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Host to an intruder

      Presentation

      A 44-year-old homeless man with AIDS had a 3-week history of watery diarrhea accompanied by minimal mid-epigastric abdominal pain and cramping. He reported that he had more than 10 large-volume stools daily, and the diarrhea was most severe when he attempted to eat. Recently, he had begun to get light-headed when he rose from a seated position, and on one occasion, he fainted.
      The patient had also lost 40 pounds since he had last been weighed. He had no nausea, vomiting, or blood in his stools, and he denied fevers, chills, night sweats, mental status changes, or neurologic symptoms. None of his contacts were ill, and he had not traveled outside Baltimore.
      HIV infection was most likely contracted through intravenous (IV) drug use. While the patient said that he no longer used IV drugs, he continued to smoke heroin on a daily basis. He denied homosexual contact and was not sexually active. His last CD4 cell count was 8 cells/mm3. In the past, he had been treated for Pneumocystis carinii pneumonia, latent syphilis, and disseminated herpes zoster infection. Currently, he was taking no medications.

      Assessment

      On physical examination, the patient was mildly somnolent and cachectic. While lying flat, his blood pressure was 120/62 mm Hg with a pulse rate of 53 bpm. When he stood, his blood pressure dropped to 100/50 mm Hg, and his pulse rate rose to 87 bpm. An oral examination disclosed dry mucous membranes and thrush. He had temporal muscle wasting and lanugo hair. His neck was supple, and he had no lymphadenopathy or rashes. Cardiovascular and pulmonary examinations were normal.
      The patient’s abdomen was soft with normal bowel sounds and no tenderness, distention, masses, or splenomegaly. His liver span was 12 cm to percussion, and it was palpable 4 cm below the right costal margin. A rectal examination revealed no masses or fissures. His stool was brown, and a hemoccult test proved negative. Aside from the aforementioned somnolence, his neurologic examination was normal.
      Initial laboratory studies placed the patient’s white blood cell count at 950 cells/mm3 with a differential of 8% polymorphonucleocytes, 60% lymphocytes, 28% monocytes, and 4% eosinophils. His platelet count was 396 000 cells/mm3 and the hematocrit was 35.6%. Levels of potassium (3.5 mEq/L), bicarbonate (22 mEq/L), blood urea nitrogen (11 mg/dL), and creatinine (0.6 mg/dL) were also measured. Liver function test results were within the normal range. A serum Cryptococcus neoformans antigen test was positive. The patient’s stool was evaluated for ova and parasites (Figure).
      Figure thumbnail gr1
      Figure 1A trichrome stain of the stool specimen (100X) shows a teardrop-shaped trophozoite with 2 identical nuclei, a feature that is typical of this organism.

      Diagnosis

      The patient was diagnosed with cryptococcal meningitis, and subsequently treated for this illness, but the symptoms that brought him into the emergency department were caused by Giardia lamblia infection. G. lamblia, which is also known as G. intestinalis or G. duodenalis, was one of the earliest protozoans identified microscopically by van Leeuwenhoek in 1681; it was more definitively described by Lamb in 1859.
      • Dobell C.
      The discovery of the intestinal protozoa of man.
      Initially thought to be a commensal organism in man, G. lamblia is now known to be a major cause of infectious diarrhea with millions affected worldwide. In the United States, almost 5000 people are hospitalized each year for complications of Giardia-induced diarrhea, making it the most common parasitic source of diarrhea.
      • Lee S.H.
      • Levy D.A.
      • Craun G.F.
      • Beach M.J.
      • Calderon R.L.
      Surveillance for waterborne-disease outbreaks—United States, 1999-2000.
      Giardia infection is much more widespread in developing countries, although most infections are asymptomatic. For example, seroprevalence studies show that 40% of children in Peru are infected prior to 6 months of age.
      • Miotti P.G.
      • Gilman R.H.
      • Santosham M.
      • Ryder R.W.
      • Yolken R.H.
      Age-related seropositivity and antibody to Giardia lamblia in four diverse populations.
      G. lamblia is a eukaryotic protozoan and the only species of Giardia known to infect mammalian species. It is found in a wide variety of domesticated and wild animals, including dogs, cats, and beavers. The organism’s life cycle consists of an infectious cyst and an active form or trophozoite. Infection can follow the ingestion of as few as 10 cysts.
      • Rendtorff R.C.
      The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules.
      Once swallowed and exposed to the gastric pH and pancreatic proteases, excystation takes place, producing up to 2 trophozoites.
      The trophozoites then reproduce asexually by binary fission in the duodenum and upper jejunum, becoming encysted again in the ileum and colon.
      • Plorde J.J.
      Flagellates.
      On microscopic examination, the cysts appear small and round to oval in shape with 4 nuclei. This is the form primarily seen on stool examination. However, in our patient, the trophozoite was evident, resembling a teardrop when viewed from the dorsal or ventral aspect (Figure).
      • Ortega Y.R.
      • Adam R.D.
      Giardia overview and update.
      Also visible in the figure are the 2 genetically identical nuclei. Four flagellae (not visible) extend from the paramedian bodies, providing the tumbling motility characteristic of G. lamblia. A ventral disk acts as a suction cup, allowing for attachment to the mucosal surface.
      • Ortega Y.R.
      • Adam R.D.
      Giardia overview and update.
      G. lamblia can survive in fresh water for periods of up to 2 months, and it is resistant to chlorination.
      • deReignier D.P.
      • Cole L.
      • Schupp D.G.
      • Erlandsen S.L.
      Viability of Giardia cysts suspended in lake, river, and tap water.
      • Jarroll E.L.
      • Bingham A.K.
      • Meyer E.A.
      Effect of chlorine on Giardia lamblia cyst viability.
      Transmission occurs by many routes, including ingestion of contaminated food and water, direct fecal-oral contact such as has been reported in day care centers, and through anal intercourse.
      • Osterholm M.T.
      • Forfang J.C.
      • Ristinen T.L.
      • et al.
      An outbreak of foodborne giardiasis.
      • Thompson S.C.
      Giardia lamblia in children and the child care setting a review of the literature.
      • Meyers J.D.
      • Kuharic H.A.
      • Holmes K.K.
      Giardia lamblia infection inhomosexual men.
      Most people infected with G. lamblia are asymptomatic. This is particularly true of people living in endemic areas—travelers who are infected after visiting these locations are more likely to experience symptoms. Among those who do develop symptoms, the incubation period is usually 1 to 2 weeks, but it can be as long as 45 days.
      • Ortega Y.R.
      • Adam R.D.
      Giardia overview and update.
      The most common complaints are abdominal cramping, flatulence, bloating, anorexia, and weight loss. Diarrhea is generally described as loose and foul-smelling with increased amounts of mucous and fat. Blood is not present in the stool. Symptoms tend to be prolonged, and patients often endure them for 1 to 2 weeks before seeking medical evaluation.
      • Ortega Y.R.
      • Adam R.D.
      Giardia overview and update.
      Physical findings are nonspecific. Malabsorption is frequently reported and may affect a variety of nutrients. The most common malabsorptive syndrome associated with Giardia infection is lactose intolerance; lactase deficiency is noted in 20% to 40% of cases.
      • Hill D.R.
      Giardiasis Issues in diagnosis and management.
      G. Lamblia is not an opportunistic pathogen, and infection does not seem to have a more severe or prolonged course in patients with HIV infection. Nevertheless, a clustering of cases observed in some areas has been linked to homosexual transmission in an AIDS population.
      • Esfandiari A.
      • Swartz J.
      • Teklehaimanot S.
      Clustering of giardiosis among AIDS patients in Los Angeles County.
      Historically, diagnosis of giardiasis has most commonly been accomplished via microscopic examination of a stool sample for cysts or less frequently, for trophozoites. Trichrome or iron hematoxylin stains are useful in this endeavor. Keep in mind that examination of one stool sample will yield a detection rate of only 60% to 80%, while evaluating up to 3 stool samples increases the yield to over 90%.
      • Hiatt R.A.
      • Markell E.K.
      • Ng E.
      How many stool examinations are necessary to detect pathogenic intestinal protozoa?.
      More recently, detection of Giardia antigen in the stool has been performed using a number of approaches, including enzyme-linked immunosorbent assays, nonenzymatic immunoassays, or fluoroscein-tagged monoclonal antibodies. With these techniques, the sensitivity and specificity for detection of Giardia in a single stool specimen are both greater than 90%.
      • Aldeen W.E.
      • Carroll K.
      • Robison A.
      • Morrison M.
      • Hale D.
      Comparison of nine commercially available enzyme-linked immunosorbent assays for the detection of Giardia lamblia in fecal specimens.
      • Garcia L.S.
      • Shimizu R.Y.
      Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens.
      However, in many situations, stool examination for ova and parasites remains necessary to evaluate for other types of parasitic infection. More invasive means of testing for Giardia include sampling of duodenal contents with the string test or duodenal aspiration and biopsy using esophagogastroduodenoscopy. This may be necessary in cases where repeated stool testing is negative, but malabsorptive diarrhea continues.
      • Ortega Y.R.
      • Adam R.D.
      Giardia overview and update.

      Management

      The treatment of choice for Giardia infection is metronidazole, which fatally damages trophozoite DNA.
      • Gardner T.B.
      • Hill D.R.
      Treatment of Giardiasis.
      It is most commonly prescribed in a regimen of 250 mg by mouth 2 or 3 times daily for 5 to 10 days. This results in a median efficacy of 92%.
      • Gardner T.B.
      • Hill D.R.
      Treatment of Giardiasis.
      In December 2004, tinidazole, another member of the nitroimidazole class of antiprotozoal drugs, was approved for use in the United States. The recommended dosage for the treatment of giardiasis is 2 gm by mouth one time. Two other agents, onidazole and secnidazole, are not available in this country.
      At one time, the antimalarial drug quinacrine was used to treat giardiasis, but cases of life-threatening hemolysis and psychosis have been reported. Multiple other medications have also been used to effectively treat giardiasis including furazolidone, albendazole, paromomycin, and bacitracin zinc.
      • Gardner T.B.
      • Hill D.R.
      Treatment of Giardiasis.
      Aside from drug therapy for cryptococcal meningitis, our patient was prescribed a 10-day regimen of oral metronidazole and a lactose-free diet. His gastrointestinal symptoms resolved completely. The source of his G. lamblia infection was unknown, and he was lost to follow-up after his discharge.

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