to lack of standardization. More recently, a novel rapid dipstick with latex immunochromatographic assay (DLIA) has been developed to detect anti- Schistosoma japonicum antibodies in human serum. The sensitivity and specificity of DLIA were considerably high (95.10% and 94.91%, respectively). This test could be easily delivered anywhere with a beneficial rapid diagnosis and large scale field applications.
Schistosomal antigen detection tests can alternatively be used because they measure parasite-derived substances and therefore would be more comparable with the worm burden and more indicative of active infection. The best studied antigens are the secretory-excretory antigens of the adult worm, also known as gut-associated antigens ; the circulating anodic antigen (CAA), also known as gut-associated schistosome proteoglycan (GASP) ; and the circulating cathodic antigen (CCA), also known as M antigen . An ELISA test for another circulating antigen derived from S. mansoni , soluble egg antigen, had a sensitivity of 91% in serum and 97% in urine. A dipstick assay that detects CCA in the urine of S. mansoni –infected patients with 92% sensitivity has been of great value in monitoring large-scale interventions such as chemotherapy and vaccination programs. Using reverse vaccinology techniques, a scientific group cloned and expressed a recombinant form of Sm200 C-terminal (1069-1520) region. This ELISA test represented an important tool to be used in the diagnosis of schistosomiasis.
In addition, polymerase chain reaction (PCR), which can detect S. mansoni DNA in human serum and feces, yielded high sensitivity because it can detect fecal egg counts as low as 2 to 4 eggs/g, with no cross-reaction with other helminthic infections. Another novel diagnostic strategy was developed, following the rationale that Schistosoma DNA may be released in blood as a result of parasite turnover and reaches the blood. Cell-free parasite DNA (CFPD) can be detected in plasma by PCR for any stage of the disease.
Schistosoma miRNAs may be involved in the pathologic processes of schistosomiasis. Recent studies suggested that schistosome-specific miRNAs (such as Bantam and miR-3479-3p) could be used as biomarkers for schistosomiasis diagnosis. In addition, aberrant miRNAs can be produced by a host in response to schistosomal infection, and may subsequently contribute to the pathogenesis of schistosomiasis-associated hepatic injury. To date, 79 mature miRNAs in S. japonicum and 225 mature miRNAs in S. mansoni are documented in miRBase (Version 21).
Ultrasonography (US) is a well-established tool for the diagnosis and grading of hepatic periportal fibrosis (PPF), a major pathologic consequence of S. mansoni infection and a hallmark in its diagnosis. The typical “bull's-eye” appearance on US is characteristic and represents an anechoic portal vein surrounded by an echogenic mantle of fibrous tissue. A US grading system for hepatic PPF in patients with pure schistosomiasis that involves the thickness of portal tracts has been proposed: grade I, 3 to 5 mm; grade II, 5 to 7 mm; and grade III, greater than 7 mm ( Fig. 39-3 ). This score provides a simple, inexpensive, accurate, noninvasive means of screening individuals with hepatosplenic schistosomiasis for esophageal varices. This score strongly correlates with previous gastrointestinal hemorrhage and thus accurately reflects the hemodynamic changes and provides a good estimate of the clinical status of patients. However, the finding of PPF by sonographic examination has been questioned when magnetic resonance imaging (MRI) was used to confirm the diagnosis of hepatic PPF. A significant number of patients in whom PPF was diagnosed by US were shown by MRI to have fat infiltration of the periportal tracts. Thus a more accurate clinical diagnosis of hepatosplenic S. mansoni could be based on the information obtained by clinical, US, and MRI examination (whenever possible).
Another related issue regarding imaging and schistosomiasis is the effect of hepatic schistosomal affection on proper assessment of liver fibrosis status using transient elastography (fibroscan). In a study for the role of fibroscan in HCV infected patients, positive schistosomal serology status led to a statistically significant disagreement between the results of liver biopsy (Metavir) and the fibroscan results. This was more elucidated in F2 and F3 fibrosis stages. The sensitivity of fibroscan for the detection of the F2 fibrosis stage decreased from 64% among negative schistosomal serology patients to 30.8% among positive schistosomal serology patients. Similarly, sensitivity to detect F3 stage decreased from 43.8% to 21.4%.
Treatment
Schistosomal infections can be cured with inexpensive drugs, but people living in endemic countries usually become reinfected. The first effective therapy for schistosomiasis, in which multiple intravenous injections of tartar emetic were used, was introduced in 1918 and remained the standard therapy for S. mansoni and S. japonicum infection for more than 60 years. Three effective schistosomicidal drugs are now in use: metrifonate (for S. haematobium ), oxamniquine (for S. mansoni ), and praziquantel (PZQ) (for all human species).
Praziquantel
Praziquantel is an isoquinoline compound that is used to treat human schistosomiasis on a large scale. It is a safe, nontoxic drug that is given orally in a single dose of 40 mg/kg of body weight and is highly effective against all human schistosomes, with cure rates of 80% to 90%. PZQ produces instantaneous contraction of the muscles of the parasite, followed by spastic paralysis of the worm, which is swept to the liver for phagocytosis; thus the host's immune response appears to be strongly implicated in the mode of action of PZQ. Minor side effects may occur in the form of epigastric discomfort, abdominal colic, nausea, vomiting, headache, dizziness, pruritus, and transient skin eruptions. An impending danger with serious implications for the health protection of millions of people infested with schistosomiasis is the development of drug resistance, which has occurred in Brazil and Kenya. Cure rates have decreased in the last decade and were found to be very low in Senegal because of drug resistance. This concern is reflected by the recent proposal of a new class of compounds that could represent a novel source of drugs against schistosomiasis. Another problem with PZQ is that it does not kill schistosomula that are between 3 and 12 days old.
New Drugs
Mirazid is an herbal drug derived from myrrh (purified Commiphora molmol Engler) that was developed in Egypt. The drug was found to be safe with no serious side effects. However, its efficacy has been debated; some studies showed high efficacy in the treatment of schistosomiasis and fascioliasis, with a cure rate of 91.7%, whereas other authors have found it to have a much lower cure rate than PZQ in their studies. Therefore Botros and colleagues did not recommend mirazid as an agent to control schistosomiasis.
Artemether (an antimalarial drug) can kill these organisms and can prevent new infection with a dose given every 2 weeks, but it should not be used in malaria-endemic areas to prevent the selection of artemether-resistant Plasmodium falciparum . Artemether has been tried in S. japonicum –endemic areas in southern China to prevent new infections ; it was found to be active against other human schistosomes and appears to be synergistic to PZQ in killing adult worms.
Control
In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation arranged a meeting entitled Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals . This meeting focused on the potential role of schistosomiasis vaccines and other tools for schistosomiasis control and elimination strategies. Although schistosomiasis elimination in certain focal areas may be achieved by current mass drug administration (MDA) programs, global control and elimination will require an integrated approach with other different interventions such as snail control, environmental sanitation and modification (water, sanitation and hygiene) and more future innovative tools (such as vaccines).
Ultimately, prevention and control programs of schistosomiasis should be multifaceted; that is, they should include chemotherapy, reduction of water contact and contamination, snail control, and vaccination. More than 10 important antigens with strong potential as vaccines candidates were developed; however, most of them have been difficult to move forward. A recombinant antigen vaccine against S. mansoni remains elusive, in part because the parasite deploys complex defensive and offensive strategies to combat immune attack. The most potent candidates are egg antigens and the schistosomular tegument membrane antigens (Sm 23, SmTSP-2, and Sm29). A newer chimeric form (Sm-TSP-2/5B) provided significant reductions in adult worm and liver egg burdens. Another recently identified and promising antigen is Sm 14. This protein provokes protection against S. mansoni and proves to be a viable and stable vaccine candidate for further clinical testing. Concerning the tegumental protein Sm29 of Schistosoma mansoni , it was considered as a promising antigen to compose an anti-schistosomiasis vaccine. However, recombinant Sm29 is expressed in Escherichia coli as insoluble inclusion bodies and requires an efficient process of refolding for efficient production. A recent study succeeded in refolding it with a high yield (73%) as a stably soluble and structured protein. This refolded antigen provided a protective effect against S. mansoni development in immunized mice. A successful vaccine will probably require a cocktail of antigens rather than a single recombinant protein.
Echinococcosis ( Echinococcus granulosus and Echinococcus multilocularis )
Introduction
The most important zoonotic Echinococcus species, from a public health standpoint, are E. granulosus and related species that cause cystic echinococcosis and E. multilocularis , the cause of alveolar echinococcosis. The WHO has included both echinococcosis and cysticercosis as part of a neglected zoonosis subgroup for its 2008 to 2015 strategic plans for the control of neglected tropical diseases. Geographically distinct strains of E. granulosus exist with different host affinities. Molecular studies using mitochondrial DNA sequences have identified 10 distinct genetic types (G1 to G10) within E. granulosus . The sheep strain (G1) is the most cosmopolitan form and is the one most commonly associated with human infection.
Immune Response
A combined T H 1 and T H 2 cytokine profile appears to be crucial for prolonged parasitic growth and survival. T H 1 cytokines promote the initial cell recruitment around the parasite vesicles by inducing a chronic cell infiltrate and the formation of organized periparasitic granuloma, fibrosis, and necrosis. T H 2 cytokines could be responsible for the ineffective immune response.
Humans are infected by ingesting eggs shed in the feces of definitive canine hosts. The eggs hatch into slow-growing larval cysts and penetrate through the mucosa, thereby leading to blood-borne distribution of the organism. The liver is the most commonly affected organ (60%), followed by the lungs (30%), kidneys, brain, spleen, bone, mesocolon, and potentially any other viscera. The right lobe (80%) of the liver is affected more than the left lobe, and in a third of cases the cysts are multiple. Pathologically, a hydatid cyst is a fluid-filled structure delimited by three layers in E. multilocularis infection; the cysts are less well limited because no sharp separation between the parasitic tissue and the liver parenchyma is present. The poor vascularization of the parasitic mass and the superimposed bacterial infection often lead to necrosis in the central part of the cyst.
Clinical Manifestations
Clinical signs associated with echinococcosis usually develop as a result of mass effect, allergic reactions, or tissue necrosis/fibrosis. Symptoms can take 5 to 10 years to occur after the initial infestation. The initial phase of primary infection is always asymptomatic and may be maintained for many years even if the infection was acquired in childhood. The clinical manifestations are variable and determined by the site, size, and condition of the cysts. Hepatic echinococcosis is usually manifested as hepatomegaly (with or without a palpable mass in the right upper quadrant), right epigastric pain, nausea, and vomiting. In the event of a ruptured cyst, allergic reactions ranging from mild to fatal anaphylaxis may occur. Common complications include rupture into the biliary tree with secondary cholangitis, biliary obstruction or extrinsic compression, subphrenic abscess formation, and intraperitoneal rupture with anaphylaxis. Up to 40% of infected patients can develop hydatid cyst suppuration. Segmental or lobar hepatic atrophy can occur in cases of portal vein or bile duct obstruction due to large expanding cysts.
Diagnosis
The diagnosis is usually made at a stage when a fully developed and still proliferating cyst has already induced an immune response in the host. In addition to the history and clinical examination; the diagnosis is based on a combination of imaging techniques. Thus clinical findings such as a space-occupying lesion and residence in an endemic region are suggestive of cystic hydatid disease. Serologic tests (hemagglutination, immunoelectrophoresis, and enzyme immunoassay) are positive and confirm the presumptive radiologic diagnosis. However, a detectable immune response does not develop in some patients with cystic echinococcosis. Hepatic cysts are more likely than pulmonary cysts to elicit an immune response; it appears, however, that regardless of location, the sensitivity of serologic tests is inversely related to the degree of sequestration of the echinococcal antigens inside cysts. In seronegative individuals, a presumptive diagnosis can be confirmed by the demonstration of protoscolices or hydatid membranes in the liquid obtained by percutaneous aspiration of the cyst. More recent advances focused on the search for more potent diagnostic tools. A study published in 2012 developed a recombinant antigen and tested a 2B2t-ELISA that proved to be a promising candidate test for serodiagnosis. It showed high sensitivity and specificity, and was useful in monitoring the clinical evolution of surgically treated patients. Another more recent study prepared antigen B from E. granulosus hydatid fluid and developed IgG4 and IgG dipsticks. IgG4 dipstick had a diagnostic sensitivity of 95% and a specificity of 100%. The IgG dipstick had a sensitivity and specificity of 100% and 87.5% respectively.
Imaging techniques such as abdominal US, computed tomography (CT), and MRI are used to determine the location, number and size, morphology, and vitality of the cysts; the status of the biliary tree and involvement of adjacent or distal organs; and the diagnosis of deep-seated lesions in all organs. Chest roentgenography permits the detection of echinococcal cysts in the lungs, and CT is very helpful, especially for the diagnosis of nontypical lesions. A standardized classification system for hepatic cysts detected by US has been developed by the WHO. The most common sonographic appearance of hepatic hydatid cysts reported in 362 Egyptians patients with 558 cysts was a noncomposite anechoic pattern in 91% of the cysts, with the remaining cysts having either a rosette or honeycomb appearance.
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