Management of Echinococcus multilocularis in pregnancy: A case report

Abstract

Background

Alveolar echinococcus (AE) is a zoonosis caused by the Echinococcus multilocularis parasitic tapeworm, associated with substantial morbidity and mortality. Management of AE in pregnant people presents many challenges including the risk of disease progression due to the immunologic changes in pregnancy and potential teratogenicity of antihelminthic drugs. Currently, there is limited guidance on the perinatal management of AE. Therefore, we present a case of AE in a pregnant person highlighting some of the challenges around antepartum, intrapartum and postpartum care with this serious infection.

Case

A 20-year-old female became pregnant ten months after the initial diagnosis of AE with peritoneal dissemination. After discussion of risks and benefits of continuing with the pregnancy, the decision was made to closely monitor the patient with monthly liver ultrasound exams. Due to potential risk for teratogenicity, she was advised to hold albendazole treatment during first trimester with the understanding that she would restart if lesions formed or enlarged. The patient chose to continue abstaining from albendazole for the entire pregnancy. During the albendazole-free period, no new cystic growths or enlargement of existing cysts were observed in close follow-up. She had an uncomplicated delivery at 39.5 weeks via Cesarean section. Albendazole was restarted following delivery, and due to concerns about infant albendazole exposure, formula feeding was preferred over breastfeeding.

Conclusion

AE poses many management challenges in pregnant people. Effectively managing these challenges requires in-depth discussion about potential risks of withholding or continuing treatment, a shared decision-making approach, and close disease monitoring throughout the pregnancy.

Introduction

Echinococcosis is a parasitic infection caused by tapeworms of the Echinococcus. It includes cystic echinococcosis, caused by Echinococcus granulosus, and alveolar echinococcosis (AE), caused by Echinococcus multilocularis. AE has been reported in China, Central Asia, Russia and Central Europe [1]. In North America, previous cases have primarily been reported in Northwestern Canada, Alaska and the Central Northern United States [2], [3], [4].

E. multilocularis is primarily transmitted through a fecal-oral route, often originating from infected wild foxes and coyotes and occasionally through household cats and dogs [4]. The tapeworm larvae form slow-growing, poorly circumscribed cysts predominantly in the liver. Common presenting symptoms include abdominal pain, fatigue, and weight loss [5]. While AE is rare, it carries a mortality over 90 % in those who are untreated or inappropriately treated [6]. Treatment typically involves combination of antihelminthic drugs and surgical resection of cysts. Prolonged treatment with antihelminthic drugs, such as albendazole, is recommended for several years even after surgical resection, due to a high risk of recurrence [7], [8].

Managing AE in pregnant people presents additional challenges. The immunological changes can cause abdominal cysts to enlarge, potentially causing obstetric complications. Additionally, teratogenic effects of albendazole was previously shown in animal models, and the information during first trimester use in pregnancy is limited. Clinicians must carefully weigh the potential impact of albendazole on the developing fetus against the risks of withholding treatment. In this report, we present a case of AE in a pregnant person with peritoneal dissemination, highlighting the unique challenges that are encountered in the management of this condition.

Case

A 20-year-old female from the North Central United States presented to her local health clinic with a seven-month history of intermittent right upper quadrant abdominal pain, nausea, and early satiety. A CT scan of the abdomen and pelvis revealed a multilobulated 5 cm cystic mass measuring in segment IV of the liver (Fig. 1A). She underwent surgical exploration and resection of the liver mass. Intraoperatively, numerous adhesions were noted between the right hemidiaphragm and liver with a firm, yellow mass involving segment IV. The adhesions contained small granulomatous nodules, containing a creamy exudate. Intraoperative liver ultrasonography demonstrated nodules within the left lateral liver, therefore she underwent left hepatectomy with resection of segments II, II and IV. Pathologic exam of the resected liver mass showed multiloculated cysts lined by lamellated membranes without hooklets evident (Fig. 1B-D). Echinococcus IgG enzyme immunoassay testing was equivocal and remained so on repeat testing two weeks later. Based on her geographic residence and pathologic finding, a diagnosis of E. multilocularis was made and she was started albendazole 400 mg twice daily. She was counselled on the potential teratogenicity of albendazole and advised to use two forms of reliable contraception.

Fig. 1.

Radiology and pathology slides. A) Coronal CT scan of the abdomen showing a multilobulated cystic mass (*) measuring 5 cm in segment IV of the liver. B) Hematoxylin and eosin (H&E) stain, and C) Gomori methenamine silver (GMS) stain showing parasitic membranes lining multiloculated cysts. D) H&E stain providing a detailed view of the multilayered parasitic membranes without hooklets evident.

Two months after starting albendazole, a PET MRI of the abdomen noted a decrease in the size of the cystic lesions with mild FDG avidity along the hepatectomy resection margins. A further PET MRI obtained 6 months later noted near resolution of the cystic lesion with decreasing FDG avidity along the resection. Ten months after the initial diagnosis, she became pregnant while on oral hormonal contraceptives. After consulting with infectious diseases, obstetrics, and pediatric specialists, the recommendation was to suspend albendazole treatment during the first trimester of pregnancy. However, the patient decided to discontinue albendazole for the entire duration of her pregnancy based on a concern of potential teratogenic risk. Throughout her pregnancy, she underwent liver ultrasound monitoring every two months, which showed stability in the remaining cystic liver lesions.

The pregnancy proceeded without complications, and the baby was delivered at 39.5 weeks via Cesarean section. Following delivery, albendazole was resumed. The patient voiced her concerns about potential albendazole exposure to the infant through breast milk. Further discussions involving the patient, pediatrics, obstetrics and infectious disease specialists and pharmacists was held on risks and benefits of this approach. Ultimately, a shared decision was made to avoid breastfeeding and opt for exclusive formula feeding for the infant.

Discussion

AE primarily targets the liver, but can spread to surrounding abdominal tissues and distant organs such as the lungs or brain. Albendazole is the mainstay of treatment which is classified as category C by the Food and Drug Administration [9]. Mebendazole, another benzimidazole compound with a similar mechanism of action to albendazole, is considered a second-line treatment option. Due to the insidious nature and high recurrence rate, a prolonged and often lifelong treatment is needed. Untreated patients experience high morbidity and mortality over the long term (10–15 years post-clinical presentation), whereas data on partially treated patients or those with treatment interruptions remain limited [10.], [11], [12].

Animal studies suggest a potential teratogenicity associated with albendazole use during the first trimester. However, limited human studies, particularly disaggregated by trimester, make it challenging to accurately determine risk of teratogenicity in humans [13], [14.], [15.]. There is thought to be at least a theoretical risk to developing fetuses based on the mechanism of action of albendazole and other benzimidazoles that interfere with mitotic processes by binding tubulin and inhibiting microtubule synthesis, a fundamental component of the eukaryotic cytoskeleton [18]. Previous case reports have conflicting results with some showing no adverse birth outcomes associated with albendazole use during first trimester, while others present potential links with adverse birth outcomes including teratogenicity and infantile eczema [16], [17], [18], [19], [20]. Available literature does not cite specific congenital anomalies in humans associated with albendazole therapy, potentially because of their rarity of presentation. While these case reports and cohort studies have produced often conflicting evidence, consensus emphasizes the importance of individualized care for this unique population by combining expert opinion with patient preferences [19], [21]. It is therefore important to consider a patient's concerns about potential harm to the developing fetus. Additionally, a management plan should be in place regarding radiologic monitoring and preferred treatment modalities should new or worsening symptoms develop or cystic lesions enlarge. In this case, the patient, opted to forego albendazole treatment during pregnancy without progression of the infection. It is also important to consider and discuss albendazole’s potential side effects of gastrointestinal disruption and elevated liver enzymes if the pregnant patient is interested in pursuing albendazole treatment in the second and third trimesters.

Consideration should be given to the potential transfer of albendazole metabolites to a breastfeeding infant through breastmilk, especially in cases of long-term and high dose albendazole treatment. Current literature focusing primarily on short-term and single-dose regimens of albendazole suggest minimal metabolite levels in the breastmilk that are unlikely to cause harm to the infant [22], [23]. However, albendazole therapy in the context of AE typically lasts years, challenging the generalizability of these findings to this particular patient population. While the mother in this case did not choose to breastfeed, this represented an important conversation and management consideration during her pregnancy. Further, this case emphasizes the significant knowledge gap in the literature on long-term albendazole treatment during lactation.

Intrapartum and postpartum management also involve the discussion of delivery mode (vaginal delivery vs. Cesarean section). The primary concerns influencing this decision center around and risk of intra-abdominal cyst rupture and the theoretical possibility of parasite transmission to the fetus. Available literature on this is limited, with a mouse study reporting a minimal risk of E. multilocularis on the reproductive course [24]. Pregnancy-related immunosuppression and increased placental steroid secretion can promote cyst growth [25]. Large cysts (>10 cm in diameter) or enlarging cysts (by more than 1 cm during pregnancy) are associated with adverse fetal outcomes, including low birth weight, fetal distress, oligohydramnios, and miscarriage [17]. Additionally, active peritoneal involvement poses further risks due to cyst enlargement in the liver, abdomen, or pelvis, potentially causing indirect fetal harm. Increased intra-abdominal pressure, cyst rupture during labor, and potential interference with normal labor progression should prompt consideration of a Cesarean section. Regardless of delivery mode, prophylactic administration of antihistamines and steroids should be considered to prevent anaphylactic reactions, particularly in cases involving large or thin-walled cysts [26]. Additionally, percutaneous treatment of hydatid cysts may serve as a less invasive alternative to surgical intervention during pregnancy, especially for patients with large cysts [25]. In the present case, the patient demonstrated no active peritoneal disease or new cyst formation throughout pregnancy. Nonetheless, after thorough consideration of potential risks and management options, she elected to proceed with Cesarean delivery.

While routine postnatal evaluation is standard for the newborns, there are currently no specific recommendations for infants with potential AE exposure. Serologic testing immediately after birth is not of diagnostic use since maternal antibodies remain within the child’s immune system for roughly six months. However, serology testing for Echinococcus at six, twelve and eighteen months may aid in excluding vertical transmission. The need for further testing should be guided by pathologic evaluation of the placenta and any abnormalities noted on the child’s routine postnatal exams. Pathology should examine the placenta grossly for evidence of abnormalities, especially cystic structures. Four or more slides from each abnormal region should be examined histologically and, if necessary, placental pathology and microbiology experts should be consulted.

E. multilocularis infections that are diagnosed and treated prior to or early in pregnancy improve maternal and fetal outcomes [19], but the issue remains of limited data on E. multilocularis in the settings of pregnancy, delivery and breastfeeding. Existing management guidelines are sparse but in general emphasize weighing the benefits of albendazole therapy for the pregnant individual with the potential harms of albendazole for the developing fetus or breastfeeding infant [8], [26]. These guidelines appear in agreement that brief interruption of albendazole therapy is acceptable, especially during the first trimester of pregnancy, but that therapy should be resumed as soon as possible especially in those with multiple or large cysts. While much is known about the response of the AE cysts to available treatment options, as well as the outcomes of untreated disease, the outcomes of those who experience an interruption in treatment, such as the patient described in this case report, require further investigation. There is also currently no alternative to benzimidazole (albendazole, mebendazole) treatment and no canine host vaccine (which would interrupt the transmission chain to humans) for E. multilocularis, prompting a need for urgent discovery and development [8]. Notably an increase in AE infection in domestic dogs and wildlife has been seen recently, likely related to urbanization and its associated ecological changes. In North America, a European genotype of AE has been found in the past few decades, likely related to importation of dogs or foxes from Europe [27]. This increase in prevalence highlights the challenges that AE poses for pregnant people and the need for clarity of management. This case has helped to emphasize that effectively managing these challenges requires in-depth discussion about potential risks of withholding or continuing treatment, a shared decision-making approach, and close disease monitoring throughout the pregnancy.

Author contributions

Zoe Fanning, Maryam Mahmood and Isin Yagmur Comba contributed to manuscript conceptualization. Zoe Fanning wrote the original draft, while Zoe Fanning, Maryam Mahmood, Omar Abu Saleh and Isin Yagmur Comba each contributed to editing and revision. Omar Abu Saleh provided radiology and pathology images.

CRediT authorship contribution statement

Comba Isin Yagmur: Writing – review & editing, Conceptualization. Abu Saleh Omar: Writing – review & editing, Visualization. Mahmood Maryam: Writing – review & editing, Conceptualization. Fanning Zoe: Writing – review & editing, Writing – original draft, Conceptualization.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Consent to publish

The participant has verbally consented to the submission of the case report to the journal.

Ethics approval

This is an observational study. The Mayo Clinic Institutional Review Board has confirmed that no ethical approval is required.

Funding

No funding was received to assist with the preparation of this case report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors have no competing interests to declare that are relevant to the content of this article.