Cardiac pentastomiasis and tuberculosis: The worm-eaten heart

ELSEVIER

Cardiac Pentastomiasis and Tuberculosis: The Worm-Eaten Heart Maria A. Abadi, MD, Gloria

Stephney, MS, and Stephen M. Factor, MD

Department of Pathology, Albert Einstein College
We report an autopsycaseof disseminated tuberculosisanda coexisting,extremelyrare parasitic zoonosis:pentastomiasis. Theparasitewasincidentallyfoundin the pericardialsacandepicardium, associated with tuberculouspericarditis,in a43-year-oldwomanfrom Georgiawith presumptive AcquiredImmunodeficiency Syndrome(AIDS). The cuticlewastheonly remainingintact structureof the parasite.The internalorganshadundergone autolysis,but recognizablefeatureswereapparent. Grossandmicroscopicfindingswerehighly suggestive of pentastomidspecies.The ultrastructure of the cuticlewasconsistentwith a pentastomidarthropod.This is oneof the few casesof visceral pentastomiasis reportedin North America, andthe first knownexampleof heartinvolvement.The association of the parasiticinfectionandtuberculouspericarditismakesthecaseevenmoreunusual. Cardiovasc Path01 19%:5:169-l

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Pentastomiasisis an unusual parasitic zoonosis causedby

members of the phylum Pentastomida. Two orders of pentastomids are described: Porocephalida and Cephalobaenida. Only two species of the Fbrocephalida, Annillijh armillutus and Linguatula sermta, can infect humans as secondary or temporary hosts. The definitive hosts of these endoparasites include reptiles, birds, and mammals. Fish, insects,amphibians, and rodents may be affected as secondary hosts (1,2). Pentastomiasis is an endemic zoonotic disease of humans in Africa, Malaysia, and Southern Arabia. The infection has also been reported in America and Europe (3-5). In North America, casesof ocular pentastomiasis havebeenreportedin the Southern states (6). In North Carolina a calcified nodule containing a degenerated nymph of a pentastomid parasite was incidentally discovered during laparotomy (7). In virtually all of these cases, the location as well as the morphological features were consistentwith the nymphal stageof L. set-mm.

Manuscript received June1,1995;revised July4, 1995;accepted August 8, 1995. All decisions concerning review and acceptability of this manuscript were handled by an Associate Editor of this Journal. Address for reprints: Stephen M. Factor, MD, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room F 538, Bronx, New York 10461; tel: (718) 918-4811, fax: (718) 918-4809.

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Case Report A 43-year-old black female from Georgia who allegedly had never traveled out of the United States, was a former intravenous drug user with unknown human immunodeficiency virus (HIV) status (her spouse was HIV positive). She presented to our hospital in March 1993 with a 5-month history of weight loss, fever, dry cough with occasional hemoptysis, and 2 weeks of severe pleuritic chest pain and progressive shortness of breath. The chest X ray on admission revealed diffuse interstitial nodular infiltrates with a miliary pattern. The patient wasstarted on antituberculous therapy; however, she became progressively hypoxemic and expired the day following admission.

Morphologic Findings An autopsy limited to the thoracic and abdominal cavities was performed 6 hours after the patient expired. Gross examination revealed miliary tuberculosis with involvement of multiple organs. These included the lungs, liver, spleen, kidneys, intestine, ovaries, and both thoracic and abdominal lymph nodes. Microscopically, several foci of caseating necrosis with poor granuloma formation and numerous acid-fast bacilli were noted. The heart weighed 410 g, and showed diffise tuberculous pericarditis involvement with focal exten-

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sion into the myocardium (Figure 1). In addition, multiple nonsegmentedvermiform organisms,up to 1.5 cm long and 0.2 cm in diameter, were identified in the pericardial sac, epicardium, and myocardium (Figure 2). Serial sectionsof the organismsrevealeda discontinuousthin cuticle (l-l.5 pm) with an underlying fibromyxomatous stroma containing numerousfusiform cells. A central, deeply eosinophilicmaterial resemblingdegeneratedmusclefibers wasalsopresent (Figure 3A). Sclerotizedopeningsor anterior end hookswere seenin serial anterior to posterior sectionsof one parasite (Figure 3B).

Electron Microscopy

Figure 1. Photomicrograph of the left ventricle showing extensive caseating necrosis with ill-defined granulomas (nrrav) involving epicardium and myocardium (hematoxylin-eosin x150).

On electron microscopy (EM) the only remaining intact structure of the parasitewasthe cuticle. Nonetheless,the ultrastructural appearanceof this cuticle was consistentwith a pentastomid cuticle. At low magnifications four cuticular layers were distinguished(Figure 4A): an outer epicuticle, an underlying epicuticle, a fibrillar endocuticle of variable thickness, and a densesubcuticle. An amorphouslayer was presentbeneaththe subcuticle.This layer representsthe base-

Figure 2. Anterior wall of the heartshowingseveralnonsegmented, vermiforrnlarvae(arrows)and diffusecaseouspericarditis.Note the “worm-eaten”appearance of the exudate.

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Figure 3. (a) Transverse section of the organism revealing a discontinuous, thin cuticle (arrow) and degenerated muscle (M) fibers (hematoxylin-eosin x150). (b) Cuticle containing remnants of sclerotized openings (arrows) (hematoxylin-eosin x400).

ment lamella that is usually continuous with the muscular layers. Unfortunately, the muscular layers were severely degenerated. Higher magnifications of the fibrillar endocuticle revealed increasingly unoriented fibers. Pedicellate structures known as cuticular tubercles were noted in several sections, resting on the endocuticular layer (Figure 4B). The tubercles exhibited rounded apices protruding against the epicuticle. The hooks were not identified. The ultrastructure of the cuticle of pen-

tastomids is remarkably similar to that of insects. This resemblance has been previously reported by several authors (8-12) and corresponds to the findings in this case.

Discussion The adult form and third-stage larvae of pentastomes are transparent with a cylindrical or flattened vermiform body (Figure 5). The primary larvae, however, resemble mites.

Figure 4. (a) Low-power electron micrograph of a transverse section of the parasite showing the four layers of the cuticle (0 = outer epicuticle; P = protein epicuticle; E = endocuticle; S = subcuticle) ~9,000. (b) Electron micrograph of the cuticular tubercles (TU) ~9,000.

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Figure 5. Adult pentastomides resemble helminths. They are transparent with a flattened, vermiform body. (Adult pentastomid retrieved from the lung of a snake, as provided by Dr. Tracey McNamara, Director of Pathology, NYZ Wildlife Conservation Society/Bronx Zoo.)

Figure 6. Nineteenth-century English print illustrating an itinerant Chinese doctor treating his patients with snake blood. To this date in many Asian cultures snake blood is considered a panacea and an aphrodisiac. Snakes are primary hosts for pentastomid worms, and human infection may result from ingestion of ova.

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Two distinct body regions, the cephalothorax and the abdomen, have been described (1,2). The latter exhibits braceletlike oblique rings. This pseudoannulation is due to a metamerical arrangement of the striated muscle and chitinous cuticle, which gives the pentastomid a screwlike appearance (13). in addition, the larvae possess a circular, ventral mouth and two pairs of hooks in the anterior end. The gastrointestinal tract is straight and primitive. A ventral nervous system and reproductive organs are present, but circulatory and respiratory systems are absent. The adults range from millimeters to 15 cm in length. Fully mature females are larger than males. The life cycle of penstastomes varies between species. Nonetheless, both L. serratu and A. armillafus attain maturity in the respiratory tracts of vertebrates. In the case of L. ~errara extremely rare cases of human infection by adult parasites have been reported (14). The adult form of A. armillatus is not known to affect humans. The most common infective stages of the pentastomids in man include the primary and third-stage larvae. Humans become infected by ingestion of eggs contained in respiratory secretions, blood, saliva, or fecesof the definitive hosts. The primary larvae penetrate the gastmintestinal tract of the intermediate host, migrating and encysting in various host tissues. This stage is usually asymptomatic. The third-stage larvae can also encyst and migrate. In man the third-stage larvae of L. serm2a are responsible for a self-limited nasopharyngitis known as Halzoun syndrome, or “Marrara” (15). The third stage of A. armilldus may cause diverse clinical manifestations in humans, including intestinal obstruction, pneumonitis with lobar collapse of the lung, bile duct blockage, meningitis, and even prostatitis (16). Both species can invade the subconjunctiva and reach the anterior chamber of the eye (6). Our case is unusual because exclusive involvement of the heart, with or without tuberculosis, has never been reported previously. The severity of the disease may vary; however, humans are usually highly tolerant to pentastomid infection. In other intermediate hosts such as rodents and amphibians, experimental nymphal pentastomid infection has been proven to cause mechanical tissue damage and hemorrhage secondary to migration (I?). A strong immunological reaction with prominent cellular infiltration and necrotic granulomatous response has been described (17,18). Pronounced differences have been encountered in the onset and intensity of the inflammatory response in humans and other animals. It has been proposed that the pentastomid larvae develop a protective physical barrier against inflammatory cells of the host during the infective stage (19-2 1). A layer of tegumental secretory cells termed subparietul cells are responsible for the synthesis of lamellate droplets that eventually coat the entire external cuticle. Host effector cells are trapped within this amorphous matrix. Cytotoxic activity is frequently absent, This finding partially explains the lack or limited inflammatory reaction seen in the majority of cases of human pentastomiasis. In our case the compromised immunological status of the patient may have

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played a critical role. It is also conceivable that the epicardial caseation served as a protective barrier for the organisms. Pentastomiasis is usually an incidental finding in an autopsy, a radiological examination, or during a surgical intervention. Dead nymphs are found partially disintegrated and surrounded by a fibrotic capsule with little or absent infiammation. They are often calcified with a characteristic C-shaped outline that can be appreciated radiologically (1,2,7). The pentastomes can be recognized histopathologically by the presence of sclerotized openings and apparent eosinophilic glands. More often, the parasite has disintegrated into amorphous debris. Only fragments of cuticle may remain and they are usually difficult to recognize in an old granuloma on routine hematoxylin-eosin-stained sections. Electron microscopy has been proven to be an effective and reliable tool in the identification of the cuticle. The outer epicuticle, the fibrillar, poorly oriented endocuticle, and the dense subcuticle can be easily identified by ultrastructural studies (8). Recently a specific enzyme,-linked immunoabsorbent assay (ELBA) based on a 48-kDa metallo-proteinase isolated from the frontal glands of a pentastomid termed Porocephulus crotali has been used for the detection of pentastomid infections in intermediate hosts, specifically in rats. These studies suggestthat the ELBA can be readily adapted for serodiagnosis of human pentastomiasis (22). In this case we are uncertain about the origin of the pentastomid infection. Careful questioning of the patient’s relatives Exiled to reveal any relevant travel history. No contact with animals that could serve as primary host was admitted; however, we do not know what potential folk medicines or cures were employed by the patient in the weeks prior to her death. For instance, the ingestion of blood from a primary host such as a snake, a well-known practice in certain cultures, may lead to infection (Figure 6). If this patient had traveled recently in the Southern United States, she might have come in contact with a primary or secondary host. Finally, the association between this parasite and tuberculous pericarditis is unique. It would appear that the larvae were deposited on an already infected pericardial surface, as they were observed primarily between the epicardium and pericardial layers, on the epicardial surface. Whether the tuberculous infection provided an environment more conducive to growth and possibly protected them from cellular or immunological attack is. speculative. The tute, ogy their

authms wish tothank Dr. Oscar Noya from the Tropical Medicine InstiCaracas, Venezuela; and Dr. Traccy McNamara, Director of Patholat the NYZ Wildlife Conservation Society/Bronx Zoo, New York, for valuable assistance.

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