The Brief Case: the Boy Who Cried Worm

CASE

A 13-year-old, otherwise healthy, male patient living in northeast Ohio presented to the pediatric infectious diseases clinic, reporting to have seen multiple worm segments in his stool during the previous 13 months. With the first occurrence, the specimen was brought to a local urgent care center but was not sent for further identification. The patient was prescribed albendazole (400 mg), with a repeat dose in 2 weeks.

Thirty-four days after the first occurrence, the patient reported seeing another worm segment in his stool. The specimen was not collected. The patient presented to his primary care physician (PCP), who ordered a stool ova-and-parasites (O&P) examination, which returned negative results. One hundred days after the first occurrence, the patient observed another worm segment in his stool. He presented to a local urgent care center, no additional testing was performed, and the patient was again prescribed albendazole (400 mg), with a repeat dose in 2 weeks. The patient observed worm segments in his stools on four additional occasions over the following 7 months. A total of 337 days after the first occurrence, the patient presented to his PCP again, but none of the specimens was collected or photographed. The patient’s PCP ordered another stool O&P examination, which yielded negative results. One month later, a third stool O&P examination was performed and also returned negative results. The patient was then referred to pediatric infectious diseases.

Other than observing worms in his stools, the patient was asymptomatic. The patient lived on a farm, where his family raised chickens, lambs, and pigs. The family also owned dogs. All animals were reported to be healthy. The patient and his family regularly consumed fish that they caught locally or bought in grocery stores or that was prepared in restaurants. When cooking fish themselves, they used a thermometer to cook to an internal temperature of 145°F (62.8°C). The patient denied the consumption of raw fish.

The patient’s complete blood count did not have evidence of macrocytosis, anemia, or eosinophilia. Two weeks after the pediatric infectious diseases visit, a stool sample with a worm segment was submitted to the laboratory. A fourth O&P examination yielded negative results, and the suspected worm segment could not be clearly identified, possibly because the specimen had degraded. The patient passed additional worm segments in his stool 1 week later (408 days after the first occurrence). The patient’s father e-mailed photographs to pediatric infectious diseases, and he was advised to submit this specimen for identification.

The specimen received was a section of an adult tapeworm (Fig. 1). The proglottids were approximately 4 mm long and 10 mm wide, and a central uterus was visualized. No scolex was identified. Ova recovered from crushed proglottids were oval, yellow-brown, and 50 to 60 μm in length, and each had opercula and abopercular knobs (Fig. 1). Given the combined morphologic features of the adult worm specimen and the ova, the organism was identified as a diphyllobothriid tapeworm, most likely Dibothriocephalus latus (syn., Diphyllobothrium latum). The patient was treated with a single tablet of praziquantel (600 mg). Three months after treatment, the patient reported no further worm segments in his stool.

FIG 1.

(a) Strobila of the diphyllobothriid tapeworm submitted by the patient. (b) Closer view of the individual proglottids, showing that each is wider than it is long; a uterus can be seen as a dark structure in the center of the proglottid. (c and d) Ova extracted from proglottids are shown at (c) 400× and (d) 500×. Both ova are 50 to 60 μm in length and each has an operculum with a smaller abopercular knob on the opposite pole.

DISCUSSION

Diphyllobothriasis is an intestinal infection with cestodes of the family Diphyllobothriidae, also known as broad tapeworms or fish tapeworms. Diphyllobothriid tapeworms are among the largest parasites of humans. Adult worms typically grow at rate of 22 cm/day and reach a length of up to 2 to 15 m, although a maximum length of 25 m has been reported (1, 2).

Recent morphologic and molecular data have led to reorganization of the genus Diphyllobothrium into multiple genera (3, 4). Fifteen species are reported to infect humans, but four in particular are the most well described (1–4). The resurrected genus Dibothriocephalus contains three of these species, namely, D. latus, Dibothriocephalus nihonkaiense (syn., Diphyllobothrium nihonkaiense), and Dibothriocephalus dendriticus (syn., Diphyllobothrium dendriticum) (3, 4). Adenocephalus pacificus (syn., Diphyllobothrium pacificum) is the fourth pathogenic diphyllobothriid that is well known (3–6).

In general, diphyllobothriasis is endemic in the circumpolar regions of the Northern Hemisphere, but cases have been reported throughout the world. There have been recent increases in cases from sub-Alpine Europe and the Pacific coast of South America, while cases in North America and other parts of Europe have declined in recent decades (1–7). D. latus is thought to be the most common pathogenic diphyllobothriid in humans, including in the Great Lakes region of North America, where our patient resided (1–4). However, historical cases that preceded molecular identification tools might have been misattributed to D. latus (4, 5).

Humans are definitive hosts of diphyllobothriid tapeworms. Unembryonated ova are passed into the stool. Under appropriate conditions, ova mature in water and hatch, releasing coracidia. Subsequently, coracidia are ingested by small crustaceans, the first intermediate host, and develop into procercoid larvae. Infected crustaceans are consumed by small fish, the second intermediate host. Procercoid larvae migrate into the deeper tissues of the fish and develop into plerocercoid larvae. Infected fish may be consumed by larger predator fish, which are paratenic hosts. In either case, humans acquire the parasite through the consumption of raw or undercooked infected fish. The plerocercoid larvae develop into adults in the small intestine, usually attaching in the ileum or, less commonly, the jejunum. Specific fish hosts are associated with specific diphyllobothriid taxa and include freshwater, marine, and anadromous fish; walleye, yellow perch, northern pike, and trout species are known fish hosts found in northeast Ohio. Fish-eating mammals and birds can also be definitive hosts (1–4).

Diphyllobothriasis is usually asymptomatic. The passage of proglottids in the stool is likely the most common way patients become aware of an infection. Some cases have mild, nonspecific symptoms, including diarrhea and abdominal discomfort (1, 2). In rare cases, a prolonged or heavy infection can lead to vitamin B₁₂ deficiency and megaloblastic anemia through the impairment of vitamin B₁₂-intrinsic factor complex absorption in the ileum (1). D. latus is more commonly associated with vitamin B₁₂ deficiency that the other diphyllobothriid species (1, 8).

The diagnosis of diphyllobothriasis typically depends on the identification of ova or proglottids from the stool. While the adult produces millions of ova per day, their discharge is periodic, and a single stool O&P examination can yield false-negative results. The sensitivity with repeat stool O&P examinations is unknown but likely does not significantly improve (9). Diphyllobothriid ova are oval (35 to 80 μm by 25 to 65 μm) and yellow-brown. The ova also have an operculum and a smaller abopercular knob at opposite poles. Trematode ova are also operculated, but there is little to no size overlap with diphyllobothriid ova; trematode ova are also more likely to be detected in stool (1, 2, 4). Diphyllobothriid proglottids are wider than they are long (2 to 4 mm long and 10 to 12 mm wide), and a rosette-shaped uterus may be found. Each proglottid contains one set (or rarely two sets) of male and female reproductive organs. Unlike the other cestodes, diphyllobothriids have a single midventral genital pore found on their proglottids. The diphyllobothriid scolex is usually not found in stool samples but has the distinct appearance of attachment grooves (bothria) on the dorsal and ventral sides (1–4). Table 1 summarizes the morphologic features of diphyllobothriids that usually distinguish them from other cestodes. However, molecular tools are the most reliable means for identification of diphyllobothriids at the species level (1–4). These methods are typically limited to use in research, but efforts have been made to apply these technologies to clinical diagnostics (10, 11).

TABLE 1.

Differential morphology of pathogenic cestodes^a

Cestode species	Characteristics of:
	Ova	Scolex	Proglottid
Diphyllobothriid spp.	35–80 μm by 25–65 μm, yellow-brown, oval with operculum and smaller abopercular knob; unembroynated	2–3 mm long by 1 mm wide, almond-shaped, with 2 grooves (bothria) for suckers and no hooks or rostellum	2–4 mm long by 10–12 mm wide, with uterus coiled into rosette appearance and with single central genital pore
Taenia saginata	31–43 μm, brown, spherical with thick striated shell; embryonated, with six-hooked oncosphere present within shell	1–2 mm in diam, rounded or slightly pyriform, with 4 cup-like suckers and no hooks or rostellum	16–20 mm long by 5–7 mm wide, with uterus appearing as central stem with 15–20 main branches on each side and with single lateral genital pore
Taenia solium	31–43 μm, brown, spherical with thick striated shell; embryonated, with six-hooked oncosphere present within shell	1 mm in diam, globular or rounded, with 4 cup-like suckers and double rows of 25–30 large and small brown chitinous hooks arranged around rostellum	12 mm long by 5–7 mm wide, with uterus appearing as central stem with 7–13 main branches on each side and with single lateral genital pore
Hymenolepis nana	40–60 μm by 30–50 μm, colorless, oval, with polar filaments between inner and outer membranes; embryonated, with six-hooked oncosphere present within shell	0.3 mm in diam, globular, with 4 cup-like suckers and retractile rostellum with single row of 20–30 hooks	0.2–0.3 mm long by 0.8–0.9 mm wide, with uterus not visible and with single lateral genital pore
Hymenolepis diminuta	70–86 μm by 60–80 μm, yellow, round or slightly oval, with inner and outer membranes; embryonated, with six-hooked oncosphere present within shell	0.2–0.4 mm in diam, club-shaped, with 4 cup-like suckers and rudimentary apical rostellum without hooks	0.7–0.8 mm long by 3–4 mm wide, with uterus not visible and with single lateral genital pore
Dipylidium caninum	31–50 μm by 27–48 μm, colorless, spherical or oval, with multiple eggs in sac; embryonated, with six-hooked oncosphere present within shell	0.35 mm by 0.37 mm, rhomboid or rounded appearance, with 4 oval cup-like suckers and prominent conical rostellum with 30–150 small thorn-shaped hooks arranged in 1–7 rows; rostellum may be retracted into scolex	12 mm long by 3 mm wide, tapering at each end, with uterus not visible and with bilateral genital pores

^aAdapted from references 1 and 13.

The treatment of choice for diphyllobothriasis is a single dose of praziquantel. Niclosamide is also effective but is unavailable in many countries, including the United States (1, 2). Antihelminth benzimidazoles, such as albendazole, do not have a proven role in the treatment of diphyllobothriasis.

Avoiding the consumption of raw or undercooked fish is the best prophylaxis against diphyllobothriasis. Cooking fish to a temperature of at least 55°C destroys plerocercoid larvae (1, 12). Smoking fish does not adequately kill parasites (1, 12). The U.S. Food and Drug Administration also recommends specific freezing conditions to sufficiently kill parasites, i.e., freezing and storing at −20°C or below for 7 days, freezing and storing at −35°C or below until solid and storing for 15 h, or freezing at −35°C until solid and storing at −20°C for 24 h (1, 12). These conditions may not apply to larger fish thicker than 6 in (12). Pickling or brining fish may reduce parasite hazards, but they do not eliminate the risk (1, 12).

In summary, we present a case of diphyllobothriasis from northeast Ohio that took over 1 year to diagnose. The prevalence of this infection in the United States is low; therefore, clinicians may be unfamiliar with optimal diagnostic methods or the preferred treatment. A timelier diagnosis might have been reached with submission of one of the worm segments from earlier in the patient’s course. The patient’s family reported attention to cooking temperature in fish they prepared for themselves, but the level of care for fish cooked by others cannot be determined. There also exists the possibility that cooking and freezing practices significantly reduce the risk of infection but do not completely eliminate it. This case also highlights the fact that multiple stool O&P examinations may still have poor sensitivity for diphyllobothriasis. The albendazole courses given to our patient were appropriate for Enterobius vermicularis (pinworms), a helminth infection that is more familiar to clinicians in the United States, especially in pediatrics. However, praziquantel is the treatment of choice for diphyllobothriasis, and this case underscores the importance of a specific diagnosis in managing a suspected helminth infection. Future cases of diphyllobothriasis may benefit from the further development of molecular diagnostic tools. These methods not only may improve detection of parasites but also may better characterize the epidemiology of diphyllobothriid species worldwide.

SELF-ASSESSMENT QUESTIONS

1. Which of the following is the infective stage of diphyllobothriid tapeworms to humans?

   1. Ova

   2. Coracidia

   3. Procercoid larvae

   4. Plerocercoid larvae

2. The diphyllobothriid species most commonly associated with vitamin B₁₂ deficiency and megaloblastic anemia is:

   1. Adenocephalus pacificus

   2. Dibothriocephalus dendriticus

   3. Dibothriocephalus latus

   4. Dibothriocephalus nihonkaiense

3. Which of the following descriptions of cestode ova most likely belongs to a diphyllobothriid tapeworm?

   1. Embryonated, oval, colorless ova with polar filaments between the inner and outer membranes and a six-hooked oncosphere inside the shell; size range, 40 to 60 μm by 30 to 50 μm

   2. Unembryonated, oval, yellow-brown ova with an operculum and a smaller abopercular knob at the opposite pole; size range, 35 to 80 μm by 25 to 65 μm

   3. Embryonated, spherical or oval, colorless ova with six-hooked oncospheres inside the shell; size range, 31 to 50 μm by 27 to 48 μm; multiple eggs are found within a sac

   4. Embryonated, spherical, brown ova with a thick striated shell and a six-hooked oncosphere inside the shell; size range, 31 to 43 μm

ANSWERS TO SELF-ASSESSMENT QUESTIONS

1. Which of the following is the infective stage of diphyllobothriid tapeworms to humans?

   1. Ova

   2. Coracidia

   3. Procercoid larvae

   4. Plerocercoid larvae

   Answer: d. Humans are infected by consuming fish infected with the plerocercoid larval stage (1–4). The plerocercoid larva develops into an adult in the small intestine.

2. The diphyllobothriid species most commonly associated with vitamin B₁₂ deficiency and megaloblastic anemia is:

   1. Adenocephalus pacificus

   2. Dibothriocephalus dendriticus

   3. Dibothriocephalus latus

   4. Dibothriocephalus nihonkaiense

   Answer: c. Of the diphyllobothriids that infect humans, Dibothriocephalus latus is the species most commonly associated with vitamin B₁₂ deficiency and megaloblastic anemia. This is a rare effect, and it is caused by interference with vitamin B₁₂-intrinsic factor absorption in the ileum (1).

3. Which of the following descriptions of cestode ova most likely belongs to a diphyllobothriid tapeworm?

   1. Embryonated, oval, colorless ova with polar filaments between the inner and outer membranes and a six-hooked oncosphere inside the shell; size range, 40 to 60 μm by 30 to 50 μm

   2. Unembryonated, oval, yellow-brown ova with an operculum and a smaller abopercular knob at the opposite pole; size range, 35 to 80 μm by 25 to 65 μm

   3. Embryonated, spherical or oval, colorless with six-hooked oncospheres inside the shell; size range, 31 to 50 μm by 27 to 48 μm; multiple eggs are found within a sac

   4. Embryonated, spherical, brown ova with a thick striated shell and a six-hooked oncosphere inside the shell; size range, 31 to 43 μm

   Answer: b. This choice describes the distinguishing features of diphyllobothriid ova, compared to those of other cestodes. Trematode ova are also operculated, but there is little to no overlap in size between trematode and diphyllobothriid ova. Answer choices a, c, and d describe the ova of Hymenolepis nana, Dipylidium caninum, and Taenia species, respectively.

TAKE-HOME POINTS

• Diphyllobothriasis is usually asymptomatic, and patients often become aware of an infection only when they observe adult tapeworm segments in stool.

• Humans are the definitive hosts of diphyllobothriid tapeworms and acquire the parasite by consuming fish infected with plerocercoid larvae. Proper cooking or freezing of fish can prevent infection.

• Four diphyllobothriid tapeworm species are the most well described in human infection, i.e., Dibothriocephalus latus, Dibothriocephalus nihonkaiense, Dibothriocephalus dendriticus, and Adenocephalus pacificus. D. latus infection can interfere with vitamin B₁₂ absorption and on rare occasions leads to deficiency and megaloblastic anemia.

• The diagnosis of diphyllobothriasis usually relies on the identification of ova or proglottids in stool. Ova are oval, with an operculum and a smaller abopercular knob. Proglottid features that distinguish diphyllobothriids from other cestodes include greater width than length, a single central genital pore, and the uterus coiled into a rosette appearance. Multiple stool ova-and-parasites examinations or submission of a suspected worm segment may be required to make the diagnosis.

• Praziquantel is the treatment of choice for diphyllobothriasis.