STRONGYLOIDES STERCORALIS: PARASITOLOGY
Strongyloides stercoralis has the most complex life cycle of all the intestinal nematodes—and the greatest risk of life-threatening, overwhelming infection. The adults measure only 2 mm in length, making them the smallest of the intestinal nematodes. The male is seldom seen within the human host, suggesting that the female can conceive parthenogenetically in this environment. Strongyloides eggs are not diagnostically important because they usually hatch within the intestinal wall, releasing microscopic rhabditiform larvae. These larvae then develop into larger infectious filariform larvae. These larvae, which measure about 16 by 200 μm, can be distinguished from the similar larval stage of the hookworms by their short buccal cavity and large genital primordium (Figure 54–11).
Smallest intestinal nematode adults
Larvae differ slightly from hookworm
Strongyloides stercoralis. A–C. Structure of rhabditiform larvae, filariform larvae, and adult worm. D. Filariform larvae (arrow) in lung surrounded by fibrin and inflammatory cells. (D, Reproduced with permission from Connor DH, Chandler FW, Schwartz DQ, et al: Pathology of Infectious Diseases. Stamford, CT: Appleton & Lange, 1997.)
Three different life cycles have been described for the Strongyloides nematode (Figure 54–12). The first, or direct cycle, is similar to that observed with the hookworms. Adult females live in the small intestinal mucosa, where they lay eggs. These eggs often hatch within the intestinal tissue, releasing rhabditiform larvae that work their way out to the GI lumen. After these larvae are passed in the stool, they molt in the soil to become larger, infectious filariform larvae, which can penetrate human skin just like hookworms—or be ingested on soil-contaminated food. After transport from the skin to the lung (Figure 54–11D) via the vascular system, they are coughed up and swallowed, then mature into adults in the small bowel. In the second, or autoinfective cycle, the rhabditiform larva’s passage from the colon to the outside world is delayed by constipation or other factors, allowing it to transform into an infective filariform larva while still within the body of its host. This larva may then invade the internal mucosa (internal autoinfection) or perianal skin (external autoinfection) without an intervening soil phase. Thus, S stercoralis—unlike any of the other intestinal nematodes—has the capacity to multiply within the human body. The worm burden may increase dramatically, and the infection may persist indefinitely, without the need for reinfection from the environment—and with potentially dire consequences to the host, as described later. In the third, or free-living cycle, the rhabditiform larvae are passed in the stool and deposited on the soil, where they develop into free-living adult males and females. These adults feed on bacteria in the earth and may propagate several generations of free-living worms before infective filariform larvae are again produced. This cycle creates a soil reservoir that may persist even without continued deposition of feces.
✺ Added Complexity: Direct cycle resembles hookworm, except larvae develop in human gut
✺ Further Complexity: Development of filariform stage in gut produces human autoinfection
Adults can also develop in soil, producing sustained life cycle without humans
Strongyloides life cycle. [Redrawn from Centers for Disease Control and Prevention (CDC).]
The distribution of S stercoralis parallels that of the hookworms, although it is less prevalent in all but tropical areas. It infects 90 million individuals worldwide, including 400 000 throughout the rural areas of Puerto Rico and the southeastern sections of the continental United States. Like hookworm infection, S stercoralis is generally acquired by direct contact of skin with soil-dwelling larvae, although infection may also follow ingestion of filariform-contaminated food. Transformation of the rhabditiform larvae to the filariform stage within the gut can result in seeding of the perianal area with infectious organisms. These larvae may be passed to another person through direct physical contact or may autoinfect the original host. In debilitated and immunosuppressed patients, transformation to the filariform stage occurs within the gut itself, producing marked autoinfection or hyperinfection.
Distribution like hookworm but less common
Infection by ingestion of filariform larvae also occurs
PATHOGENESIS AND IMMUNITY
Invasion of the intestinal epithelium may accelerate epithelial cell turnover, alter intestinal motility, and induce acute and chronic inflammatory lesions, ulcerations, and abscess formation, all of which may play a role in the malabsorptive syndrome that frequently characterizes clinical disease. Steroid- or malnutrition-related immunosuppression of the GALT appears to accelerate the metamorphosis of rhabditiform to filariform larvae within the bowel lumen, enhancing the frequency and intensity of autoinfection. There is little evidence that protective immunity develops in the infected host.
Damage to intestinal mucosa may cause malabsorptive syndrome
✺ Immunosuppression enhances risk of autoinfection by accelerating larval development
STRONGYLOIDIASIS: CLINICAL ASPECTS
Patients with strongyloidiasis often have no symptoms at all. They may present with a history of “ground itch,” or with the pulmonary disease seen in both ascariasis and, less often, in hookworm infection. The intestinal infection itself is usually asymptomatic. With heavy worm loads, however, the patient may complain of epigastric pain and tenderness, often aggravated by eating. In fact, peptic ulcer-like pain associated with peripheral eosinophilia strongly suggests strongyloidiasis. In severe infections, the biliary and pancreatic ducts, the entire small bowel, and the colon may be involved. With widespread involvement of the intestinal mucosa, vomiting, diarrhea, paralytic ileus, and malabsorption may be seen.
Pulmonary and intestinal manifestations can be like hookworm and Ascaris infections
External autoinfection produces transient, raised, red, serpiginous lesions over the buttocks, abdomen, and lower back caused by larval invasion of the perianal area, called larva currens. If the patient is not treated, these lesions may recur at irregular intervals over a period of decades; they are particularly common after recovery from a febrile illness. Over 25% of British and American servicemen imprisoned in Southeast Asia during World War II continued to demonstrate such lesions before diagnosis and treatment some 40 years after exposure.
External autoinfection causes lesions over buttocks, abdomen, and back
✺ Autoinfection may persist for decades
Massive hyperinfection with strongyloidiasis may occur in immunosuppressed patients, especially in those receiving glucocorticoid therapy, which reduces the GALT’s T-lymphocyte–mediated cellular immune response that usually keeps Strongyloides under control. Because the original infection may have happened years earlier, and because autoinfection is often asymptomatic, patients and physicians often fail to appreciate the presence of these infections. This can have catastrophic consequences if immunosuppressive medications are initiated before the infection is cured. In these tragic cases of hyperinfection, larvae cause severe enterocolitis and disseminate throughout the body to organs including the heart, lungs, and central nervous system. The larvae may carry enteric bacteria with them, producing gram-negative bacteremia and occasionally gram-negative meningitis that may result in death. Inexplicably, this phenomenon has been unusual in acquired immunodeficiency syndrome (AIDS) patients, even in areas where strongyloidiasis is highly endemic. Immunodeficiency due to another retrovirus, human T-lymphotropic virus-1 (HTLV-1), has a stronger association with Strongyloides hyperinfection.
✺ Massive hyperinfection occurs in immunosuppressed, but uncommon in AIDS
✺ Consider ruling out strongyloidiasis before immunosuppression in patients with concerning symptoms or risk factors
The diagnosis of strongyloidiasis is sometimes made by finding rhabditiform larvae in the stool. Preferably, only fresh specimens should be examined to avoid the confusion induced by the hatching of hookworm eggs with the release of their look-alike larvae. The number of larvae passed in the stool varies from day to day, often requiring the examination of several specimens before the diagnosis of strongyloidiasis can be made. When absent from the stool, larvae may sometimes be found in duodenal aspirates or jejunal biopsy specimens. If the pulmonary system is involved, the sputum should be examined for the presence of larvae. Agar plate culture methods may recover organisms that go undetected by microscopic examination. Serology via enzyme-linked immunosorbent assays for antibodies to excretory–secretory or somatic antigens can also be performed; if positive, these results carry a strong positive predictive value. Unfortunately, serology’s negative predictive value is less reliable. During hyperinfection, unfortunately, the sputum may teem with filariform larvae. Whereas eosinophilia is common in autoinfection, it is usually absent in hyperinfection; indeed, it is the lack of these cells that seems to predispose patients to hyperinfection in the first place.
✺ Symptomatic or hyperinfection: filariform larvae in sputum, no eosinophilia
✺ Subclinical autoinfection: serology, eosinophilia, rhabditiform larvae in stool or duodenal aspirates
All infected patients should be treated to prevent the buildup of the worm burden by autoinfection and the serious consequences of hyperinfection. The drug of choice for uncomplicated strongyloidiasis is two doses of oral ivermectin, another contrast with the other intestinal nematodes. In hyperinfection syndromes, supportive treatment and antibacterials are essential to address sepsis; ivermectin therapy must be extended for at least 1 week, and potentially as long as 6 months, if the underlying immunosuppression cannot be removed. The cure rate is significantly less than 100%, and stools should be checked after therapy to see whether retreatment is indicated. Patients who have resided in an endemic area at some time in their lives should be assessed for S stercoralis both before and during steroid treatment or immunosuppressive therapy. Medical personnel caring for patients with hyperinfection syndromes should wear gowns and gloves because stool, saliva, vomitus, and body fluids may contain infectious filariform larvae.
✺ Treat autoinfection cycle to prevent subsequent hyperinfection
✺ Outcomes usually poor in hyperinfection
Medical personnel can become infected with filariform larvae
Which of the gastrointestinal helminth infections described earlier could be prevented with improved disposal of human waste?