Rare Case of Disseminated Cysticercosis and Taeniasis in a Japanese Traveler after Returning from India

Abstract

We report disseminated cysticercosis concurrent with taeniasis in a 31-year-old male Japanese, who had visited India three times and stayed for 1 month each time during the previous 1 year. The patient presented increasing numbers of subcutaneous nodules and expelled proglottids, although numerous cysts were also found in the brain in imaging findings, though no neurological symptoms were observed. Histopathological and serological findings strongly indicated cysticercosis. We found taeniid eggs in his stool by microscopic examination and revealed them as the Indian haplotype of Taenia solium by mitochondrial DNA analysis. We concluded that disseminated cysticercosis was caused by the secondary autoinfection with eggs released from the tapeworm carrier himself. After confirming the absence of adult worms in the intestine by copro-polymerase chain reaction, the patient was successfully treated with albendazole at a dose of 15 mg/kg/day for 28 days. Subcutaneous and intracranial lesions had completely disappeared by the end of the treatment period.

Introduction

In contrast to the worldwide distribution of Taenia solium, cysticercosis occurs only as an imported disease in well-developed countries, whereas it remains endemic in developing areas such as Southeast Asia, Africa, and Central and Latin America. It is noteworthy that the number of patients with cysticercosis is increasing in some non-endemic countries, as a result of increases in immigrants from endemic areas.^1–4

As for infection in international travelers to endemic areas, cysticercosis tends to occur in those staying for a long-term period, with a single or few cysticerci lesions developing after ingesting the eggs of T. solium.⁵ Cysticerci, the larval stage of T. solium, are spread throughout the human body including the central nervous system. However, disseminated cysticercosis is rare, with ∼50 cases reported worldwide, most occurring in native residents of India^6,7; here, we report a disseminated cysticercosis case in a Japanese man who traveled to India. He harbored adult T. solium at first and cysticercosis was caused as a secondary autoinfection by eggs produced by the adult worm.

Case presentation

A 31-year-old Japanese man initially noticed a single subcutaneous painless nodule in the left neck in December 2009. He subsequently noted the gradual appearance of additional lesions. Worm fragments were passed in stool in April 2010, but were not brought to medical attention. The patient visited the Mie University Hospital on June 18, 2010. A medical history obtained at that time revealed that he had visited India three times in the period between August 2008 and April 2009, and spent 1 month there during each visit. While in India, the patient stayed with a local host family and was treated with hospitality including daily meals, which often included grilled pork and fresh vegetables, though never raw meat or fish. A physical examination showed that more than 10 subcutaneous lesions in total were palpable in the left inferior eyelid, left wing of the nose, lower jaw, neck, and left lateral abdomen areas. Skin biopsy specimens obtained from his body trunk appeared as a white cyst (Figure 1A ), and showed characteristics of scolex and an invaginated neck (Figure 1B). On June 23, 2010, a computed tomography scan from the neck to the pelvis revealed more than 20 subcutaneous lesions (Figure 2 ). In addition, magnetic resonance images of the brain on the same day showed 30 small cysts within the parenchyma, 4–8 mm in diameter, most of which were associated with ring enhancement and some with peri-lesion focal edema (Figure 3A ), though no neurological symptoms were observed. In addition to histopathological and imaging findings, a serological test using T. solium cysticercus-specific antigens by immunoblots⁸ indicated cysticercosis at the Asahikawa Medical University (Figure 4A ). The patient remembered passing noodle-like material in his stool several times until July 2010. Based on his report, taeniasis was treated using Gastrographin on July 14, 2010 at Mie University Hospital, but no worms were expelled. Although we could not detect adult worm(s), we found taeniid eggs in his stool corrected on 13 July 2010 (figure not shown) and copro-polymerase chain reaction (PCR)⁹ and copro-loop-mediated isothermal amplification (LAMP)¹⁰ carried out at Asahikawa Medical University, which revealed them as the Indian haplotype of T. solium by mitochondrial DNA analysis (GenBank accession no.: AB066489).¹¹ Thus, the patient was diagnosed with disseminated cysticercosis in contiguity with taeniasis.

Figure 1.

Macroscopic and microscopic findings of biopsied specimen from trunk area. (A) The subcutaneous white round-shaped cyst is a viable cysticercus. (B) Cysticercus section showing an invaginated neck, and scolex with two suckers and hooklet (H-E stain, ×40).

Figure 2.

Computed tomography was performed from the neck to pelvis. Cysticerci were found in (A) each cheek, (B) the lower jaw, (C and E) chest and abdominal walls, and (D and F) the lower back. There were more than 20 cysticerci spread throughout the body of our patient.

Figure 3.

T2WI brain magnetic resonance images obtained before and after treatment. (A) Multiple cysts with well-defined thin cyst walls and scant perilesional focal edema were seen within the parenchyma before treatment. (B) Following a 28-day course of albendazole, nearly all of the lesions had disappeared.

Figure 4.

Results of serological analyses using Taenia solium-specific antigens. (A) Immunoblot analysis with serum samples obtained before and after treatment. Albendazole was administered at a dose of 400 mg b.i.d. for 28 days. Each strip was probed with an individual serum sample at 1:20 dilution. Lane N, negative control; lane P, positive control; lane 1, before treatment, lane 2, Day 0 before start of chemotherapy; lane 3, Day 28 after start of chemotherapy; lane 4, Day 30 after stopping chemotherapy; lane 5, Day 90 after stopping chemotherapy. Serum sample reacting antigens between 10 to 30 kDa is serologically diagnosed as cysticercosis. (B) Kinetics of anti-T. solium-specific antigens antibody levels obtained by using enzyme-linked immunosorbent assay (ELISA). Start of chemotherapy is at Day 0.

The patient was admitted to the Department of Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, on August 2, 2010 for treatment. Hematological, biochemical, and serological data on admission were within normal ranges. Initially, we attempted to treat taeniasis, since it was likely that the patient was carrying an adult worm in the intestine, and because of a second episode of expelling segments 1 week before admission. Re-administration of Gastrographin into the duodenum resulted in no expelled worms; furthermore, repeated stool examinations including microscopic and copro-PCR⁹ and copro-LAMP¹⁰ were negative for eggs, suggesting that the patient had unknowingly expelled the worm. Next, albendazole was used at a dose of 400 mg twice a day for 28 days with a corticosteroid (prednisolone 1 mg/kg/day) for the disseminated cysticercosis, and an anti-epileptic drug, valproate sodium, was also administered for seizure prophylaxis. Although fever, headache, and tenderness of the subcutaneous nodules appeared on Day 3 after initiation of treatment, those symptoms improved within the same day. During the therapeutic course, the subcutaneous nodules gradually disappeared and magnetic resonance images of the brain revealed complete disappearance of the parenchymal lesions by the end of the treatment period (Figure 3B), at which time the anti-epileptic drug was terminated. A gradual decrease in the antibody level through the treatment was observed (Figure 4B). The patient has been asymptomatic for more than 6 months.

Discussion

A survey of literature published between 1981 and 2011 concerning neurocysticercosis in international travelers found a total of 35 reports documenting 52 patients.⁵ Considering the millions of people who have traveled from non-endemic to endemic countries during that period, the occurrence of cysticercosis is very low.⁵ One risk factor for travelers to acquire this disease seems to be long-term trips of several years duration. The most prevalent form of neurocysticercosis, occurring in ∼40% of the cases (21 of 52), was a single parenchymal cyst noted in neuroimaging findings. The remainder of the cases included calcified cysticerci, extraparenchymal, including ventricular and subarachnoid cysts, hydrocephalus, and spinal cysticercosis, but not disseminated cysticercosis. These cases are expected to be infected with eggs in foods or water or through some contact with tapeworm carriers. Our patient had three short-term trips to India and presented disseminated cysticercosis involving the brain with numerous lesions after he was infected with adult T. solium during his stay in India. To our knowledge, this is the first description of disseminated cysticercosis in a traveler caused as a secondary autoinfection with eggs released from him and who harbored adult T. solium after eating some local foods during his stays in India.

Human cysticercosis is caused by dissemination of cysticerci of T. solium. When T. solium eggs are ingested by humans, oncospheral embryos hatch and penetrate the intestinal tissue, and then spread throughout the whole body by the bloodstream. In experimentally infected pigs, establishment of larval cysts was reported to take ∼3 months.¹² The infection is commonly caused by fecal-oral contamination with eggs, which originate from the feces of a tapeworm carrier (direct human-to-human contact, for example living in the same household).¹² However, this mode of infection might not be true for the present case, because none of the other members in the host family were apparently ill.

Recently, it was reported that active taeniasis is associated with a heavy burden of cysticerci.^13,14 Tapeworm carriers are continuously exposed to internal autoinfection (regurgitation of gravid proglottids into the stomach)¹⁵ and external sources (fecal-oral route).¹² On the basis of the travel history and clinical course of our patient, we speculated that he was infected with the parasite during his travels, most likely during the last visit in March–April 2009. After returning to Japan, the patient became a taeniasis carrier. Because it is difficult to evaluate internal versus external autoinfection, we have to stress that this disseminated cysticercosis case was caused by adult worm(s) of T. solium and he got the infection in India through eating local foods. As stressed by several others, tapeworm carriers are the most at risk for secondary cysticercosis including disseminated cysticercosis.

Despite the numerous cystic lesions that spread to the brain, there were no neurological symptoms, such as seizure, focal neurologic signs, or pseudohypertrophy of muscles, which are frequently seen in disseminated cysticercosis patients. Each of the disseminated cysticerci in this case was considered viable based on magnetic resonance imaging findings, which corresponded well to images of cysticerci in the early stage of cysticercosis. It is well known that clinical symptoms of neurocysticercosis are related to the number, location, size, and stage of the cysticerci.^13,16 When the parasites reach an organ, they encyst and remain as viable cysts. This phase may last for years and is often clinically silent, because viable cysts are protected by the blood-brain barrier and successful sequestration from host immune responses. There is one report indicating that a cysticercus survived silently for more than 10 years.¹⁷ Clinical symptoms often appear from degeneration of cysts and immune responses evoked thereafter. Considering that his infection very recently occurred, it is quite understandable that the present patient showed no symptoms except for subcutaneous palpable cysts.

An important question in such cases is whether taeniasis or cysticercosis should be treated first. Because treatment of a taeniasis carrier who may contaminate the hospital is important to prevent environmental contamination and terminate autoinfection, we treated the taeniasis first in our patient. Before the second treatment with Gastrographin in the Tokyo Metropolitan Bokutoh General Hospital, the tapeworm had already been expelled from the carrier, and because copro-DNA could not be detected after it was confirmed during the first treatment in Mie University Hospital. Although praziquantel and niclosamide are used extensively for taeniasis treatments in endemic areas, the former is highly destructive to the worm, whereas the latter cases have much less destruction however is not highly effective for expelling an adult worm.^18,19 Because niclosamide cannot be commercially available in Japan, a Gastrographin injection method is the first choice for treatment of taeniasis solium and several Japanese physicians have reported successful complete ejection of Diphyllobothrium nihonkaiense, Taenia saginata, and T. solium without destruction with such a technique.^20–22

In this patient, we administered albendazole at a dose of 15 mg/kg/day for 28 days, oral prednisone (1 mg/kg/day) for 2 weeks, and valproate sodium. Transient fever, headache, and tenderness of subcutaneous nodules seen on Day 3 of treatment may have been the result of an inflammatory reaction. The subcutaneous and intracranial lesions completely disappeared after 4 weeks. There is no established treatment of disseminated cysticercosis. Although control of lesions in the central nervous system is closely related to patient prognosis, treatment of disseminated cysticercosis should be performed following management of neurocysticercosis, which may consist of anti-parasitic, anti-epileptic, or anti-inflammatory treatments and surgery. An individualized combination treatment is considered to be better for each patient based on cyst location, level of inflammation, and clinical presentation. Presently, use of anti-parasitic therapy has obtained consensus among experts in cases of parenchymal neurocysticercosis with viable cysts. Two cysticidal drugs, albendazole and praziquantel are well known. The superiority of either albendazole or praziquantel as first-line treatment of neurocysticercosis is still controversial.^23,24 Treatment with those drugs, especially praziquantel, may be associated with severe adverse reactions, which result from a massive release of antigens causing local tissue swelling and generalized reaction.^18,25 Use of a corticosteroid would likely decrease the incidence of such complications.^23,24 An albendazole dose of 15 mg/kg/day for 30 days has been used in many cases of disseminated cysticercosis,^6,26,27 though low dose and short duration (12 mg/kg/day for 8 days) regimens have also successfully treated the disease.²⁸ Additional deposits of cases and investigations are needed for the establishment of proper care of patients affected by disseminated cysticercosis.

This is a rare case of secondary disseminated cysticercosis caused by autoinfection in a taeniasis carrier. Taeniasis caused by T. solium was confirmed by copro-PCR and copro-LAMP with microscopic observation of taeniid eggs. Cysticercosis confirmed by histopathology of resected subcutaneous lesion, neuroimaging, and serology was successfully treated with albendazole.