InternalMed_Harrison

InternalMed_Harrison. Immunologically competent adults and older children who have only lymphadenopathy do not require specific therapy unless they have persistent, severe symptoms. Patients with ocular toxoplasmosis are usually treated for 1 month with pyrimethamine plus either sulfadiazine or clindamycin and sometimes with prednisone. Treatment should be supervised by an ophthalmologist familiar with Toxoplasma disease. Ocular disease can be self-limited without treatment, but therapy is typically considered for lesions that are severe or close to the fovea or optic disc.


InternalMed_Harrison

InternalMed_Harrison. INFECTION IN IMMuNOCOMPROMISED PATIENTS Primary Prophylaxis Patients with AIDS should be treated for acute toxoplasmosis; in immunocompromised patients, toxoplasmosis is rapidly fatal if untreated. Before the introduction of cART, the median survival time was >1 year for patients who could tolerate treatment for TE. Despite their toxicity, the drugs used to treat TE were required for survival prior to cART. The incidence of TE has declined as the survival of patients with HIV infection has increased through the use of cART.


InternalMed_Harrison

InternalMed_Harrison. In Africa, many patients are diagnosed with HIV infection only after developing opportunistic infections. Hence, the optimal management of these opportunistic infections is important if the benefits of subsequent cART are to be realized. The incidence of TE in under-resourced settings is not clear because of a lack of facilities for serologic testing and imaging. AIDS patients who are seropositive for T. gondii and who have a CD4+ T lymphocyte count of <100/µL should receive prophylaxis against TE.


InternalMed_Harrison

InternalMed_Harrison. Of the currently available agents, trimethoprim-sulfamethoxazole (TMP-SMX) appears to be an effective alternative for treatment of TE in resource-poor settings where the preferred combination of pyrimethamine plus sulfadiazine is not available. The daily dose of TMP-SMX (one double-strength tablet) that is recommended as the preferred regimen for prophylaxis of PcP is effective against TE. If patients cannot tolerate TMP-SMX, the recommended alternative is dapsone-pyrimethamine, which likewise is effective against PcP. Atovaquone with or without pyrimethamine also can be considered. Prophylactic monotherapy with dapsone, pyrimethamine, azithromycin, clarithromycin, or aerosolized pentamidine is probably insufficient. AIDS patients who are seronegative for Toxoplasma and are not receiving prophylaxis for PcP should be retested for IgG antibody to Toxoplasma if their CD4+ T cell count drops to <100/µL. If seroconversion has taken place, then the patient should be given prophylaxis as


InternalMed_Harrison

InternalMed_Harrison. prophylaxis for PcP should be retested for IgG antibody to Toxoplasma if their CD4+ T cell count drops to <100/µL. If seroconversion has taken place, then the patient should be given prophylaxis as described above.


InternalMed_Harrison

InternalMed_Harrison. Discontinuing Primary Prophylaxis Current studies indicate that prophylaxis against TE can be discontinued in patients who have responded to cART and whose CD4+ T lymphocyte count has been >200/μL for 3 months. Although patients with CD4+ T lymphocyte counts of <100/μL are at greatest risk for developing TE, the risk that this condition will develop when the count has increased to 100–200/μL has not been established. Thus, prophylaxis should be discontinued when the count has increased to >200/μL. Discontinuation of therapy reduces the pill burden; the potential for drug toxicity, drug interaction, or selection of drug-resistant pathogens; and cost. Prophylaxis should be recommenced if the CD4+ T lymphocyte count again decreases to <100–200/μL.


InternalMed_Harrison

InternalMed_Harrison. Individuals who have completed initial therapy for TE should receive treatment indefinitely unless immune reconstitution, with a CD4+ T cell count of >200/μL, occurs as a consequence of cART. Combination therapy with pyrimethamine plus sulfadiazine plus leucovorin is effective for this purpose. An alternative to sulfadiazine in this regimen is clindamycin. Patients receiving secondary prophylaxis for TE are at low risk for recurrence when they have completed initial therapy for TE, remain asymptomatic, and have evidence of restored immune function. Individuals with HIV infection should have a CD4+ T lymphocyte count of >200/μL for at least 6 months after cART. This recommendation is consistent with more extensive data indicating the safety of discontinuing secondary prophylaxis for other opportunistic infections during advanced HIV disease. A repeat MRI brain scan is recommended. Secondary prophylaxis should be reintroduced if the CD4+ T lymphocyte count decreases to <200/μL.


InternalMed_Harrison

InternalMed_Harrison. All HIV-infected persons should be counseled regarding sources of Toxoplasma infection. The chances of primary infection with Toxoplasma can be reduced by not eating undercooked meat and Causes: Asymptomatic infection, acute diarrhea, or chronic diarrhea and malabsorption. Small bowel may demonstrate villous blunting, crypt hypertrophy, and mucosal inflammation. Excystation follows exposure to stomach acid and intestinal proteases, releasing trophozoite forms that multiply by binary fission and reside in the upper small bowel adherent to enterocytes.


InternalMed_Harrison

InternalMed_Harrison. Excystation follows exposure to stomach acid and intestinal proteases, releasing trophozoite forms that multiply by binary fission and reside in the upper small bowel adherent to enterocytes. Cysts and trophozoites are passed in the stool into the environment. Cysts are ingested (10-25 cysts) in contaminated water or food or by direct fecal-oral transmission (as in day-care centers). Encystation occurs under conditions of bile salt concentration changes and alkaline pH. Smooth-walled cysts can contain two trophozoites. Cysts can survive in the environment (up to several weeks in cold water). They may also infect nonhuman mammalian species. FIGuRE 254-1 Life cycle of Giardia. (Reprinted with permission from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, p 987. © 2006, with permission from Elsevier Science.)


InternalMed_Harrison

InternalMed_Harrison. Surface water, ranging from mountain streams to large municipal reservoirs, can become contaminated with fecally derived Giardia cysts. The efficacy of water as a means of transmission is enhanced by the small infectious inoculum of Giardia, the prolonged survival of cysts by avoiding oocyst-contaminated material (i.e., a cat’s litter box). Specifically, lamb, beef, and pork should be cooked to an internal temperature of 165°–170°F; from a more practical perspective, meat cooked until it is no longer pink inside usually satisfies this requirement. Hands should be washed thoroughly after work in the garden, and all fruits and vegetables should be washed. Ingestion of raw shellfish is a risk factor for toxoplasmosis, given that the filter-feeding mechanism of clams and mussels concentrates oocysts. FIGuRE 254-2 Flagellated, binucleate Giardia trophozoites. Protozoal Intestinal Infections and Trichomoniasis Peter F. Weller PROTOZOAL INFECTIONS GIARDIASIS 254


InternalMed_Harrison

InternalMed_Harrison. FIGuRE 254-2 Flagellated, binucleate Giardia trophozoites. Protozoal Intestinal Infections and Trichomoniasis Peter F. Weller PROTOZOAL INFECTIONS GIARDIASIS 254 If the patient owns a cat, the litter box should be cleaned or changed daily, preferably by an HIV-negative, nonpregnant person; alternatively, patients should wash their hands thoroughly after changing the litter box. Litter boxes should be changed daily if possible, as freshly excreted oocysts will not have sporulated and will not be infectious. Patients should be encouraged to keep their cats inside and not to adopt or handle stray cats. Cats should be fed only canned or dried commercial food or well-cooked table food, not raw or undercooked meats. Patients need not be advised to part with their cats or to have their cats tested for toxoplasmosis. Blood intended for transfusion into Toxoplasma-seronegative immunocompromised individuals should be screened for antibody to


InternalMed_Harrison

InternalMed_Harrison. T. gondii. Although such serologic screening is not routinely performed, seronegative women should be screened for evidence of infection several times during pregnancy if they are exposed to environmental conditions that put them at risk for infection with T. gondii. HIV-positive individuals should adhere closely to these preventive measures. Giardia intestinalis (also known as G. lamblia or G. duodena lis) is a cosmopolitan protozoal parasite that inhabits the small intestines of humans and other mammals. Giardiasis is one of the most common parasitic diseases in both developed and developing countries worldwide, causing both endemic and epidemic intestinal disease and diarrhea.


InternalMed_Harrison

InternalMed_Harrison. Life Cycle and Epidemiology (Fig. 254-1) Infection follows the ingestion of environmentally hardy cysts, which excyst in the small intestine, releasing flagellated trophozoites (Fig. 254-2) that multiply by binary fission. Giardia remains a pathogen of the proximal small bowel and does not disseminate hematogenously. Trophozoites remain free in the lumen or attach to the mucosal epithelium by means of a ventral sucking disk. As a trophozoite encounters altered conditions, it forms a morphologically distinct cyst, which is the stage of the parasite usually found in the feces. Trophozoites may be present and even predominate in loose or watery stools, but it is the resistant cyst that survives outside the body and is responsible for transmission. Cysts do not tolerate heating or desiccation, but they do remain viable for months in cold fresh water. The number of cysts excreted varies widely but can approach 107 per gram of stool.


InternalMed_Harrison

InternalMed_Harrison. Ingestion of as few as 10 cysts is sufficient to cause infection in humans. Because cysts are infectious when excreted, person-to-person transmission occurs where fecal hygiene is poor. Giardiasis is especially prevalent in day-care centers; person-to-person spread also takes place in other institutional settings with poor fecal hygiene and during anal-oral contact. If food is contaminated with Giardia cysts after cooking or preparation, food-borne transmission can occur. Waterborne transmission accounts for episodic infections (e.g., in campers and travelers) and for major epidemics in metropolitan areas. 1406 in cold water, and the resistance of cysts to killing by routine chlorination methods that are adequate for controlling bacteria. Viable cysts or filtration. In the United States, Giardia (like


InternalMed_Harrison

InternalMed_Harrison. In the United States, Giardia (like Cryptosporidium; see below) is a com-Isospora -+ + mon cause of waterborne epidemics of Cyclospora -+ + gastroenteritis. Giardia is common in develop-Microsporidia ing countries, and infections may be acquired stains, tissue by travelers.


InternalMed_Harrison

InternalMed_Harrison. There are several recognized genotypes or aO+P, ova and parasites. bNucleic acid amplification tests. assemblages of G. intestinalis. Human infections are due to assemblages A and B, whereas other assemblages are more common in other animals, including cats the stools, and other signs and symptoms of colitis are uncommon and and dogs. Like beavers from reservoirs implicated in epidemics, dogs suggest a different diagnosis or a concomitant illness. Symptoms tend and cats have been found to be infected with assemblages A and B, an to be intermittent yet recurring and gradually debilitating, in contrast observation suggesting that these animals might be sources of human with the acute disabling symptoms associated with many enteric bacteinfection. rial infections. Because of the less severe illness and the propensity for


InternalMed_Harrison

InternalMed_Harrison. Giardiasis, like cryptosporidiosis, creates a significant economic chronic infections, patients may seek medical advice late in the course burden because of the costs incurred in the installation of water of the illness; however, disease can be severe, resulting in malabsorpfiltration systems required to prevent waterborne epidemics, in the tion, weight loss, growth retardation, and dehydration. A number of management of epidemics that involve large communities, and in the extraintestinal manifestations have been described, such as urticaria, evaluation and treatment of endemic infections. anterior uveitis, and arthritis; whether these are caused by giardiasis or concomitant processes is unclear.


InternalMed_Harrison

InternalMed_Harrison. Pathophysiology The reasons that some, but not all, infected patients Giardiasis can be severe in patients with hypogammaglobulinemiadevelop clinical manifestations and the mechanisms by which Giardia and can complicate other preexisting intestinal diseases, such as thatcauses alterations in small-bowel function are largely unknown. occurring in cystic fibrosis. In patients with AIDS, Giardia can causeAlthough trophozoites adhere to the epithelium, they are not invasive enteric illness that is refractory to treatment.


InternalMed_Harrison

InternalMed_Harrison. but may elicit apoptosis of enterocytes, epithelial barrier dysfunction, and epithelial cell malabsorption and secretion. Consequent lactose Diagnosis (Table 254-1) Giardiasis is diagnosed by detection of intolerance and, in a minority of infected adults and children, signifi-parasite antigens in the feces, by identification of cysts in the feces cant malabsorption are clinical signs of the loss of brush-border enzyme or of trophozoites in the feces or small intestines, or by nucleic acid activities. In most infections, the morphology of the bowel is unaltered; amplification tests (NAATs). Cysts are oval, measure 8–12 μm × however, in chronically infected, symptomatic patients, the histopatho-7–10 μm, and characteristically contain four nuclei. Trophozoites are logic findings (including flattened villi) and the clinical manifestations pear-shaped, dorsally convex, flattened parasites with two nuclei and at times resemble those of tropical sprue and gluten-sensitive enteropa-four pairs


InternalMed_Harrison

InternalMed_Harrison. villi) and the clinical manifestations pear-shaped, dorsally convex, flattened parasites with two nuclei and at times resemble those of tropical sprue and gluten-sensitive enteropa-four pairs of flagella (Fig. 254-2). The diagnosis is sometimes difficult thy. The pathogenesis of diarrhea in giardiasis is not known. to establish. Direct examination of fresh or properly preserved stools as


InternalMed_Harrison

InternalMed_Harrison. The natural history of Giardia infection varies markedly. Infections well as concentration methods should be used. Because cyst excretion may be aborted, transient, recurrent, or chronic. G. intestinalis is variable and may be undetectable at times, repeated examination parasites vary genotypically, and such variations might contribute to of stool, sampling of duodenal fluid, and biopsy of the small intestine different courses of infection. Parasite as well as host factors may be may be required to detect the parasite. Tests for parasitic antigens in important in determining the course of infection and disease. Both stool are at least as sensitive and specific as good microscopic examinacellular and humoral responses develop in human infections, but their tions and are easier to perform. Newer NAATs are highly sensitive but precise roles in disease pathogenesis and/or control of infection are are not always available for clinical use at present. unknown. Because patients with


InternalMed_Harrison

InternalMed_Harrison. Newer NAATs are highly sensitive but precise roles in disease pathogenesis and/or control of infection are are not always available for clinical use at present. unknown. Because patients with hypogammaglobulinemia suffer from prolonged, severe infections that are poorly responsive to treatment, humoral immune responses appear to be important. The greater sus-


InternalMed_Harrison

InternalMed_Harrison. Cure rates with metronidazole (250 mg thrice daily for 5 days) are ceptibilities of the young than of the old and of newly exposed persons than of chronically exposed populations suggest that at least partial usually >90%. Tinidazole (2 g once by mouth) may be more effective than metronidazole. Albendazole (400 mg daily for 5–10 days) is as protective immunity may develop. effective as metronidazole and is associated with fewer side effects.


InternalMed_Harrison

InternalMed_Harrison. effective as metronidazole and is associated with fewer side effects. Clinical Manifestations Disease manifestations of giardiasis range from Nitazoxanide (500 mg twice daily for 3 days) is an alternative agent asymptomatic carriage to fulminant diarrhea and malabsorption. Most for treatment of giardiasis. Paromomycin, an oral aminoglycoside infected persons are asymptomatic, but in epidemics the proportion of that is not well absorbed, can be given to symptomatic pregnantsymptomatic cases may be higher. Symptoms may develop suddenly patients, although information is limited on how effectively thisor gradually. In persons with acute giardiasis, symptoms develop after agent eradicates infection.


InternalMed_Harrison

InternalMed_Harrison. an incubation period that lasts at least 5–6 days and usually 1–3 weeks. Almost all patients respond to therapy and are cured, although Prominent early symptoms include diarrhea, abdominal pain, bloating, some with chronic giardiasis experience delayed resolution of sympbelching, flatus, nausea, and vomiting. Although diarrhea is common, toms after eradication of Giardia. For many of the latter patients,upper intestinal manifestations such as nausea, vomiting, bloating, and residual symptoms probably reflect delayed regeneration of intesabdominal pain may predominate. The duration of acute giardiasis is tinal brush-border enzymes. Continued infection should be docuusually >1 week, although diarrhea often subsides. Individuals with mented by stool examinations before treatment is repeated. Patientschronic giardiasis may present with or without having experienced who remain infected after repeated treatments should be evaluated an antecedent acute symptomatic episode. Diarrhea is not


InternalMed_Harrison

InternalMed_Harrison. Patientschronic giardiasis may present with or without having experienced who remain infected after repeated treatments should be evaluated an antecedent acute symptomatic episode. Diarrhea is not necessarily for reinfection through family members, close personal contacts,prominent, but increased flatus, loose stools, sulfurous belching, and and environmental sources as well as for hypogammaglobulinemia.


InternalMed_Harrison

InternalMed_Harrison. (in some instances) weight loss occur. Symptoms may be continual or In cases refractory to multiple treatment courses, prolonged therapyepisodic and may persist for years. Some persons who have relatively with metronidazole (750 mg thrice daily for 21 days) or therapy withmild symptoms for long periods recognize the extent of their discom-varied combinations of multiple agents has been successful.fort only in retrospect. Fever, the presence of blood and/or mucus in Prevention Giardiasis can be prevented by consumption of uncontaminated food and water and by personal hygiene during the provision of care for infected children. Boiling or filtering potentially contaminated water prevents infection.


InternalMed_Harrison

InternalMed_Harrison. The coccidian parasite Cryptosporidium causes diarrheal dis ease that is self-limited in immunocompetent human hosts but can be severe in persons with AIDS or other forms of immunodeficiency. Two species of Cryptosporidium, C. hominis (especially in the United States, sub-Saharan Africa, and Asia) and C. parvum (in Europe), cause most human infections.


InternalMed_Harrison

InternalMed_Harrison. Life Cycle and Epidemiology Cryptosporidium species are widely distributed in the world. Cryptosporidiosis is acquired by the consumption of oocysts (50% infectious dose: ~132 C. parvum oocysts in nonimmune individuals), which excyst to liberate sporozoites that in turn enter and infect intestinal epithelial cells. The parasite’s further development involves both asexual and sexual cycles, which produce forms capable of infecting other epithelial cells and of generating oocysts that are passed in the feces. Cryptosporidium species infect a number of animals, and C. parvum can spread from infected animals to humans. Since oocysts are immediately infectious when passed in feces, person-to-person transmission takes place in day-care centers and among household contacts and medical providers. Waterborne transmission (especially that of C. hominis) accounts for infections in travelers and for common-source epidemics. Oocysts are quite hardy and resist killing by routine chlorination. Both


InternalMed_Harrison

InternalMed_Harrison. Waterborne transmission (especially that of C. hominis) accounts for infections in travelers and for common-source epidemics. Oocysts are quite hardy and resist killing by routine chlorination. Both drinking water and recreational water (e.g., pools, waterslides) have been increasingly recognized as sources of infection.


InternalMed_Harrison

InternalMed_Harrison. Pathophysiology Although intestinal epithelial cells harbor cryptosporidia in an intracellular vacuole, the means by which secretory diarrhea is elicited remain uncertain. No characteristic pathologic changes are found by biopsy. The distribution of infection can be spotty within the principal site of infection, the small bowel. Cryptosporidia are found in the pharynx, stomach, and large bowel of some patients and at times in the respiratory tract. Especially in patients with AIDS, involvement of the biliary tract can cause papillary stenosis, sclerosing cholangitis, or cholecystitis.


InternalMed_Harrison

InternalMed_Harrison. Clinical Manifestations Asymptomatic infections can occur in both immunocompetent and immunocompromised hosts. In immunocompetent persons, symptoms develop after an incubation period of ~1 week and consist principally of watery nonbloody diarrhea, sometimes in conjunction with abdominal pain, nausea, anorexia, fever, and/or weight loss. In these hosts, the illness usually subsides after 1–2 weeks. In contrast, in immunocompromised hosts (especially those with AIDS and CD4+ T cell counts <100/μL), diarrhea can be chronic, persistent, and remarkably profuse, causing clinically significant fluid and electrolyte depletion. Stool volumes may range from 1 to 25 L/d. Weight loss, wasting, and abdominal pain may be severe. Biliary tract involvement can manifest as mid-epigastric or right-upper-quadrant pain.


InternalMed_Harrison

InternalMed_Harrison. Diagnosis (Table 254-1) Evaluation starts with fecal examination for small oocysts, which are smaller (4–5 μm in diameter) than the fecal stages of most other parasites. Because conventional stool examination for ova and parasites (O+P) does not detect Cryptosporidium, specific testing must be requested. Detection is enhanced by evaluation of stools (obtained on multiple days) by several techniques, including modified acid-fast and direct immunofluorescent stains and enzyme immunoassays. Newer NAATs are being employed. Cryptosporidia can also be identified by light and electron microscopy at the apical surfaces of intestinal epithelium from biopsy specimens of the small bowel and, less frequently, the large bowel.


InternalMed_Harrison

InternalMed_Harrison. Nitazoxanide, approved by the U.S. Food and Drug Administration (FDA) for the treatment of cryptosporidiosis, is available in tablet form for adults (500 mg twice daily for 3 days) and as an elixir for children. To date, however, this agent has not been effective for 1407 the treatment of HIV-infected patients, in whom improved immune status due to antiretroviral therapy can lead to amelioration of cryptosporidiosis. Otherwise, treatment includes supportive care with replacement of fluids and electrolytes and administration of antidiarrheal agents. Biliary tract obstruction may require papillotomy or T-tube placement. Prevention requires minimizing exposure to infectious oocysts in human or animal feces. Use of submicron water filters may minimize acquisition of infection from drinking water.


InternalMed_Harrison

InternalMed_Harrison. The coccidian parasite Cystoisospora belli causes human intestinal disease. Infection is acquired by the consumption of oocysts, after which the parasite invades intestinal epithelial cells and undergoes both sexual and asexual cycles of development. Oocysts excreted in stool are not immediately infectious but must undergo further maturation.


InternalMed_Harrison

InternalMed_Harrison. Although C. belli infects many animals, little is known about the epidemiology or prevalence of this parasite in humans. It is most common in tropical and subtropical countries. Acute infections can begin abruptly with fever, abdominal pain, and watery nonbloody diarrhea and can last for weeks or months. In patients who have AIDS or are immunocompromised for other reasons, infections often are not self-limited but rather resemble cryptosporidiosis, with chronic, profuse watery diarrhea. Eosinophilia, which is not found in other enteric protozoan infections, may be detectable. The diagnosis (Table 254-1) is usually made by detection of the large (~25-μm) oocysts in stool by modified acid-fast staining. Oocyst excretion may be low-level and intermittent; if repeated stool examinations are unrevealing, sampling of duodenal contents by aspiration or small-bowel biopsy (often with electron microscopic examination) may be necessary. NAATs are promising newer diagnostic tools.


InternalMed_Harrison

InternalMed_Harrison. Trimethoprim-sulfamethoxazole (TMP-SMX, 160/800 mg four times daily for 10 days; and for HIV-infected patients, then continuing three times daily for 3 weeks) is effective. For patients intolerant of sulfonamides, pyrimethamine (50–75 mg/d) can be used. Relapses can occur in persons with AIDS and necessitate maintenance therapy with TMP-SMX (160/800 mg three times per week).


InternalMed_Harrison

InternalMed_Harrison. Cyclospora cayetanensis, a cause of diarrheal illness, is globally distributed: illness due to C. cayetanensis has been reported in the United States, Asia, Africa, Latin America, and Europe. The epidemiology of this parasite has not yet been fully defined, but waterborne transmission and food-borne transmission (e.g., by basil, sweet peas, and imported raspberries) have been recognized. The full spectrum of illness attributable to Cyclospora has not been delineated. Some infected patients may be without symptoms, but many have diarrhea, flulike symptoms, and flatulence and belching. The illness can be self-limited, can wax and wane, or, in many cases, can involve prolonged diarrhea, anorexia, and upper gastrointestinal symptoms, with sustained fatigue and weight loss in some instances. Diarrheal illness may persist for >1 month. Cyclospora can cause enteric illness in patients infected with HIV.


InternalMed_Harrison

InternalMed_Harrison. The parasite is detectable in epithelial cells of small-bowel biopsy samples and elicits secretory diarrhea by unknown means. The absence of fecal blood and leukocytes indicates that disease due to Cyclospora is not caused by destruction of the small-bowel mucosa. The diagnosis (Table 254-1) can be made by detection of spherical 8to 10-μm oocysts in the stool, although routine stool O+P examinations are not sufficient. Specific fecal examinations must be requested to detect the oocysts, which are variably acid-fast and are fluorescent when viewed with ultraviolet light microscopy. Newer NAATs are proving to be sensitive. Cyclosporiasis should be considered in the differential diagnosis of prolonged diarrhea, with or without a history of travel by the patient to other countries. rare among immunocompetent hosts. In patients with AIDS, intestinal infections with Enterocytozoon bieneusi and Encephalitozoon (formerly


InternalMed_Harrison

InternalMed_Harrison. rare among immunocompetent hosts. In patients with AIDS, intestinal infections with Enterocytozoon bieneusi and Encephalitozoon (formerly Cyclosporiasis is treated with TMP-SMX (160/800 mg twice daily for 7–10 days). HIV-infected patients may experience relapses after such treatment and thus may require longer-term suppressive maintenance therapy.


InternalMed_Harrison

InternalMed_Harrison. Microsporidia are obligate intracellular spore-forming protozoa that infect many animals and cause disease in humans, especially as opportunistic pathogens in AIDS. Microsporidia are members of a distinct phylum, Microspora, which contains dozens of genera and hundreds of species. The various microsporidia are differentiated by their developmental life cycles, ultrastructural features, and molecular taxonomy based on ribosomal RNA. The complex life cycles of the organisms result in the production of infectious spores (Fig. 254-3). Currently, eight genera of microsporidia—Encephalitozoon, Pleistophora, Nosema, Vittaforma, Trachipleistophora, Anncalia, Microsporidium, and Enterocytozoon—are recognized as causes of human disease. Although some microsporidia are probably prevalent causes of self-limited or asymptomatic infections in immunocompetent patients, little is known about how microsporidiosis is acquired.


InternalMed_Harrison

InternalMed_Harrison. Microsporidiosis is most common among patients with AIDS, less common among patients with other types of immunocompromise, and Septata) intestinalis are recognized to contribute to chronic diarrhea and wasting; these infections had been found in 10–40% of patients with chronic diarrhea. Both organisms have been found in the biliary tracts of patients with cholecystitis. E. intestinalis may also disseminate to cause fever, diarrhea, sinusitis, cholangitis, and bronchiolitis. In patients with AIDS, Encephalitozoon hellem has caused superficial keratoconjunctivitis as well as sinusitis, respiratory tract disease, and disseminated infection. Myositis due to Pleistophora has been documented. Nosema, Vittaforma, and Microsporidium have caused stromal keratitis associated with trauma in immunocompetent patients.


InternalMed_Harrison

InternalMed_Harrison. Microsporidia are small gram-positive organisms with mature spores measuring 0.5–2 μm × 1–4 μm. Diagnosis of microsporidial infections in tissue often requires electron microscopy, although intracellular spores can be visualized by light microscopy with hematoxylin and eosin, Giemsa, or tissue Gram’s stain. For the diagnosis of intestinal microsporidiosis, modified trichrome or chromotrope 2R-based staining and Uvitex 2B or calcofluor fluorescent staining reveal spores in smears of feces or duodenal aspirates. Definitive therapies for microsporidial infections remain to be established. For superficial keratoconjunctivitis due to E. hellem, topical therapy with fumagillin suspension has shown promise (Chap. 246e). For enteric infections with E. bieneusi and E. intestinalis in HIV-infected patients, therapy with albendazole may be efficacious (Chap. 246e). Microsporidia Enterocytozoon bieneusi, Encephalitozoon spp., et al.


InternalMed_Harrison

InternalMed_Harrison. Microsporidia Enterocytozoon bieneusi, Encephalitozoon spp., et al. Intracellular multiplication via merogony and sporogony Encephalitozoon intestinalis in epithelial cells, endothelial cells, or macrophages E. bieneusi in epithelial cell Polar tubule pierces host epithelial cell, injects sporoplasm Presumed ingestion or respiratory acquisition of spores Person-to-person, zoonotic, water-borne, or Spore-laden host epithelial cells sloughed into lumina of gastrointestinal, respiratory, or genitourinary tract While E. bieneusi is primarily in the gastrointestinal tract, other species may invade the lung or eye or disseminate to cause: Chronic diarrhea Cholangitis Sinusitis Bronchitis Nephritis Cystitis/prostatitis Keratoconjunctivitis Encephalitis food-borne transmission? Sloughed cells Diagnostic spores present in stool, urine, respiratory fluids, cerebrospinal fluid, or various tissue specimens


InternalMed_Harrison

InternalMed_Harrison. Diagnostic spores present in stool, urine, respiratory fluids, cerebrospinal fluid, or various tissue specimens FIGuRE 254-3 Life cycle of microsporidia. (Reprinted with permission from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, p 1128. © 2006, with permission from Elsevier Science.) Balantidiasis Balantidium coli is a large ciliated protozoal parasite that can produce a spectrum of large-intestinal dis ease analogous to amebiasis. The parasite is widely distributed in the world. Since it infects pigs, cases in humans are more common where pigs are raised. Infective cysts can be transmitted from person to person and through water, but many cases are due to the ingestion of cysts derived from porcine feces in association with slaughtering, with use of pig feces for fertilizer, or with contamination of water supplies by pig feces.


InternalMed_Harrison

InternalMed_Harrison. Ingested cysts liberate trophozoites, which reside and replicate in the large bowel. Many patients remain asymptomatic, but some have persisting intermittent diarrhea, and a few develop more fulminant dysentery. In symptomatic individuals, the pathology in the bowel— both gross and microscopic—is similar to that seen in amebiasis, with varying degrees of mucosal invasion, focal necrosis, and ulceration. Balantidiasis, unlike amebiasis, only rarely spreads hematogenously to other organs. The diagnosis is made by detection of the trophozoite stage in stool or sampled colonic tissue. Tetracycline (500 mg four times daily for 10 days) is an effective therapeutic agent.


InternalMed_Harrison

InternalMed_Harrison. Blastocystosis Blastocystis hominis remains an organism of uncertain pathogenicity. Some patients who pass B. hominis in their stools are asymptomatic, whereas others have diarrhea and associated intestinal symptoms. Diligent evaluation reveals other potential bacterial, viral, or protozoal causes of diarrhea in some but not all patients with symptoms. Because the pathogenicity of B. hominis is uncertain and because therapy for Blastocystis infection is neither specific nor uniformly effective, patients with prominent intestinal symptoms should be fully evaluated for other infectious causes of diarrhea. If diarrheal symptoms associated with Blastocystis are prominent, either metronidazole (750 mg thrice daily for 10 days) or TMP-SMX (160 mg/800 mg twice daily for 7 days) can be used.


InternalMed_Harrison

InternalMed_Harrison. dientamoebiasis Dientamoeba fragilis is unique among intestinal protozoa in that it has a trophozoite stage but not a cyst stage. How trophozoites survive to transmit infection is not known. When symptoms develop in patients with D. fragilis infection, they are generally mild and include intermittent diarrhea, abdominal pain, and anorexia. The diagnosis is made by the detection of trophozoites in stool; the lability of these forms accounts for the greater yield when fecal samples are preserved immediately after collection. Since fecal excretion rates vary, examination of several samples obtained on alternate days increases the rate of detection. Iodoquinol (650 mg three times daily for 20 days) or paromomycin (25–35 mg/kg per day in three doses for 7 days) is appropriate for treatment. Various species of trichomonads can be found in the mouth (in association with periodontitis) and occasionally in the gastrointestinal tract.


InternalMed_Harrison

InternalMed_Harrison. Various species of trichomonads can be found in the mouth (in association with periodontitis) and occasionally in the gastrointestinal tract. Trichomonas vaginalis—one of the most prevalent protozoal parasites 140in the United States—is a pathogen of the genitourinary tract and a major cause of symptomatic vaginitis (Chap. 163). Life Cycle and Epidemiology T. vaginalis is a pear-shaped, actively motile organism that measures about 10 × 7 om, replicates by binary fission, and inhabits the lower genital tract of females and the urethra and prostate of males. In the United States, it accounts for ~3 million infections per year in women. While the organism can survive for a few hours in moist environments and could be acquired by direct contact, person-to-person venereal transmission accounts for virtually all cases of trichomoniasis. Its prevalence is greatest among persons with multiple sexual partners and among those with other sexually transmitted diseases (Chap. 163).


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InternalMed_Harrison. Clinical Manifestations Many men infected with T. vaginalis are asymptomatic, although some develop urethritis and a few have epididymitis or prostatitis. In contrast, infection in women, which has an incubation period of 5–28 days, is usually symptomatic and manifests with malodorous vaginal discharge (often yellow), vulvar erythema and itching, dysuria or urinary frequency (in 30–50% of patients), and dyspareunia. These manifestations, however, do not clearly distinguish trichomoniasis from other types of infectious vaginitis.


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InternalMed_Harrison. diagnosis Detection of motile trichomonads by microscopic examination of wet mounts of vaginal or prostatic secretions has been the conventional means of diagnosis. Although this approach provides an immediate diagnosis, its sensitivity for the detection of T. vaginalis is only ~50–60% in routine evaluations of vaginal secretions. Direct immunofluorescent antibody staining is more sensitive (70–90%) than wet-mount examinations. T. vaginalis can be recovered from the urethra of both males and females and is detectable in males after prostatic massage. A new NAAT, APTIMA, is FDA approved and is highly sensitive and specific for urine and for endocervical and vaginal swabs from women.


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InternalMed_Harrison. Metronidazole (either a single 2-g dose or 500-mg doses twice daily for 7 days) or tinidazole (a single 2-g dose) is effective. All sexual partners must be treated concurrently to prevent reinfection, especially from asymptomatic males. In males with persistent symptomatic urethritis after therapy for nongonococcal urethritis, metronidazole therapy should be considered for possible trichomoniasis. Alternatives to metronidazole for treatment during pregnancy are not readily available. einfection often accounts for apparent treatment failures, but strains of T. vaginalis exhibiting high-level resistance to metronidazole have been encountered. Treatment of these resistant infections with higher oral doses, parenteral doses, or concurrent oral and vaginal doses of metronidazole or with tinidazole has been successful. Introduction to Helminthic Infections Peter F. Weller


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InternalMed_Harrison. Introduction to Helminthic Infections Peter F. Weller The word helminth is derived from the Greek helmins (“parasitic worm”). Helminthic worms are highly prevalent and, depending on the species, may exist as free-living organisms or as parasites of plant or animal hosts. The parasitic helminths have co-evolved with specific mammalian and other host species. Accordingly, most helminthic infections are restricted to nonhuman hosts, and only rarely do these zoonotic helminths accidentally cause human infections.


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InternalMed_Harrison. Helminthic parasites of humans belong to two phyla: Nemathelminthes, which includes nematodes (roundworms), and Platyhelminthes, which includes cestodes (tapeworms) and trematodes (flukes). Helminthic parasites of humans reside within the human body and hence are the cause of true infections. In contrast, parasites of other genera that reside only on mucocutaneous surfaces of humans (e.g., the parasites causing myiasis and scabies) are considered to represent infestations rather than infections.


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InternalMed_Harrison. Helminthic parasites differ substantially from protozoan parasites in several respects. First, protozoan parasites are unicellular organisms, whereas helminthic parasites are multicellular worms that possess differentiated organ systems. Second, helminthic parasites have complex life cycles that require sequential stages of development outside the human host. Thus, most helminths do not complete their replication within the human host; rather, they develop to a certain stage within the mammalian host and, as part of their obligatory life cycle, must mature further outside that host. During the “extra-human” stages of their life cycle, helminths exist either as free-living organisms or as parasites within another host species and thereafter mature into new developmental stages capable of infecting humans. Thus, with only two exceptions (Strongyloides stercoralis and Capillaria philippinensis, which are capable of internal reinfection), increases in the number of adult helminths (i.e.,


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InternalMed_Harrison. humans. Thus, with only two exceptions (Strongyloides stercoralis and Capillaria philippinensis, which are capable of internal reinfection), increases in the number of adult helminths (i.e., the “worm burden”) within the human host require repeated exogenous reinfections. In the case of protozoan parasites, a brief, even singular exposure (e.g., a single mosquito bite transmitting malaria) may lead rapidly to intense parasite loads and overwhelming infections; in contrast, for all but the two helminths noted above, increases in worm burden require multiple and usually ongoing exposures to infectious forms, such as ingestion of eggs of intestinal helminths or waterborne exposures to infectious cercariae of Schistosoma mansoni. This requirement is germane both to the consideration of helminthic infections in individuals and to ongoing global efforts to interrupt and/or minimize the acquisition of helminthic infections by humans.


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InternalMed_Harrison. Third, helminthic infections have a predilection toward stimulation of host immune responses that elicit eosinophilia within human tissues and blood. The many protozoan infections characteristically do not elicit eosinophilia in infected humans, with only three exceptions (two intestinal protozoan parasites, Cystoisospora belli and Dientamoeba fragilis, and tissue-borne Sarcocystis species). The magnitude of helminth-elicited eosinophilia tends to correlate with the extent of tissue invasion by larvae or adult helminths. For example, in several helminthic infections, including acute schistosomiasis (Katayama syndrome), paragonimiasis, and hookworm and Ascaris infections, eosinophilia is most pronounced during the early phases of infection, when migrations of infecting larvae and progression of subsequent developmental stages through the tissues are greatest. In established infections, local eosinophilia is often present around helminths in tissues, but blood eosinophilia may be


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InternalMed_Harrison. of subsequent developmental stages through the tissues are greatest. In established infections, local eosinophilia is often present around helminths in tissues, but blood eosinophilia may be intermittent, mild, or absent. In helminthic infections in which parasites are well contained within tissues (e.g., echinococcal cysts) or confined within the lumen of the intestinal tract (e.g., adult Ascaris or tapeworms), eosinophilia is usually absent.


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InternalMed_Harrison. Nematodes are nonsegmented roundworms. Species of nematodes are remarkably diverse and abundant in nature. Among the many thousands of nematode species, few are parasites of humans. Most nematodes are free-living, and these species have variably evolved to survive in diverse ecologic niches, including saltwater, freshwater, or soil. The well-studied organism Caenorhabditis elegans is a free-living nematode. Nematodes can be either beneficial or deleterious parasites of plants. Parasitic nematodes have co-evolved with specific mammalian hosts and have no capacity to live their full life cycles in other hosts. Uncommonly, humans are exposed to infectious stages of nonhuman nematode parasites, and the resultant zoonotic nematode infections can elicit inflammatory and immune responses as larval forms migrate and die in the unsuitable human host. Examples include pulmonary coin lesions due to mosquito-transmitted infections with the dog heartworm Dirofilaria immitis; eosinophilic


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InternalMed_Harrison. as larval forms migrate and die in the unsuitable human host. Examples include pulmonary coin lesions due to mosquito-transmitted infections with the dog heartworm Dirofilaria immitis; eosinophilic meningoencephalitis due to ingested eggs of the raccoon ascarid Baylisascaris procyonis; and eosinophilic meningitis due to ingestion of larvae of the rat lungworm Angiostrongylus cantonensis.


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InternalMed_Harrison. Nematode parasites of humans include worms that reside in the intestinal tract or localize in extraintestinal vascular or tissue sites. Roundworms are bisexual, with separate male and female forms (except for S. stercoralis, whose adult females are hermaphroditic in the human intestinal tract). Depending on the species, fertilized females release either larvae or eggs containing larvae. Nematodes have five developmental stages: an adult stage and four sequential larval stages. These parasites characteristically are surrounded by a durable outer cuticular layer. Nematodes have a nervous system; a muscular system, including muscle cells under the cuticle; and a developed intestinal tract, including an oral cavity and an elongated gut that ends in an anal pore. Adults may range in size from minute to >1 meter in length (with Dracunculus medinensis, for example, at the long end of this spectrum).


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InternalMed_Harrison. Humans acquire infections with nematode parasites by various routes, depending on the parasitic species. Ingestion of eggs passed in human feces is a major global health problem with many of the intestinal helminths (e.g., Ascaris lumbricoides). In other species, infecting larvae penetrate skin exposed to fecally contaminated soil (e.g., S. stercoralis) or traverse the skin after the bite of infected insect vectors (e.g., filariae). Some nematode infections are acquired by consumption of specific animal-derived foods (e.g., trichinellosis from raw or undercooked pork or wild carnivorous mammals). As noted above, only two nematodes, S. stercoralis and C. philippinensis, can internally reinfect humans.; thus, for all other nematodes, any increases in worm burden must be due to continued exogenous reinfections.


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InternalMed_Harrison. Tapeworms are the cestode parasites of humans. Adult tapeworms are elongated, segmented, hermaphroditic flatworms that reside in the intestinal lumen or, in their larval forms, may live in extraintestinal tissues. Tapeworms include a head (scolex) and a number of attached segments (proglottids). The worms attach to the intestinal tract via their scolices, which may possess suckers, hooks, or grooves. The scolex is the site of formation of new proglottids. Tapeworms do not have a functional gut tract; rather, each tapeworm segment passively and actively obtains nutrients through its specialized surface tegument. Mature proglottids possess both male and female sex organs, but insemination usually occurs between adjacent proglottids. Fertilized proglottids release eggs that are passed in the feces. When ingested by an intermediate host, an egg releases an oncosphere that penetrates the


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InternalMed_Harrison. CHAPTER 255e Introduction to Helminthic Infections gut and develops further in tissues as a cysticercus. Humans acquire infection by ingesting animal tissues that contain cysticerci, and the resultant tapeworms develop and reside in the proximal small bowel (e.g., Taenia solium, T. saginata). Alternatively, if humans ingest eggs of these cestodes that have been passed in human or animal feces, oncospheres develop and can cause space-occupying extraintestinal cystic lesions in tissues; examples include cysticercosis due to T. solium and hydatid disease due to species of Echinococcus.


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InternalMed_Harrison. Trematodes of medical importance include blood flukes, intestinal flukes, and tissue flukes. Adult flukes are often leaf-shaped flatworms. Oral and/or ventral suckers help adult flukes maintain their positions in situ. Flukes have an oral cavity but no distal anal pore. Nutrients are obtained both through their integument and by ingestion into the blind intestinal tract. Flukes are hermaphroditic except for blood flukes (schistosomes), which are bisexual. Eggs are passed in human feces (Fasciola, Fasciolopsis, Clonorchis, Schistosoma japonicum, S. mansoni), urine (S. haematobium), or sputum and feces (Paragonimus). Expelled eggs release miracidia—usually in water—that infect specific snail species. Within snails, parasites multiply and cercariae are released. Depending on the species, cercariae can penetrate the skin (schistosomes) or can develop into metacercariae that can be ingested with plants (e.g., watercress for Fasciola) or with fish (Clonorchis) or crabs (Paragonimus).


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InternalMed_Harrison. Many of the so-called neglected tropical diseases are due to helminthic infections. The health impacts of many helminthic infections are varied and are based on the frequent need for repeated exposures to increase the worm burdens in infected humans. In global regions where exposures to specific helminths occur even in childhood (e.g., fecally derived intestinal nematodes, mosquito-transmitted filariae, or waterborne snail-transmitted schistosome infections), the morbidities in infected individuals can include nutritional, developmental, cognitive, and functional impairments. Ongoing global mass-treatment programs are currently aimed at diminishing the local prevalences of specific helminths and their consequent impacts on the health of local populations.


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InternalMed_Harrison. 1410 ~1 week, female worms release newborn larvae that migrate via the circulation to striated muscle. The larvae of all species except T. pseu- dospiralis, T. papuae, and T. zimbabwensis then encyst by inducing a nematode Infections radical transformation in the muscle cell architecture. Although host Peter F. Weller Nematodes are elongated, symmetric roundworms. Parasitic nematodes of medical significance may be broadly classified as either predominantly intestinal or tissue nematodes. This chapter covers the tissue nematodes that cause trichinellosis, visceral and ocular larva migrans, cutaneous larva migrans, cerebral angiostrongyliasis, and gnathostomiasis. All of these zoonotic infections result from incidental exposure to infectious nematodes. The clinical symptoms of these infections are due largely to invasive larval stages that (except in the case of Trichinella) do not reach maturity in humans.


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InternalMed_Harrison. Trichinellosis develops after the ingestion of meat containing cysts of Trichinella (e.g., pork or other meat from a carnivore). Although most infections are mild and asymptomatic, heavy infections can cause severe enteritis, periorbital edema, myositis, and (infrequently) death. Life Cycle and Epidemiology Eight species of Trichinella are recognized as causes of infection in humans. Two species are distributed worldwide: T. spiralis, which is found in a great variety of carnivorous and omnivorous animals, and T. pseudospiralis, which is found in mammals and birds. T. nativa is present in Arctic regions and infects bears; T. nelsoni is found in equatorial eastern Africa, where it is common among felid predators and scavengers such as hyenas and bush pigs; and T. britovi is found in Europe, western Africa, and western Asia among carnivores but not among domestic swine. T. murrelli is present in North American game animals.


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InternalMed_Harrison. After human consumption of trichinous meat, encysted larvae are liberated by digestive acid and proteases (Fig. 256-1). The larvae invade the small-bowel mucosa and mature into adult worms. After Larvae migrate, penetrate striated muscle, reside in "nurse-cells," and encyst,* causing: Muscle pain, fever, periorbital edema, Larvae are released eosinophilia, occasional in the stomach and mature CNS or cardiac damage in the small bowel, causing: immune responses may help to expel intestinal adult worms, they have few deleterious effects on muscle-dwelling larvae.


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InternalMed_Harrison. Human trichinellosis is often caused by the ingestion of infected pork products and thus can occur in almost any location where the meat of domestic or wild swine is eaten. Human trichinellosis may also be acquired from the meat of other animals, including dogs (in parts of Asia and Africa), horses (in Italy and France), and bears and walruses (in northern regions). Although cattle (being herbivores) are not natural hosts of Trichinella, beef has been implicated in outbreaks when contaminated or adulterated with trichinous pork. Laws that prohibit the feeding of uncooked garbage to pigs have greatly reduced the transmission of trichinellosis in the United States. About 12 cases of trichinellosis are reported annually in this country, but most mild cases probably remain undiagnosed. Recent U.S. and Canadian outbreaks have been attributable to consumption of wild game (especially bear meat) and, less frequently, of pork.


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InternalMed_Harrison. Pathogenesis and Clinical Features Clinical symptoms of trichinellosis arise from the successive phases of parasite enteric invasion, larval migration, and muscle encystment (Fig. 256-1). Most light infections (those with <10 larvae per gram of muscle) are asymptomatic, whereas heavy infections (which can involve >50 larvae per gram of muscle) can be life-threatening. Invasion of the gut by large numbers of parasites occasionally provokes diarrhea during the first week after infection. Abdominal pain, constipation, nausea, or vomiting also may be prominent.


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InternalMed_Harrison. Symptoms due to larval migration and muscle invasion begin to appear in the second week after infection. The migrating Trichinella larvae provoke a marked local and systemic hypersensitivity reaction, with fever and hypereosinophilia. Periorbital and facial edema is common, as are hemorrhages in the subconjunctivae, retina, and nail beds (“splinter” hemorrhages). A maculopapular rash, headache, cough, dyspnea, or dysphagia sometimes develops. Myocarditis with tachyarrhythmias or heart failure—and, less commonly, encephalitis or pneumonitis—may develop and accounts for most deaths of patients with trichinellosis.


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InternalMed_Harrison. Upon onset of larval encystment in muscle 2–3 weeks after infection, symptoms of myositis with myalgias, muscle edema, and weakness develop, usually overlapping with the inflammatory reactions to migrating larvae. The most commonly involved muscle groups include the extraocular muscles; the biceps; and the muscles of the jaw, neck, lower back, and diaphragm. Peaking ~3 weeks after infection, symptoms subside only gradually during a prolonged convalescence. Uncommon infections with T. pseudospiralis, whose larvae do not encapsulate in muscles, elicit prolonged polymyositis-like illness. Laboratory Findings and Diagnosis Blood eosinophilia develops in >90% of patients with symptomatic trichinellosis and may peak at a level of >50% 2–4 weeks after infection. Serum levels of muscle enzymes, including creatine phosphoki-


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InternalMed_Harrison. Encysted larvae ingested Similar cycle (as humans) in undercooked pork, in swine or other carnivores nase, are elevated in most symptomatic patients. boar, horse, or bear (rats, bears, foxes, dogs, or horses) Patients should be questioned thoroughly about their consumption of pork or wild animal meat *T. papuae, T. zimbabwensis, and T. pseudospiralis do not encyst.


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InternalMed_Harrison. and about illness in other individuals who ate FIGuRE 256-1 Life cycle ofTrichinella spiralis (cosmopolitan); nelsoni (equatorial Africa); the same meat. A presumptive clinical diagnosis britovi (Europe, western Africa, western Asia); nativa (Arctic); murrelli (North America); pap-can be based on fevers, eosinophilia, periorbital uae (Papua New Guinea); zimbabwensis (Tanzania); and pseudospiralis (cosmopolitan). CNS, edema, and myalgias after a suspect meal. A rise central nervous system. (Reprinted from RL Guerrant et al [eds]: Tropical Infectious Diseases: in the titer of parasite-specific antibody, which Principles, Pathogens and Practice, 2nd ed, p 1218. © 2006, with permission from Elsevier Science.) usually does not occur until after the third week of infection, confirms the diagnosis. Alternatively, a definitive diagnosis requires surgical biopsy of at least 1 g of involved muscle; the yields are highest near tendon insertions. The fresh muscle tissue should be compressed


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InternalMed_Harrison. Alternatively, a definitive diagnosis requires surgical biopsy of at least 1 g of involved muscle; the yields are highest near tendon insertions. The fresh muscle tissue should be compressed between glass slides and examined microscopically (Fig. 256-2), because larvae may be missed by examination of routine histopathologic sections alone.


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InternalMed_Harrison. FIGuRE 256-2 Trichinella larva encysted in a characteristic hyalinized capsule in striated muscle tissue. (Photo/Wadsworth Center, New York State Department of Health. Reprinted from MMWR 53:606, 2004; public domain.) Most lightly infected patients recover uneventfully with bed rest, antipyretics, and analgesics. Glucocorticoids like prednisone (Table 256-1) are beneficial for severe myositis and myocarditis. Mebendazole and albendazole are active against enteric stages of the parasite, but their efficacy against encysted larvae has not been conclusively demonstrated. Prevention Larvae may be killed by cooking pork until it is no longer pink or by freezing it at -15°C for 3 weeks. However, Arctic T. nativa


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InternalMed_Harrison. Prevention Larvae may be killed by cooking pork until it is no longer pink or by freezing it at -15°C for 3 weeks. However, Arctic T. nativa Trichinellosis Mild Supportive Moderate Albendazole (400 mg bid × 8–14 days) or Mebendazole (200–400 mg tid × 3 days, then 400 mg tid × 8–14 days) Severe Add glucocorticoids (e.g., prednisone, 1 mg/kg qd × 5 days) Visceral larva Mild to Supportive for adults, 400 mg bid for children) with glucocorticoids × 5–20 days has been effective Ivermectin (single dose, 200 μg/kg) or migrans Angiostrongyliasis Mild to Supportive moderate Severe Glucocorticoids (as above) larvae in walrus or bear meat are relatively resistant and may remain 1411 viable despite freezing.


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InternalMed_Harrison. Angiostrongyliasis Mild to Supportive moderate Severe Glucocorticoids (as above) larvae in walrus or bear meat are relatively resistant and may remain 1411 viable despite freezing. Visceral larva migrans is a syndrome caused by nematodes that are normally parasitic for nonhuman host species. In humans, these nematode larvae do not develop into adult worms but instead migrate through host tissues and elicit eosinophilic inflammation. The most common form of visceral larva migrans is toxocariasis due to larvae of the canine ascarid Toxocara canis; the syndrome is due less commonly to the feline ascarid T. cati and even less commonly to the pig ascarid Ascaris suum. Rare cases with eosinophilic meningoencephalitis have been caused by the raccoon ascarid Baylisascaris procyonis.


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InternalMed_Harrison. Life Cycle and Epidemiology The canine roundworm T. canis is distributed among dogs worldwide. Ingestion of infective eggs by dogs is followed by liberation of Toxocara larvae, which penetrate the gut wall and migrate intravascularly into canine tissues, where most remain in a developmentally arrested state. During pregnancy, some larvae resume migration in bitches and infect puppies prenatally (through transplacental transmission) or after birth (through suckling). Thus, in lactating bitches and puppies, larvae return to the intestinal tract and develop into adult worms, which produce eggs that are released in the feces. Eggs must undergo embryonation over several weeks to become infectious. Humans acquire toxocariasis mainly by eating soil contaminated by puppy feces that contains infective T. canis eggs. Visceral larva migrans is most common among children who habitually eat dirt.


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InternalMed_Harrison. Pathogenesis and Clinical Features Clinical disease most commonly afflicts preschool children. After humans ingest Toxocara eggs, the larvae hatch and penetrate the intestinal mucosa, from which they are carried by the circulation to a wide variety of organs and tissues. The larvae invade the liver, lungs, central nervous system (CNS), and other sites, provoking intense local eosinophilic granulomatous responses. The degree of clinical illness depends on larval number and tissue distribution, reinfection, and host immune responses. Most light infections are asymptomatic and may be manifest only by blood eosinophilia. Characteristic symptoms of visceral larva migrans include fever, malaise, anorexia and weight loss, cough, wheezing, and rashes. Hepatosplenomegaly is common. These features may be accompanied by extraordinary peripheral eosinophilia, which may approach 90%. Uncommonly, seizures or behavioral disorders develop. Rare deaths are due to severe neurologic, pneumonic, or


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InternalMed_Harrison. may be accompanied by extraordinary peripheral eosinophilia, which may approach 90%. Uncommonly, seizures or behavioral disorders develop. Rare deaths are due to severe neurologic, pneumonic, or myocardial involvement.


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InternalMed_Harrison. The ocular form of the larva migrans syndrome occurs when Toxocara larvae invade the eye. An eosinophilic granulomatous mass, most commonly in the posterior pole of the retina, develops around the entrapped larva. The retinal lesion can mimic retinoblastoma in appearance, and mistaken diagnosis of the latter condition can lead to unnecessary enucleation. The spectrum of eye involvement also includes endophthalmitis, uveitis, and chorioretinitis. Unilateral visual disturbances, strabismus, and eye pain are the most common presenting symptoms. In contrast to visceral larva migrans, ocular toxocariasis usually develops in older children or young adults with no history of pica; these patients seldom have eosinophilia or visceral manifestations.


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InternalMed_Harrison. Diagnosis In addition to eosinophilia, leukocytosis and hypergammaglobulinemia may be evident. Transient pulmonary infiltrates are apparent on chest x-rays of about one-half of patients with symptoms of pneumonitis. The clinical diagnosis can be confirmed by an enzyme-linked immunosorbent assay for toxocaral antibodies. Stool examination for parasite eggs is worthless in toxocariasis, since the larvae do not develop into egg-producing adults in humans.


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InternalMed_Harrison. The vast majority of Toxocara infections are self-limited and resolve without specific therapy. In patients with severe myocardial, CNS, or pulmonary involvement, glucocorticoids may be employed to reduce inflammatory complications. Available anthelmintic drugs, 1412 including mebendazole and albendazole, have not been shown conclusively to alter the course of larva migrans. Control measures include prohibiting dog excreta in public parks and playgrounds, deworming dogs, and preventing pica in children. Treatment of ocular disease is not fully defined, but the administration of albendazole in conjunction with glucocorticoids has been effective (Table 256-1).


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InternalMed_Harrison. Cutaneous larva migrans (“creeping eruption”) is a serpiginous skin eruption caused by burrowing larvae of animal hookworms, usually the dog and cat hookworm Ancylostoma braziliense. The larvae hatch from eggs passed in dog and cat feces and mature in the soil. Humans become infected after skin contact with soil in areas frequented by dogs and cats, such as areas underneath house porches. Cutaneous larva migrans is prevalent among children and travelers in regions with warm humid climates, including the southeastern United States.


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InternalMed_Harrison. After larvae penetrate the skin, erythematous lesions form along the tortuous tracks of their migration through the dermal-epidermal junction; the larvae advance several centimeters in a day. The intensely pruritic lesions may occur anywhere on the body and can be numerous if the patient has lain on the ground. Vesicles and bullae may form later. The animal hookworm larvae do not mature in humans and, without treatment, will die after an interval ranging from weeks to a couple of months, with resolution of skin lesions. The diagnosis is made on clinical grounds. Skin biopsies only rarely detect diagnostic larvae. Symptoms can be alleviated by ivermectin or albendazole (Table 256-1). Angiostrongylus cantonensis, the rat lungworm, is the most common cause of human eosinophilic meningitis (Fig. 256-3).


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InternalMed_Harrison. Angiostrongylus cantonensis, the rat lungworm, is the most common cause of human eosinophilic meningitis (Fig. 256-3). Southeast Asia and the Pacific Basin but has spread to other areas of the world, including the Caribbean islands, countries in Central and South America, and the southern United States. A. cantonensis larvae produced by adult worms in the rat lung migrate to the gastrointestinal tract and are expelled with the feces. They develop into infective larvae in land snails and slugs. Humans acquire the infection by ingesting raw infected mollusks; vegetables contaminated by mollusk slime; or crabs, freshwater shrimp, and certain marine fish that have themselves eaten infected mollusks. The larvae then migrate to the brain.


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InternalMed_Harrison. Eosinophilic meningitis 2 weeks 3rd-stage larvae (consumed in snail or slime) penetrate gut, go to CNS (then lung in rat) Larvae consumed by land snail/slug (Achatina fulica) viable in fresh water Adult in pulmonary artery produces fertile eggs; larvae hatch, penetrate arterioles, migrate up bronchi, and are coughed up, swallowed, and passed in feces FIGuRE 256-3 Life cycle of Angiostrongylus cantonensis (rat lung worm), found in Southeast Asia, Pacific Islands, Cuba, Australia, Japan, China, Mauritius, and U.S. ports. CNS, central nervous system. (Reprinted from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, p 1225. © 2006, with permission from Elsevier Science.)


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InternalMed_Harrison. Pathogenesis and Clinical Features The parasites eventually die in the CNS, but not before initiating pathologic consequences that, in heavy infections, can result in permanent neurologic sequelae or death. Migrating larvae cause marked local eosinophilic inflammation and hemorrhage, with subsequent necrosis and granuloma formation around dying worms. Clinical symptoms develop 2–35 days after the ingestion of larvae. Patients usually present with an insidious or abrupt excruciating frontal, occipital, or bitemporal headache. Neck stiffness, nausea and vomiting, and paresthesias are also common. Fever, cranial and extraocular nerve palsies, seizures, paralysis, and lethargy are uncommon.


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InternalMed_Harrison. Laboratory Findings Examination of cerebrospinal fluid (CSF) is mandatory in suspected cases and usually reveals an elevated opening pressure, a white blood cell count of 150–2000/μL, and an eosinophilic pleocytosis of >20%. The protein concentration is usually elevated and the glucose level normal. The larvae of A. cantonensis are only rarely seen in CSF. Peripheral-blood eosinophilia may be mild. The diagnosis is generally based on the clinical presentation of eosinophilic meningitis together with a compatible epidemiologic history.


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InternalMed_Harrison. Specific chemotherapy is not of benefit in angiostrongyliasis; larvicidal agents may exacerbate inflammatory brain lesions. Management consists of supportive measures, including the administration of analgesics, sedatives, and—in severe cases—glucocorticoids (Table 256-1). Repeated lumbar punctures with removal of CSF can relieve symptoms. In most patients, cerebral angiostrongyliasis has a self-limited course, and recovery is complete. The infection may be prevented by adequately cooking snails, crabs, and prawns and inspecting vegetables for mollusk infestation. Other parasitic or fungal causes of eosinophilic meningitis in endemic areas may include gnathostomiasis (see below), paragonimiasis (Chap. 259), schistosomiasis (Chap. 259), neurocysticercosis (Chap. 260), and coccidioidomycosis (Chap. 237).


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InternalMed_Harrison. Infection of human tissues with larvae of Gnathostoma spinigerum can cause eosinophilic meningoencephalitis, migratory cutaneous swellings, or invasive masses of the eye and visceral organs.


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InternalMed_Harrison. miasis occurs in many countries and is notably endemic in Southeast Asia and parts of China and Japan. In nature, the mature adult worms parasitize the gastrointestinal tract of dogs and cats. First-stage larvae hatch from eggs passed into water and are ingested by Cyclops species (water fleas). Infective third-stage larvae develop in the flesh of many animal species (including fish, frogs, eels, snakes, chickens, and ducks) that have eaten either infected Cyclops or another infected second intermediate host. Humans typically acquire the infection by eating raw or undercooked fish or poultry. Raw fish dishes, such as som fak in Thailand and sashimi in Japan, account for many cases of human gnathostomiasis. Some cases in Thailand result from the local practice of applying frog or snake flesh as a poultice.


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InternalMed_Harrison. Pathogenesis and Clinical Features Clinical symptoms are due to the aberrant migration of a single larva into cutaneous, visceral, neural, or ocular tissues. After invasion, larval migration may cause local inflammation, with pain, cough, or hematuria accompanied by fever and eosinophilia. Painful, itchy, migratory swellings may develop in the skin, particularly in the distal extremities or periorbital area. Cutaneous swellings usually last ~1 week but often recur intermittently over many years. Larval invasion of the eye can provoke a sight-threatening inflammatory response. Invasion of the CNS results in eosinophilic meningitis with myeloencephalitis, a serious complication due to ascending larval migration along a large nerve track. Patients characteristically present with agonizing radicular pain and paresthesias in the trunk or a limb, which are followed shortly by paraplegia. Cerebral involvement, with focal hemorrhages and tissue destruction, is often fatal.


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InternalMed_Harrison. Diagnosis and Treatment Cutaneous migratory swellings with marked peripheral eosinophilia, supported by an appropriate geographic and dietary history, generally constitute an adequate basis for a clinical diagnosis of gnathostomiasis. However, patients may present with ocular or cerebrospinal involvement without antecedent cutaneous swellings. In the latter case, eosinophilic pleocytosis is demonstrable (usually along with hemorrhagic or xanthochromic CSF), but worms are almost never recovered from CSF. Surgical removal of the parasite from subcutaneous or ocular tissue, though rarely feasible, is both diagnostic and therapeutic. Albendazole or ivermectin may be helpful (Table 256-1). At present, cerebrospinal involvement is managed with supportive measures and generally with a course of glucocorticoids. Gnathostomiasis can be prevented by adequate cooking of fish and poultry in endemic areas. Peter F. Weller, Thomas B. Nutman


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InternalMed_Harrison. Peter F. Weller, Thomas B. Nutman More than a billion persons worldwide are infected with one or more species of intestinal nematodes. Table 257-1 summarizes biologic and clinical features of infections due to the major intestinal parasitic nematodes. These parasites are most common in regions with poor fecal sanitation, particularly in resource-poor countries in the tropics and subtropics, but they have also been seen with increasing frequency among immigrants and refugees to resource-rich countries. Although nematode infections are not usually fatal, they contribute to malnutrition and diminished work capacity. It is interesting that these helminth infections may protect some individuals from allergic disease. Humans may on occasion be infected with nematode parasites that ordinarily infect animals; these zoonotic infections produce diseases such as trichostrongyliasis, anisakiasis, capillariasis, and abdominal angiostrongyliasis.


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InternalMed_Harrison. Intestinal nematodes are roundworms; they range in length from 1 mm to many centimeters when mature (Table 257-1). Their life cycles are complex and highly varied; some species, including Strongyloides stercoralis and Enterobius vermicularis, can be transmitted directly from person to person, while others, such as Ascaris lumbricoides, Necator americanus, and Ancylostoma duodenale, require a soil phase for development. Because most helminth parasites do not self-replicate, the acquisition of a heavy burden of adult worms requires repeated exposure to the parasite in its infectious stage, whether larva or egg. Hence, clinical disease, as opposed to asymptomatic infection, generally develops only with prolonged residence in an endemic area and is typically related to infection intensity. In persons with marginal nutrition, intestinal helminth infections may impair growth and development. Eosinophilia and elevated serum IgE levels are features of many helminth infections and, when


InternalMed_Harrison

InternalMed_Harrison. In persons with marginal nutrition, intestinal helminth infections may impair growth and development. Eosinophilia and elevated serum IgE levels are features of many helminth infections and, when unexplained, should always prompt a search for intestinal helminths. Significant protective immunity to intestinal nematodes appears not to develop in humans, although mechanisms of parasite immune evasion and host immune responses to these infections have not been elucidated in detail.


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InternalMed_Harrison. A. lumbricoides is the largest intestinal nematode parasite of humans, reaching up to 40 cm in length. Most infected individuals have low worm burdens and are asymptomatic. Clinical disease arises from 1413 larval migration in the lungs or effects of the adult worms in the intestines.


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InternalMed_Harrison. Life Cycle Adult worms live in the lumen of the small intestine. Mature female Ascaris worms are extraordinarily fecund, each producing up to 240,000 eggs a day, which pass with the feces. Ascarid eggs, which are remarkably resistant to environmental stresses, become infective after several weeks of maturation in the soil and can remain infective for years. After infective eggs are swallowed, larvae hatched in the intestine invade the mucosa, migrate through the circulation to the lungs, break into the alveoli, ascend the bronchial tree, and return— through swallowing—to the small intestine, where they develop into adult worms. Between 2 and 3 months elapse between initial infection and egg production. Adult worms live for 1–2 years.


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InternalMed_Harrison. Epidemiology Ascaris is widely distributed in tropical and subtropical regions as well as in other humid areas, including the rural southeastern United States. Transmission typically occurs through fecally contaminated soil and is due either to a lack of sanitary facilities or to the use of human feces as fertilizer. With their propensity for hand-to-mouth fecal carriage, younger children are most affected. Infection outside endemic areas, though uncommon, can occur when eggs on transported vegetables are ingested.


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InternalMed_Harrison. Clinical Features During the lung phase of larval migration, ~9–12 days after egg ingestion, patients may develop an irritating nonproductive cough and burning substernal discomfort that is aggravated by coughing or deep inspiration. Dyspnea and blood-tinged sputum are less common. Fever is usually reported. Eosinophilia develops during this symptomatic phase and subsides slowly over weeks. Chest x-rays may reveal evidence of eosinophilic pneumonitis (Löffler’s syndrome), with rounded infiltrates a few millimeters to several centimeters in size. These infiltrates may be transient and intermittent, clearing after several weeks. Where there is seasonal transmission of the parasite, seasonal pneumonitis with eosinophilia may develop in previously infected and sensitized hosts.


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InternalMed_Harrison. In established infections, adult worms in the small intestine usually cause no symptoms. In heavy infections, particularly in children, a large bolus of entangled worms can cause pain and small-bowel obstruction, sometimes complicated by perforation, intussusception, or volvulus. Single worms may cause disease when they migrate into aberrant sites. A large worm can enter and occlude the biliary tree, causing biliary colic, cholecystitis, cholangitis, pancreatitis, or (rarely) intrahepatic abscesses. Migration of an adult worm up the esophagus can provoke coughing and oral expulsion of the worm. In highly endemic areas, intestinal and biliary ascariasis can rival acute appendicitis and gallstones as causes of surgical acute abdomen.


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InternalMed_Harrison. Laboratory Findings Most cases of ascariasis can be diagnosed by microscopic detection of characteristic Ascaris eggs (65 by 45 μm) in fecal samples. Occasionally, patients present after passing an adult worm— identifiable by its large size and smooth cream-colored surface—in the stool or, much less commonly, through the mouth or nose. During the early transpulmonary migratory phase, when eosinophilic pneumonitis occurs, larvae can be found in sputum or gastric aspirates before diagnostic eggs appear in the stool. The eosinophilia that is prominent during this early stage usually decreases to minimal levels in established infection. Adult worms may be visualized, occasionally serendipitously, on contrast studies of the gastrointestinal tract. A plain abdominal film may reveal masses of worms in gas-filled loops of bowel in patients with intestinal obstruction. Pancreaticobiliary worms can be detected by ultrasound and endoscopic retrograde cholangiopancreatography; the latter method


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InternalMed_Harrison. in gas-filled loops of bowel in patients with intestinal obstruction. Pancreaticobiliary worms can be detected by ultrasound and endoscopic retrograde cholangiopancreatography; the latter method also has been used to extract biliary Ascaris worms.


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InternalMed_Harrison. Ascariasis should always be treated to prevent potentially serious complications. Albendazole (400 mg once), mebendazole (100 g twice daily for 3 days or 500 mg once), or ivermectin (150–200 μg/kg aTime from infection to egg production by mature female worm. once) is effective. These medications are contraindicated in pregnancy, however. Mild diarrhea and abdominal pain are uncommon side effects of these agents. Partial intestinal obstruction should be managed with nasogastric suction, IV fluid administration, and instillation of piperazine through the nasogastric tube, but complete obstruction and its severe complications require immediate surgical intervention.


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InternalMed_Harrison. Two hookworm species (A. duodenale and N. americanus) are responsible for human infections. Most infected individuals are asymptomatic. Hookworm disease develops from a combination of factors—a heavy worm burden, a prolonged duration of infection, and an inadequate iron intake—and results in iron-deficiency anemia and, on occasion, hypoproteinemia.


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InternalMed_Harrison. Life Cycle Adult hookworms, which are ~1 cm long, use buccal teeth (Ancylostoma) or cutting plates (Necator) to attach to the small-bowel mucosa and suck blood (0.2 mL/d per Ancylostoma adult) and interstitial fluid. The adult hookworms produce thousands of eggs daily. The eggs are deposited with feces in soil, where rhabditiform larvae hatch and develop over a 1-week period into infectious filariform larvae. Infective larvae penetrate the skin and reach the lungs by way of the bloodstream. There they invade alveoli and ascend the airways before being swallowed and reaching the small intestine. The prepatent period from skin invasion to appearance of eggs in the feces is ~6–8 weeks, but it may be longer with A. duodenale. Larvae of A. duodenale, if swallowed, can survive and develop directly in the intestinal mucosa. Adult hookworms may survive over a decade but usually live ~6–8 years for A. duodenale and 2–5 years for N. americanus. Hot, humid regions Worldwide Worldwide


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InternalMed_Harrison. Hot, humid regions Worldwide Worldwide Small-bowel mucosa Cecum, colonic Cecum, appendix mucosa Decades (owing to 5 years 2 months autoinfection) 5000–10,000 3000–7000 2000 Epidemiology A. duodenale is prevalent in southern Europe, North Africa, and northern Asia, and N. americanus is the predominant species in the Western Hemisphere and equatorial Africa. The two species overlap in many tropical regions, particularly Southeast Asia. In most areas, older children have the highest incidence and greatest intensity of hookworm infection. In rural areas where fields are fertilized with human feces, older working adults also may be heavily infected.


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InternalMed_Harrison. Clinical Features Most hookworm infections are asymptomatic. Infective larvae may provoke pruritic maculopapular dermatitis (“ground itch”) at the site of skin penetration as well as serpiginous tracks of subcutaneous migration (similar to those of cutaneous larva migrans; Chap. 256) in previously sensitized hosts. Larvae migrating through the lungs occasionally cause mild transient pneumonitis, but this condition develops less frequently in hookworm infection than in ascariasis. In the early intestinal phase, infected persons may develop epigastric pain (often with postprandial accentuation), inflammatory diarrhea, or other abdominal symptoms accompanied by eosinophilia. The major consequence of chronic hookworm infection is iron deficiency. Symptoms are minimal if iron intake is adequate, but marginally nourished individuals develop symptoms of progressive iron-deficiency anemia and hypoproteinemia, including weakness and shortness of breath.


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InternalMed_Harrison. Laboratory Findings The diagnosis is established by the finding of characteristic 40by 60-μm oval hookworm eggs in the feces. Stool-concentration procedures may be required to detect light infections. Eggs of the two species are indistinguishable by light microscopy. In a stool sample that is not fresh, the eggs may have hatched to release rhabditiform larvae, which need to be differentiated from those of S. stercoralis. Hypochromic microcytic anemia, occasionally with eosinophilia or hypoalbuminemia, is characteristic of hookworm disease.


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InternalMed_Harrison. Hookworm infection can be eradicated with several safe and highly effective anthelmintic drugs, including albendazole (400 mg once) and mebendazole (500 mg once). Mild iron-deficiency anemia can often be treated with oral iron alone. Severe hookworm disease with protein loss and malabsorption necessitates nutritional support and oral iron replacement along with deworming. There is some concern that the benzimidazoles (mebendazole and albendazole) are becoming less effective against human hookworms.


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InternalMed_Harrison. Ancylostoma caninum and Ancylostoma braziliense A. caninum, the canine hookworm, has been identified as a cause of human eosinophilic enteritis, especially in northeastern Australia. In this zoonotic infection, adult hookworms attach to the small intestine (where they may be visualized by endoscopy) and elicit abdominal pain and intense local eosinophilia. Treatment with mebendazole (100 mg twice daily for 3 days) or albendazole (400 mg once) or endoscopic removal is effective. Both of these animal hookworm species can cause cutaneous larva migrans (“creeping eruption”; Chap. 256).


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InternalMed_Harrison. S. stercoralis is distinguished by its ability—unique among helminths (except for Capillaria; see below)—to replicate in the human host. This capacity permits ongoing cycles of autoinfection as infective larvae are internally produced. Strongyloidiasis can thus persist for decades without further exposure of the host to exogenous infective larvae. In immunocompromised hosts, large numbers of invasive Strongyloides larvae can disseminate widely and can be fatal.


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InternalMed_Harrison. Life Cycle In addition to a parasitic cycle of development, Strongyloides can undergo a free-living cycle of development in the soil (Fig. 257-1). This adaptability facilitates the parasite’s survival in the absence of mammalian hosts. Rhabditiform larvae passed in feces can transform into infectious filariform larvae either directly or after a free-living phase of development. Humans acquire strongyloidiasis when filariform larvae in fecally contaminated soil penetrate the skin or mucous membranes. The larvae then travel through the bloodstream to the lungs, where they break into the alveolar spaces, ascend the bronchial tree, are swallowed, and thereby reach the small intestine. There the larvae mature into adult worms that penetrate the mucosa of the proximal small bowel. The minute (2-mm-long) parasitic adult female worms reproduce by parthenogenesis; adult males do not exist. Eggs hatch in the intestinal mucosa, releasing rhabditiform larvae that migrate to the lumen and pass


InternalMed_Harrison

InternalMed_Harrison. (2-mm-long) parasitic adult female worms reproduce by parthenogenesis; adult males do not exist. Eggs hatch in the intestinal mucosa, releasing rhabditiform larvae that migrate to the lumen and pass with the feces into soil. Alternatively, rhabditiform larvae in the bowel can develop directly into filariform larvae that penetrate the colonic wall or perianal skin and enter the circulation to repeat the migration that establishes ongoing internal reinfection. This autoinfection cycle allows strongyloidiasis to persist for decades.


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InternalMed_Harrison. Epidemiology S. stercoralis is spottily dis tributed in tropical areas and other hot, cutaneous and/or abdominal symptoms. Recurrent urticaria, often 1415 involving the buttocks and wrists, is the most common cutaneous manifestation. Migrating larvae can elicit a pathognomonic serpiginous eruption, larva currens (“running larva”). This pruritic, raised, erythematous lesion advances as rapidly as 10 cm/h along the course of larval migration. Adult parasites burrow into the duodenojejunal mucosa and can cause abdominal (usually midepigastric) pain, which resembles peptic ulcer pain except that it is aggravated by food ingestion. Nausea, diarrhea, gastrointestinal bleeding, mild chronic colitis, and weight loss can occur. Small-bowel obstruction may develop with early, heavy infection. Pulmonary symptoms are rare in uncomplicated strongyloidiasis. Eosinophilia is common, with levels fluctuating over time.


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InternalMed_Harrison. The ongoing autoinfection cycle of strongyloidiasis is normally constrained by unknown factors of the host’s immune system. Abrogation of host immunity, especially with glucocorticoid therapy and much less commonly with other immunosuppressive medications, leads to hyperinfection, with the generation of large numbers of filariform larvae. Colitis, enteritis, or malabsorption may develop. In disseminated strongyloidiasis, larvae may invade not only gastrointestinal tissues and the lungs but also the central nervous system, peritoneum, liver, and kidneys. Moreover, bacteremia may develop because of the passage of enteric flora through disrupted mucosal barriers. Gram-negative sepsis, pneumonia, or meningitis may complicate or dominate the clinical course. Eosinophilia is often absent in severely infected patients. Disseminated strongyloidiasis, particularly in patients with unsuspected infection who are given glucocorticoids, can be fatal. Strongyloidiasis is a frequent complication of


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InternalMed_Harrison. infected patients. Disseminated strongyloidiasis, particularly in patients with unsuspected infection who are given glucocorticoids, can be fatal. Strongyloidiasis is a frequent complication of infection with human


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InternalMed_Harrison. Intestinal Nematode InfectionsCHAPTER 2572-mm hermaphroditic adult s penetrate small-bowel mucosa and release eggs, which hatch to rhabditiform larvae. Larvae shed in stool Lung or intestinal stage may cause: Eosinophilia and intermittent epigastric pain Autoinfection: Transform within the intestine into filariform larvae, which penetrate perianal skin or bowel mucosa, causing: Pruritic larva currens Eosinophilia Hyperinfection: With immunosuppression, larger Larvae migrate via bloodstream or lymphatics to lungs, ascend airway to trachea and pharynx, and are swallowed. T cell lymphotropic virus type 1, but disseminated strongyloidiasis is not common among patients infected with HIV-1.


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InternalMed_Harrison. T cell lymphotropic virus type 1, but disseminated strongyloidiasis is not common among patients infected with HIV-1. Free-living 1-mm adults in soil Eggs in soil Indirect development (heterogonic) (can multiply outside host for several generations) in soil Direct development Rhabditiform larvae in soil numbers of filariform larvae develop, penetrate bowel, and disseminate, causing: Colitis, polymicrobial sepsis, pneumonitis, or meningitis humid regions and is particularly common in Southeast Asia, sub-Saharan Africa, and Brazil. In the United States, the parasite is endemic in parts of the Southeast and is found in immigrants, refugees, travelers, and military personnel who have lived in endemic areas.


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InternalMed_Harrison. FIGuRE 257-1 Life cycle of Strongyloides stercoralis. (Adapted from Guerrant RL et al Clinical Features In uncomplicated strongyloidia-[eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, p 1276. © 2006, sis, many patients are asymptomatic or have mild with permission from Elsevier Science.) 1416 Diagnosis In uncomplicated strongyloidiasis, the finding of rhabditiform larvae in feces is diagnostic. Rhabditiform larvae are ~250 μm long, with a short buccal cavity that distinguishes them from hookworm larvae. In uncomplicated infections, few larvae are passed and single stool examinations detect only about one-third of cases. Serial examinations and the use of the agar plate detection method improve the sensitivity of stool diagnosis. In uncomplicated strongyloidiasis (but not in hyperinfection), stool examinations may be repeatedly negative. Strongyloides larvae may also be found by sampling of the duodenojejunal contents by aspiration or biopsy. An


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InternalMed_Harrison. (but not in hyperinfection), stool examinations may be repeatedly negative. Strongyloides larvae may also be found by sampling of the duodenojejunal contents by aspiration or biopsy. An enzyme-linked immunosorbent assay for serum antibodies to antigens of Strongyloides is a sensitive method for diagnosing uncomplicated infections. Such serologic testing should be performed for patients whose geographic histories indicate potential exposure, especially those who exhibit eosinophilia and/or are candidates for glucocorticoid treatment of other conditions. In disseminated strongyloidiasis, filariform larvae should be sought in stool as well as in samples obtained from sites of potential larval migration, including sputum, bronchoalveolar lavage fluid, or surgical drainage fluid.


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InternalMed_Harrison. Even in the asymptomatic state, strongyloidiasis must be treated because of the potential for subsequent dissemination and fatal hyperinfection. Ivermectin (200 μg/kg daily for 2 days) is consistently more effective than albendazole (400 mg daily for 3 days). For disseminated strongyloidiasis, treatment with ivermectin should be extended for at least 5–7 days or until the parasites have been eradicated. In immunocompromised hosts, the course of ivermectin should be repeated 2 weeks after initial treatment. Most infections with Trichuris trichiura are asymptomatic, but heavy infections may cause gastrointestinal symptoms. Like the other soil-transmitted helminths, whipworm is distributed globally in the tropics and subtropics and is most common among poor children from resource-poor regions of the world.


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InternalMed_Harrison. Life Cycle Adult Trichuris worms reside in the colon and cecum, the anterior portions threaded into the superficial mucosa. Thousands of eggs laid daily by adult female worms pass with the feces and mature in the soil. After ingestion, infective eggs hatch in the duodenum, releasing larvae that mature before migrating to the large bowel. The entire cycle takes ~3 months, and adult worms may live for several years. Clinical Features Tissue reactions to Trichuris are mild. Most infected individuals have no symptoms or eosinophilia. Heavy infections may result in anemia, abdominal pain, anorexia, and bloody or mucoid diarrhea resembling inflammatory bowel disease. Rectal prolapse can result from massive infections in children, who often suffer from malnourishment and other diarrheal illnesses. Moderately heavy Trichuris burdens also contribute to growth retardation.


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InternalMed_Harrison. Diagnosis and Treatment The characteristic 50by 20-μm lemon-shaped Trichuris eggs are readily detected on stool examination. Adult worms, which are 3–5 cm long, are occasionally seen on proctoscopy. Mebendazole (500 mg once) or albendazole (400 mg daily for 3 doses) is safe and moderately effective for treatment, with cure rates of 70–90%. Ivermectin (200 μg/kg daily for 3 doses) is also safe but is not quite as efficacious as the benzimidazoles. E. vermicularis is more common in temperate countries than in the tropics. In the United States, ~40 million persons are infected with pinworms, with a disproportionate number of cases among children.


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InternalMed_Harrison. Life Cycle and Epidemiology Enterobius adult worms are ~1 cm long and dwell in the cecum. Gravid female worms migrate nocturnally into the perianal region and release up to 2000 immature eggs each. The eggs become infective within hours and are transmitted by hand-to-mouth passage. From ingested eggs, larvae hatch and mature into adults. This life cycle takes ~1 month, and adult worms survive for ~2 months. Self-infection results from perianal scratching and transport of infective eggs on the hands or under the nails to the mouth. Because of the ease of person-to-person spread, pinworm infections are common among family members.


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InternalMed_Harrison. Clinical Features Most pinworm infections are asymptomatic. Perianal pruritus is the cardinal symptom. The itching, which is often worse at night as a result of the nocturnal migration of the female worms, may lead to excoriation and bacterial superinfection. Heavy infections have been alleged to cause abdominal pain and weight loss. On rare occasions, pinworms invade the female genital tract, causing vulvovaginitis and pelvic or peritoneal granulomas. Eosinophilia is uncommon. Diagnosis Since pinworm eggs are not released in feces, the diagnosis cannot be made by conventional fecal ova and parasite tests. Instead, eggs are detected by the application of clear cellulose acetate tape to the perianal region in the morning. After the tape is transferred to a slide, microscopic examination will detect pinworm eggs, which are oval, measure 55 by 25 μm, and are flattened along one side.


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InternalMed_Harrison. Infected children and adults should be treated with mebendazole (100 mg once) or albendazole (400 mg once), with the same treatment repeated after 2 weeks. Treatment of household members is advocated to eliminate asymptomatic reservoirs of potential reinfection. Trichostrongylus species, which are normally parasites of herbivo rous animals, occasionally infect humans, particularly in Asia and Africa. Humans acquire the infection by accidentally ingesting Trichostrongylus larvae on contaminated leafy vegetables. The larvae do not migrate in humans but mature directly into adult worms in the small bowel. These worms ingest far less blood than hookworms; most infected persons are asymptomatic, but heavy infections may give rise to mild anemia and eosinophilia. In stool examinations, Trichostrongylus eggs resemble hookworm eggs but are larger (85 by 115 μm). Treatment consists of mebendazole or albendazole (Chap. 246e).