Pulmonary Echinococcosis or Lung Hydatidosis: A Narrative Review

Human pulmonary echinococcosis is a zoonotic disease related to infection by the Echinococcus tapeworm species [1]. Lung involvement in this condition is epidemiologically secondary only to liver disease and has been found in approximately 20% of infected patients [2]. Most cases of echinococcosis are related to Echinococcus granulosus [3], and human infection is widespread and considered a public health issue in countries in which dogs, the main definitive hosts, live in close contact with humans and livestock [4]. Diagnosis ordinarily results from an accidental finding in a plain chest radiograph evaluation because of the delayed growth of the cysts, becoming symptomatic with the rupture of the cysts and occasionally with the development of immune-mediated reactions against Echinococcus spp. [1,2,4]. A uniform treatment regimen or approach may not be feasible because of the variability of pulmonary echinococcosis [4,5].

Notwithstanding its prevalence and boundless endemicity, the knowledge of and literature on lung hydatidosis must be expanded. Furthermore, a standard of care has not been widely endorsed or implemented outside referral centres [1,2,4,5]. We aim to summarize the main features of and evidence on lung hydatidosis from the perspective of medical and surgical treatment.

Methods

Cochrane Library and PubMed were the databases used to perform a literature review. Search terms included “pulmonary echinococcosis” and “lung hydatidosis.” The MeSH terms were “lung” [All Fields] AND {“echinococcosis” [MeSH Terms] OR (“hydatidosis” [All Fields] OR “pulmonary” [All Fields] AND “echinococcosis” [All Fields] OR “hydatidosis.” A search period from September 1, 1980 to April 1, 2020 was selected to narratively review studies from various decades, given the development in pulmonary echinococcosis management.

Epidemiology

Human echinococcosis is widespread throughout the world and has some peculiarity between cystic echinococcosis (CE) and alveolar echinococcosis (AE) [6,7]. Echinococcus vogeli and Echinococcus oligarthra, belonging to the so-called neotropical type of echinococcosis, are limited to South America, and new cases are reported rarely [8–10]. Thompson and Lymbery [11] suggested the presence of intraspecific variants of CE and introduced the concept of Echinococcus granulosus sensu lato complex. The latter includes 10 genotypes (G1-G10, with the dubious presence of genotype nine), partitioned by mitochondrial DNA sequences. Its taxonomy merges the genotypes into five species: Echinococcus granulosus sensu stricto (G1, G2, and G3), Echinococcus equinus (G4), Echinococcus ortleppi (G5), Echinococcus canadensis (G6, G7, G8, and G10) and Echinococcus felidis [2]. As indicated by a novel review of 1,661 genotyped cases published internationally, most of them are caused by Echinococcus granulosus sensu stricto [2]. Molecular identification of human cases of CE is strongly suggested for a superior comprehension of the epidemiology, pathology, and natural history of infection, especially in territories of sympatry, where different etiologic agents of CE exist [2]

Cystic echinococcosis

Attempts to map the incidence and prevalence of CE in humans have found a lack of accurate case records [3]. For example, the European Registry of Cystic Echinococcosis (ERCE) was recently launched [12], born of the Human Cystic Echinococcosis ReseArch in CentraL and Eastern Societies (HERACLES) project [13]. Most of the available data concerning cases transmitted by domestic intermediate hosts [3]. Nevertheless, with the above limits, the epidemiology of CE seems to be stable in the last 20 years, and the most recent projection of the overall burden of CE is 188,000 new cases annually [3]. Eastern and central Asia, South America, and northern and eastern Africa are endemic areas [3,14–19]. Cystic echinococcosis has been eradicated from New Zealand, and some regions of Australia, such as Tasmania, have been provisionally declared free of the disease in humans [1,20] although it is still found in Tasmanian wild and rural dogs [20]. In Western Europe [21] and North America [22], CE is not considered a cause of morbidity or mortality, and most human cases are imported, although an autochthonous cycle with low prevalence is present. Sporadic cases in the United States were reported by Moro et al. [22] in Alaska, California, and Utah. In northern Europe, the United Kingdom is endemic for Echinococcus granulosus with the highest incidence in the western isles, Shetland, and Highlands, whereas Ireland is considered to be non-endemic for CE [21]. In southern Europe, which includes Portugal, Spain, France, Greece, and Italy, CE is the most critical helminth zoonosis, with a life cycle that affects dogs and farm livestock as definitive and intermediate hosts, respectively [21].

Alveolar echinococcosis

Although AE is broadly considered an infection of the northern hemisphere, the criteria for designation of a region as endemic for Echinococcus multilocularis have not been defined routinely, widely caused by pronounced global differences in surveillance efforts and sensibility of diagnostic tools, along with variability in host assemblages and host prevalence [23]. The global annual incidence of AE is approximated to be 18,200 cases, 91% of which occur in China, notably on the Tibetan plateau [24]. Alveolar echinococcosis is also endemic in Central Asia, and both AE and CE are highly represented in Kazakhstan and Kyrgyzstan [24,25]. Human cases of Echinococcus multilocularis have been discovered recently in European countries formerly considered to be free of AE, for example, in the antecedently unrecognized areas of endemicity of France, Switzerland, Germany, and Austria [26–29]. Currently, approximately 1,600 new cases of AE have been reported in Europe up to 2019 [24]. Alveolar echinococcosis is not considered a human health issue in the United States and furthermore has not been reported in most of the southern United States [24,30].

Life Cycle

Hosts for the cestodes tapeworm may be subdivided into three categories: definitive, intermediate, and accidental [31]. The definitive hosts are carnivores, notably dogs, cats, and wild canids, in which adult tapeworms (2.0–7.0 mm in length for Echinococcus granulosus and 1.2–4.5 mm for Echinococcus multilocularis) inhabit the small intestine [31–33]. Domestic animals and other warm-blooded vertebrates, such as sheep, goats, cattle, horses, camels, and pigs, act as intermediate hosts, ingesting eggs released by carnivores; they carry Echinococcus granulosus predominantly. Rodents, deer, moose, reindeer, and bison are intermediate hosts of Echinococcus multilocularis [34–37]. Humans may accidentally act as an intermediate host, although their role in the life cycle remains unclear [34–37] (Fig. 1).

A complete life cycle takes four to seven weeks. In the small intestine of definitive hosts, cestodes scolex present a double row of hooklets, which play a pivotal role in the attachment to the intestinal mucosa. Cestodes scolex have at least two proglottids (the number of proglottids changes between causative agents, from three to six in Echinococcus granulosus and two to six in Echinococcus multilocularis), which contain numerous eggs. The eggs are passed out through the host's feces and released into the environment [31].

The intermediate hosts consume the eggs while feeding, which settle in their gut and release oncospheres that are later conveyed through blood or lymph to primary target organs. Lymph enters the portal circulation via the intestinal wall and travels to the visceral organs' capillary bed (primarily the liver, secondarily the lungs) [36,37]. In the organs, oncospheres become vesicles (metacestodes) and develop concentrically into a fluid-filled cyst. Hydatid cysts for Echinococcus granulosus are initially fluid-filled, unilocular, and rich with hundreds to thousands of protoscolices; the morphology of Echinococcus multilocularis cysts differs, with masses of numerous small cysts interconnected by dense connective tissue [32,33]. Three layers comprise the cyst: an inner germinal and nucleated syncytial layer, surrounded by an acellular laminated layer and even further externally a host-produced fibrous adventitial layer [31,38,39]. Daughter cysts could grow inside larger primary cysts. Protoscolices (or protoscolex in Echinococcus multilocularis) are the preceding step before the adult worm when reuniting with the definitive host's intestine [38,39].

Clinical Features and Diagnosis

Pulmonary echinococcosis has been described in approximately 20% of infected patients, and the lungs are the second target organ after the liver, which is distressed in nearly 70% of the cases reported [4]. Most of the infections in both lungs and liver are caused by Echinococcus granulosus sensu lato complex, unlike Echinococcus multilocularis, in which roughly the majority of primary lesions are found in the liver [37]. The majority of the subjects have single-organ involvement with solitary cysts (cysts range from 1 to >20 cm in diameter), but 10%–15% of patients have two or more involved organs [5]. Lungs are affected by multiple cysts in 20% to 30% of patients and are frequently positioned in the lower lobes, more often posteriorly than anteriorly and more often in the right lobes (approximately 50% have occurred in the right lung) [4,5,40]. Subjects with pulmonary echinococcosis are usually children or young adults (20–40 years old): in these high-risk groups, lungs may be involved in 50% of Echinococcus spp. infections [41,42].

Pulmonary disease may be classified into three main clinical scenarios: asymptomatic early phase, symptomatic stage, and complicated late phase.

Asymptomatic early phase

The initial stages of CE and AE might be asymptomatic, and CE cysts and AE lesions can persist undetected up to 15 years [4,5]. Children and young adults are often asymptomatic despite the presence of large lesions, probably because of anatomic features such as higher elasticity of the lung parenchyma and the rib cage and weaker immune response against parasites [41–43]. Subclinical or late-presenting symptoms are typical for most AE and CE patients because of the slow annual cyst growth (ranging from 1 to 5 cm per year), especially in immunocompetent patients [4,5,40]. The accelerated cyst development in patients with CE with acquired immune deficiency syndrome (AIDS) hints that immune dysregulation could take part in CE evolution [30]. Moreover, specific human leukocyte antigen (HLA) haplotypes (i.e., HLA-DR3 DQ2) have been associated with a higher susceptibility and more severe AE disease in humans due to a more pronounced T-helper cell (T_H2)-type immune response [30].

Symptomatic stage

Various symptoms are loco-regional and might be expected to cause compression or damage to bronchia, vessels, rib cage or mediastinal organs: most symptoms of pulmonary CE may be induced by mass effect exerted by the cysts on nearby tissues [44,45]. Cough, chest pain, dyspnea and hemoptysis are the most widely recognized symptomatology [4,5,46,47]. Less frequent are malaise, nausea, vomiting, and thoracic deformations [4,5,46,47]. Most lung cysts are positioned in the lower lobes, more often posteriorly than anteriorly and with involvement in half of the cases of the right lung, 40% of the left lung, and 10% bilaterally [48,49].

Late complicated stage

The presence of any complications changes the clinical presentation, morbidity, and severity of lung hydatidosis. One of the principal complications is cyst rupture that potentially could cause fever, urticaria, eosinophilia, and anaphylactic shock [50]. Lung cysts may break, causing cyst material including fragments of larval tissue and protoscolices to be spilt and eventually flow either into the bronchial tree, producing cough, chest pain, hemoptysis, or vomica [51], or into the pleural cavity, inducing simple or tension pneumothorax, pleural effusion, or empyema [52]. Mediastinal cysts may erode into adjacent structures, causing bone pain, hemorrhage, or airflow limitation [53,54]. Eosinophilia and allergic reactions are rarely seen in AE, compared with CE, because of the dense external fibrotic component that makes vesicle fluid leakage less likely [55–57]. Additional potential clinical effects of hydatid infection include immune complex-mediated disease, glomerulonephritis leading to nephrotic syndrome [58], and secondary amyloidosis [59]. Another complication is the superinfection of the cyst, manifesting as a pulmonary abscess with poorly defined margins. A ruptured cyst can get contaminated with bacteria or with saprophytic or invasive fungi, which are severe problematics [60–63]. Hydatid disease causes recurrent acute pulmonary embolism in rare cases [64]. Moreover, migration of cysts from the right hepatic lobe to the lung parenchyma, through the diaphragm has been reported [65].

Diagnosis

Radiologic diagnosis

The first step in assessing lung hydatidosis is taking a chest radiogram [66]. Uncomplicated cysts appear on chest radiographs as rounded or oval masses with smooth borders and uniform density and are surrounded by healthy lung tissue [67]. Indirect signs of lung hydatidosis on close structures (e.g., trachea, bronchi) are visible if the dimensions of cysts are relevant, such as a shift of the mediastinum, pleural reactions, or compression of the lung parenchyma causing atelectasis [67,68]. Radiograms can easily detect calcification of pulmonary cysts, but it is rare to find calcification in pulmonary echinococcosis [68,69]. A complicated cyst may appear with typical signs with variable frequencies between case series are visible in radiograms. The crescent or meniscus sign occurs as a consequence of air introduced between the pericyst and the exocyst, causing the erosion of bronchioles for cyst growth: some authors consider it as an alarming sign of impending rupture [30,67–69]. The ingress of air within the cyst may also appear as parallel arches of air with an appearance similar to an onion peel, which is called Cumbo sign [30,67,68]. The presence of an air/fluid level may be interpreted as a theoretical communication between the cyst and the tracheobronchial tree [30,67,68]. The water lily or Camelotte sign follows the collapse of the entire endocyst, in which the crumpled internal layer floats freely in the cyst fluid [30]. The fluid component might be expelled in the tracheobronchial tree, and the remaining solid component of the cyst gives rise to a mass inside a cavity, or Monod sign [67–69].

A computed tomography (CT) scan is useful to identify better specific details of the lesions and their neighboring structures, helping to exclude alternative differential diagnoses. In intact cysts, a CT scan may reveal a thin rim was defining the perimeter [48]. Small cysts, undetectable by a chest radiogram, may be detected with the better imaging definition provided by CT scanning, which is also valuable in the case of problematic cysts, for example, it can detect a cyst wall defect in a ruptured cyst [70]. Infected cysts show in CT scans as poorly defined masses with increased internal density and contrast enhancement around the cyst wall (the ring enhancement sign) after the injection of a contrast substance. Computed tomography scanning can decode the cystic nature of the lung mass and supply precise localization to plan the surgical treatment of complicated cysts [70,71].

Ultrasonography is helpful in most cases, providing excellent images only when the cysts are nearby the pleural surface [72]. Most importantly, however, ultrasound examination of the liver may reveal concomitant liver involvement in up to 15% of individuals with lung CE [73]. Contrast-enhanced ultrasonography, based on pulsating blood flow imaging, may be used to detect small AE lesions and differentiate them from abscesses and tumors [72,73].

Magnetic resonance imaging (MRI) might have a complementary role and theoretically better diagnostic value compared with CT scan. Lung cysts exhibit hypointensity in T1-weighted images and hyperintensity in T2-weighted images, with some differences depending on the state of ripeness [67,68]. Fluorodeoxyglucose-positron emission tomography (FDG-PET) has become the preferred reference tool to evaluate their metabolic activity [74].

Serologic diagnosis

Major antigens for immunodiagnosis are contained in the hydatid fluid [75]. In the past, the Casoni intradermal test has exhibited low specificity and sensitivity; furthermore, poor standardization and moral concerns about the injection of reagents of animal origin into individuals have greatly restricted the utilization of skin tests for echinococcosis diagnosis [76]. Recorded sensitivities of serologic methods for testing patients with CE, proved by surgical enucleation, vary from 60%–90% [75,77,78]. The encystment of the metacestode prevents the stimulation of antibody-producing cells, which could induce false-negative results of serology tests [75,77,78].

For both CE and AE, serology is now limited to the validation of imaging results; it could also provide some insight on infection pressure on particular individuals (e.g., children) in different geographic areas [77,78]. The Expert Consensus of the WHO-Informal Working Group on Echinococcosis (WHO-IWGE) also uses serology results to determine possible and probable cases [79].

Treatment

A uniform treatment regimen or approach may not be feasible because of the variability of pulmonary echinococcosis. No clinical trials have compared the different treatment approaches. Cyst size, characteristics, position in the lung and clinical presentation, and the availability of medical/surgical expertise and equipment are the mainstays of echinococcosis management. Many patients with lung lesions were admitted to the hospital because of complications, mainly infection.

Surgical approach

The purpose of surgical treatment of hydatid cysts is the thorough drainage of the cyst, the eradication of the endocyst to avoid intra-operative contamination, the closure of the pericystic cavity in order to avoid extended air leakage and empyema, and the preservation of healthy lung parenchyma [80–82]. All abovementioned safety measures should be used pre-operatively to avoid the unplanned rupture of the cyst. If anaphylactic shock occurs because of cyst rupture, steroids and octreotide infusion must be administered [80,81].

For the removal of the cyst, different surgical techniques may be considered. The Ugon enucleation technique was proposed in 1952 and is suitable for a relatively small cyst. The neighboring space is fixed with packs saturated with scolicidal agent (povidone-iodine or hypertonic saline). An opening is created over the adventitia layer of the cyst to observe the underlying white-colored laminated membrane [81–83]. The anesthesiologist is then requested to apply positive pressure ventilation to the ipsilateral lung. This maneuver should induce the expulsion of the intact cyst from the cavity. The remaining cyst cavity is irrigated with an isotonic saline solution, and air leakage is obliterated using non-absorbable stitches [81].

Cystotomy with capitonnage (Barrett method) was proposed in 1952. The resection step implies an accurate incision of the lung parenchyma, preventing rupture of the cyst. The cyst is then dissected meticulously with blunt dissection and positive pressure ventilation, which assists the resection process. The cavity walls are brought close together with either interrupted non-absorbable purse-string sutures or the walls of the cyst. Last, the healthy parenchymal ends are approximated with non-absorbable sutures [80–82].

The Posadas method is an alteration of Barrett procedure and consists of closing the airway openings before capitonnage. The Perez-Fontana method of pericystectomy was recommended in 1953 and implicates the removal of the hydatid cyst along with the pericyst, which is adhered to the normal lung parenchyma [82]. There is now a consensus that the host tissue generates the pericyst in response to the cyst, and there is no need to remove it, mainly because its excision leads to a more prolonged air leak.

The needle aspiration method (Figuera technique) leads to no danger of rupture of the cyst or contamination of the pleura [80,81]. To prevent contamination, a few towels soaked in povidone-iodine solution are placed around the cyst. The syringe and catheters are outside the chest cavity. Then the pericyst is cut with scissors and its fluid is aspirated. When the cyst is decompressed, the surrounding parenchyma is incised, and the endocyst is removed [81–83]. The air leaks are obliterated with absorbable sutures. Although parenchyma-sparing procedures are preferred, sometimes segmentectomy, lobectomy, and even pneumonectomy are required. Lung resections for the treatment of hydatid cyst disease of the lung are rarely needed. In the literature, the rate of lobectomy ranges from 0.5%–45% [80]. Indications for lobectomy are a large cyst involving more than 50% of the lung, a cyst complicated by suppurative pulmonary infection not responsive to medical treatment, multiple unilobar cysts and parenchymal impairment, and fibrosis of lung tissue in chronic cases [80–83].

The best surgical approach is decided according to the diameter of the cyst, its type (single, multiple, unilateral, bilateral), and if the cyst is intact or ruptured and associated with a liver dome cyst or with destroyed lung parenchyma [81–83]. Commonly, thoracotomy is the preferred technique for the resection of hydatid cysts of the lung. In addition, median sternotomy is useful for the treatment of bilateral anterior hydatid cysts [80–82]. Moreover, the preferred surgical approach to liver cysts penetrating the diaphragm into the right lower or middle lobe is a standard thoracic laparotomy.

Nevertheless, in recent years, minimally invasive thoracoscopic approaches, named video-assisted thoracic surgery (VATS) (either, uniportal. or multiportal), have been demonstrated to be a feasible and safe treatment strategy, especially for the treatment of small and peripheral cysts [80–84]. Reported advantages of VATS were shorter surgical time, decreased length of hospital stay, lower experienced pain, and reduced surgical morbidity [85–87] Almost certainly, in the near future, these minimal invasive approaches and probably also robotic-assisted surgery, will be adopted more widely for surgical treatment of lung hydatidosis, similarly as it occurs in lung cancer disease [88].

Outcomes after Surgical Approach

Operative efficacy, mortality, and recurrence rates vary among the different surgical procedures. In different series [89–92] enucleation (Ugon method) reaches efficacy near 95%, with mortality below 1% and a recurrence rate between 2% and 4%. Furthermore, cystotomy with the closure of bronchial openings [93–95] and cystotomy with capitonnage (Barrett technique) [96–99] share an efficacy rate of 98%–99%, with low mortality (<1%) and an acceptable recurrence rate (1%–2%). Moreover, segmental resection [90,100] or lobectomy [90,101,102] present in the literature with an efficacy near 100% coupled with low mortality (below 2%) and recurrences (<1%). Open aspiration (Figuera techniques) showed less data regarding efficacy, mortality, and recurrences. Burgos et al. [103] reported efficacy, mortality, and recurrence rates of 96%–98%, 1%–2%, and 2%–3%, respectively.

Medical treatment

Anti-parasitic drug treatment may be a first definitive option or an adjunctive therapy after surgery [79]. Albendazole has proven to be the first choice for Echinococcus spp. infections, but an alternative option is mebendazole. Praziquantel is less effective but has been studied in combination with benzimidazoles. Historically, variable periods (from two to four weeks) of anti-helminth chemotherapeutic agents are recommended pre-operatively to avoid disease recurrence caused by spillage at the time after surgical treatment of liver hydatidosis, and albendazole plus praziquantel has been found to be better in its scolicidal effectiveness compared with albendazole alone [104,105]. Nevertheless, at this time, the efficiency of pre-operative or post-operative treatment has not been studied clearly in pulmonary hydatidosis. As a convention, by translating evidence from liver hydatidosis studies, pre-operative albendazole for two to four weeks is prescribed to prevent regrowth ensuing on intra-operative spillage after surgery [104–106]. Despite this, the ideal duration of pre-operative anti-helminths treatment in pulmonary echinococcosis remains unclear.

Benzimidazoles

Benzimidazoles may be the first option in small, uncomplicated lung cysts. The cutoff size for the diameter of lung lesions is not standardized, unlike for liver cysts, for which albendazole (or mebendazole) is suggested for diameters <5 cm (CE1, WHO classification). Brunetti et al. [79], in an expert consensus, suggested that benzimidazoles should not be considered pre-operatively in more giant lung cysts. A study [84] on the clinical experience of surgical therapy for thoracic hydatidosis reported an anti-parasitic role of albendazole for multiple intra-thoracic cysts (with or without liver lesions). Medical treatment is the preferred choice when surgery is unavailable or when a thorough removal is not practicable.

Albendazole

Albendazole (Table 1) is an anthelmintic benzimidazole carbamate given orally but poorly absorbed via this route of administration (<5%) and, because of its insolubility, has not been administered parenterally [107]. In contrast with intestinal helminth species, for which drug assimilation is unnecessary, systemic parasites require an extended treatment to produce a sufficiently therapeutic drug [107,108]. Albendazole sulfoxide, the primary metabolite of albendazole, is the leading agent in systemic infections, with an elimination half-life of eight to 12 hours, and it is reasonably bound to plasma proteins (70%) [107,108]. Albendazole acts first via the inhibition of parasite β-tubulin polymerization and, second, through downstream effects, such as fumarate reductase inhibition and the interruption of energy pathways that result in parasite death [107].

Culture and in vitro tests of the susceptibility of helminths to albendazole are often impossible, and anti-parasitic effectiveness has been extrapolated by empirical testing in vivo in humans or by extrapolation from the doses used for domestic animal species [108]. In humans, definitive evidence of clinical resistance is lacking, but for Echinococcus spp., prolonged infections and intermittent treatment with anti-helminthic drugs might provide the optimal situations for the development of resistance. On the other hand, transmission to other subjects does not occur as human infection represents a dead-end for the parasite life cycle [108].

Albendazole presents a hepatic metabolism, but there is a lack of information about dose adjustment in liver impairment [108,109]. Cotting et al. [110] presented five individuals with echinococcosis and severe extrahepatic biliary obstruction, for whom the assimilation and clearance of albendazole were significantly delayed and Cmax was doubled. Albendazole diffuses well in various tissues and has been observed in urine, bile, liver, cyst walls, cyst fluid, and cerebrospinal fluid and is highly correlated with drug concentrations in plasma [108,109].

Mebendazole

Mebendazole (Table 1) belongs to the same anthelmintic class as albendazole, which has now largely replaced albendazole for Echinococcus infections. Its oral bioavailability is near 5%–10%, but with tracer doses of [3H]-mebendazole administered orally and intravenously, the absolute bioavailability was estimated to be 22%, with substantial interindividual variability [111].

Clinical data are unavailable on dose regulation in the impairment of the kidneys. Even with renal deterioration, mebendazole is mostly metabolized in the liver, so regulation is unlikely to be needed in most cases [112]. Nevertheless, some experts have suggested carefulness during long-term therapy in individuals with hepatic echinococcosis because metabolism may be impaired in such patients, leading to higher levels of the parent drug and possible toxicity [111]. Moreover, plasma concentrations were reported to be higher in a patient with cholelithiasis than in normal individuals [112,113]. The metabolites are mainly discharged in urine, and in subjects receiving long-term, high-dose mebendazole, metabolites might accumulate [113,114].

Mebendazole can be measured in many tissues, especially the liver, and in echinococcal cysts, in which the concentrations correlated well with the free mebendazole plasma concentrations four hours after administration [115,116].

Praziquantel

Praziquantel (Table 1) is a pyrazinoisoquinoline derivative effective against a broad assortment of trematode and cestode helminths [117]. Currently, praziquantel is considered to be the backbone cure for schistosomiasis and opisthorchiasis. Its absorption after the oral route of administration is left up to 80%, and it has entirely renal excretion. Its short plasma half-life necessitates administration every eight hours [117,118].

Monotherapy with praziquantel is ineffective against cystic echinococcosis. A limited trial combining praziquantel and albendazole in the span of six months resulted in a superior rate of cyst disappearance (47.4% vs. 36.4%) up to the third year, compared with 22 historical controls, which received albendazole alone [119]. This consideration remains to be proven. In vitro and in vivo, praziquantel theoretically has a role as a protoscolices in preventing the dissemination of cyst content [120,121].

Outcomes after Medical Treatments

The results obtained with medical therapy for lung hydatidosis are not always easy to interpret according to heterogeneous treatment schemes and many studies concerning liver disease [122]. The leading indicators considered to evaluate the efficacy of medical treatments were a success (cured or improved hydatidosis) and relapse rates [122]. Taking into account a lung hydatidosis series, Fattahi Masoom et al. [123], have described a large cohort of subjects (n = 119) that have been treated with three cycles of six weeks of albendazole (15 mg/kg/d) alternated with two weeks of no medication. The cure or improvement rates of individuals who finished phase 1, 2, and 3 were 42.5%, 78.3%, and 92.9%, respectively, whereas relapse rates were 0%, 4.3%, and 5%, respectively [123]. Furthermore, in a placebo-controlled study of albendazole in lung hydatidosis, Keshmiri et al. [124] reported findings for 11 subjects with a success rate of 91% in the treatment group. The same group subsequently described 29 subjects and a total of 172 hydatid cysts treated with 400 mg of albendazole twice daily (three cycles of six weeks alternating with two weeks of no medication) against 31 cysts in the placebo group. The success rate was 77.9% within the albendazole group versus 12.9% in the placebo group [125]. Regarding other medical therapies, unfortunately, we still lack data on the real-life success rate of lung hydatidosis treated with the protocol that includes mebendazole or praziquantel [122], thus future studies are warranted.

Conclusions

There is a growing tendency to manage uncomplicated cysts according to one of the main treatment options (e.g., watch and wait, surgical treatment, medical treatment, or both medical and surgical treatment) notably on the basis of host factors, comorbidities and cyst stage, size and location. Medical treatment (alone or combined) is the preferred choice when the surgical approach is not applicable or when complete removal is not achievable [126]. We believe that anti-parasitic drugs may be valuable in three specific instances: (1) in single, small, uncomplicated cysts, (2) in disseminated diseases, or (3) patients with poor surgical risk. The cyst may be ruptured with the aid of medical therapy, but the membranes associated with cysts may carry a significant risk of infection [127,128].

A standard of care has not been widely endorsed or implemented outside referral centers because of a lack of well-designed clinical trials to respond to this need and to consolidate the best practices for treating hydatidosis (Fig. 2). Any complex cyst requires an individual choice for the correct management [129,130]. In support of surgical management, alongside the removal of the parasite, surgery may also act on associated parenchymal, bronchial, or pleural damage. Nevertheless, surgery must be as not destructive as possible; enucleation is taken into consideration only in case of acute and irremediable lung damage, and lobectomy is required in just less than 10% of cases [131,132]. Proper management of hydatidosis may also be considered from an infection control perspective. Monitoring the transmission of Echinococcus spp. has a pivotal role in public health, and efforts should be focused on strengthening and improving control programs in endemic areas to reduce the incidence and burden of echinococcosis [132,133].

In conclusion, hydatidosis management must become less heterogeneous. We support treatment tailored on the individual based on the clinical scenario, host factors, and surgical risk. Strict cooperation in this process between infectious disease specialists and surgeons may optimize best practices to help create shared practical guidelines to simplify clinician decision-making.

Furthermore, we definitely need a consensus for lung hydatidosis treatment and inserting this disease to global surgery agenda will have a positive impact on acquiring high-quality data that enable us to create an evidence-based guideline for this disease.

Funding Information

No funding was received.

Author Disclosure Statement

No competing financial interests exist.