A 57-year-old woman is hospitalized for her fourth episode of unexplained Gram-negative bacteremia. The only other pertinent medical history was that the patient had recently begun treatment with corticosteroids for asthmatic bronchitis. Paradoxically, her cough got worse with this therapy and she started to experience abdominal pain and diarrhea. Likewise, the other episodes of bacteremia also followed the initiation of steroid therapy.

The patient was a resident of Michigan who had lived in rural Eastern Kentucky as a child and teenager. She was treated with antibiotics for the microorganism causing her bacteremia. Because a CT scan of the patient's abdomen showed a thickened intestinal wall, the patient underwent a small intestinal biopsy that revealed the presence of helminthic parasites attached to the mucosa. Subsequent examination of a stool specimen revealed numerous immature larvae. More developed larvae were also identified in the patient's sputum.

Question 11.1: What is the most likely causative agent?

The patient clearly has some type of helminthic infection, as indicated by the presence of larvae in the stool and sputum, as well as parasites attached to the intestinal mucosa. The larva shown in the figure indicates that the infecting parasite is a roundworm (nematode), rather than a fluke (trematode) or tapeworm (cestode). The patient has a persistent infection that is not improving, and that is unusual under the circumstances. Most intestinal nematode diseases are asymptomatic or quite mild unless the victim develops a heavy burden of adult worms. To do so generally requires repeated exposure and re-infection because most helminth parasites do not self-replicate within their hosts. Yet, given this patient's history, there is no obvious reason to suspect that she is continually being re-infected. Strongyloides stercoralis is the only intestinal nematode that is likely to produce a long-lasting infection in which the symptoms may worsen instead of tapering off if the victim is not repeatedly infected. In fact, the lab did identify the causative agent in this case as Strongyloides stercoralis.

Question 11.2: What is the life cycle of this causative agent?

The infective form of S. stercoralis is the filariform larva, which can penetrate human skin, enter the circulatory system, and migrate to the lungs. The larvae are then coughed up and swallowed, after which adults develop in the small intestine. Adult females burrow into the mucosa of the duodenum and reproduce parthenogenetically. Each female produces about a dozen eggs every day, which hatch within the mucosa and release rhabditiform larvae into the lumen of the bowel. The rhabditiform larvae are passed in the stool, after which they can either continue the direct infection cycle by developing into infective filiariform larvae (that then directly invade through the skin of a new victim or the same victim) or develop into free-living adult worms and initiate the indirect infection cycle (unusual for nematode parasites).

In the indirect infection cycle, the larvae in soil develop into free-living adults that produce eggs and larvae. Several generations of this non-parasitic existence may occur before new larvae become skin-penetrating parasites.

The most unusual feature of the S. stercoralis life cycle is autoinfection, in which rhabditiform larvae in the intestine do not pass with feces but, instead, become filariform larvae. These larvae penetrate the intestinal or perianal skin and follow their usual course through the circulatory and pulmonary systems, after which they are coughed up and swallowed. In the small intestine, they develop into new adults, and burrow into the mucosa of the duodenum, where they produce still more eggs and larvae. This cycle can persist for years, continually increasing the worm burden in the GI tract as it does so, without re-infection from outside sources. The cycle can lead to hyperinfection and massive or disseminated, often fatal infections.

Question 11.3: What was the role of the corticosteroid in this case?

As yet unknown factors of the host's immune system normally contain the ongoing autoinfection cycle of strongyloidiasis. Reduction of the host's immune response, especially by the use of glucocorticoid therapy (and much less commonly with other immunosuppressive drugs) leads to hyperinfection and the generation of large numbers of filariform larvae. In the case discussed here, it would appear that each corticosteroid treatment reduce the woman's immune response enough to promote increased larvae production in the intestine, thus leading to increased numbers of the larvae migrating to the lungs and, eventually, a worsening of the cough that is usually associated with that process. In the intestine, the increased worm load promoted by the drugs led to the development of acute intestinal symptoms such as diarrhea.

Hyperinfection with S. stercoralis can lead to dissemination of the larvae via the bloodstream to virtually any organ. Extraintestinal infections most commonly involve the lung, but can also affect the lymph nodes, liver, spleen, kidneys, pancreas, thyroid, heart, brain, and/or meninges. Intestinal symptoms of hyperinfection include diarrhea, malabsorption, and electrolyte abnormalities. Hyperinfection syndrome is associated with a mortality rate of about 85%. Bacterial sepsis, meningitis, peritonitis, and endocarditis secondary to larval spread from the GI tract are common and often fatal complications of hyperinfection syndrome.

Question 11.4: What is the geographic distribution of this pathogen?

S. stercoralis is spottily distributed in tropical areas and other hot, humid regions, and is particularly common in Southeast Asia, sub-Saharan Africa, and Brazil. The parasite is endemic to the South in the U.S., but can also be found (albeit with a lower prevalence) throughout a somewhat broader geographic area, including parts of the northern U.S. and Canada. S. stercoralis is also found in residents of mental institutions who practice poor hygiene and in immigrants and military veterans who have lived in endemic areas abroad.

Question 11.5: How is this disease treated?

All infected patients should be treated to stop the autoinfection cycle and potential dissemination of the parasite (hyperinfection). The drug of choice is thiabendazole, with mebendazole as an alternative.

Question 11.6: What precautions should be taken when caring for a victim of this disease?

Strict infection-control measures should be enforced when clinicians care for patients with a hyperinfection because stool, saliva, vomitus, and body fluids may contain the infectious filariform larvae.