Bradley A. Connor

Pathologic Changes in the Small Bowel in Nine Patients with Diarrhea Associated with a Coccidia-like Body

In recent years, a novel intestinal organism has been noted in the stools of patients with a syndrome characterized by prolonged diarrhea associated with fatigue and anorexia [1-5]. The organism resembles either a cyanobacterium or a coccidian and has been called a cyanobacteria-like or coccidia-like body (CLB) [6]. A recent report suggested that the organism is a coccidian, and the name Cyclospora cayetanensis was proposed [7]. Until the taxonomic issues are definitively resolved, we refer to the organism as CLB. The Canadian International Water and Energy Consultants (CIWEC) Clinic in Kathmandu, Nepal, first noted the organism in June 1989. Fifty-five cases were subsequently documented that year in an outbreak that ended 4 months later [4]. From May to October 1990, another outbreak was documented, with a total of 86 cases. One hundred four cases were diagnosed in 1991, yielding a total of 245 cases seen at the CIWEC Clinic in three distinct outbreaks (Figure 1). All patients had diarrhea, fatigue, and anorexia. The illness lasted an average of 42 days and was refractory to various antibiotic treatments. All patients recovered completely. The organism has yet to be discovered in the stools of an asymptomatic patient. Figure 1. The number of new cases infected with coccidia-like bodies per week, defined as the date of the first positive stool specimen for each patient. The illness is almost invariably associated with weight loss and malabsorption of d-33ylose. Many patients also experience nausea, but tenesmus and signs of dysentery are absent. For these reasons, the infection was hypothesized to occur in the upper intestine. We conducted a study to evaluate this possibility by doing upper gastrointestinal endoscopy with duodenal aspiration and small-bowel biopsy in patients infected with CLB. Methods Background The CIWEC Clinic, an outpatient facility that serves the expatriate and tourist populations in Kathmandu, Nepal, treats 5000 patients per year, of whom 30% have a diarrheal complaint. Because endoscopy is not routinely available, we arranged for an American board-certified gastroenterologist to visit the clinic for 1 week during the predicted height of the outbreak in June 1991. Microbiology The CLB organism can be observed in plain smears of the stool of infected patients. The organism is spherical and is 9 to 10min width. The organism can be concentrated by flotation in Sheather sucrose solution or by centrifugation of a formalin-ether preparation of stool [8]. The organism stains variably red with the modified acid-fast stain used to identify cryptosporidium (Figure 2). All stools submitted for examination to the CIWEC Clinic were screened for the presence of this organism. When CLB was identified, stools were also screened for the presence of ova or parasites, blood, or leukocytes. Bacteriologic and viral studies are not routinely done at our clinic. During the 1991 outbreak, we arranged for a limited number of CLB-positive stools to undergo bacteriologic and virologic studies via the Armed Forces Research Institute of Medical Science in Bangkok, Thailand. Six of the nine patients with CLB who underwent endoscopy had bacteriologic screening for enteric pathogens, using standard culture techniques and DNA probes of prepared stool blots on filter paper [9]. The other three patients could not be screened in this fashion because of logistic difficulties. Of 95 other patients with CLB, 33 had similar studies done during the course of the summer. The specimens were screened for rotavirus using a commercially available enzyme-linked immunosorbent assay (ELISA) test [10]. Figure 2. Oil immersion photograph of smear of concentrated stool specimen of patient with chronic diarrhea. Selection of Patients and Controls Thirty-four patients had been identified as having diarrhea associated with CLB before the gastroenterologist arrived in Nepal (12 June 1991). Of these 34 patients, 9 were still infected with CLB, were available in Kathmandu, and were willing to have upper endoscopy during the week that the endoscopist was available. Seven persons without diarrhea and without CLB in their stools were recruited as controls. Of these, four were completely asymptomatic and three had requested upper endoscopy because of preexisting upper gastrointestinal symptoms. Informed consent was obtained from all persons having endoscopy. Endoscopic Procedure Upper gastrointestinal endoscopy was done in all patients by the same gastroenterologist after a fast of at least 6 hours in every case. Topical anesthesia was achieved using dyclonine gargle before each procedure. Using the Olympus XQ20 or Olympus XP20 fiberoptic gastroscope (Olympus Corp., Lake Success, New York), endoscopic examination to the descending duodenum was done in all patients. Endoscopic assessment of the esophagus, stomach, and duodenum was made. Duodenal fluid was aspirated into sterile specimen traps using a sterile saline irrigation of the duodenal bulb and descending duodenum. At least two forceps biopsy specimens of the distal duodenum were obtained in each case. Biopsy specimens were preserved in 10% neutral buffered formalin for light microscopy and in 200 mol/L formalin glutaraldehyde for electron microscopy. Examination of Endoscopically Obtained Material Duodenal aspirates were examined immediately by light microscopy without stain and after staining with the modified acid-fast stain. The aspirates were preserved at 4 C for up to 1 week and were then transported at ambient temperature to New York where they were cultured for acid-fast bacteria using Lowenstein-Jensen and American Trudeau Society media. Duodenal biopsy specimens from cases and controls were examined in a blinded fashion by pathologists from two separate New York institutions. Duodenal biopsy specimens for light and electron microscopy were fixed and prepared as previously described [11]. d-Xylose Absorption Test Three patients with CLB had d-xylose absorption tests. Twenty-five grams of d-xylose were administered to patients after an overnight fast. Urine was collected for 5 hours. The amount of d-xylose in the urine was calculated using a standard photometric method. Case Report The nine patients with CLB had similar clinical histories. All symptoms resolved spontaneously in 2 to 12 weeks. The following case report is representative. A 40-year-old Canadian woman who had resided in Nepal since October 1990 developed watery diarrhea with urgency on 15 May 1991. She was 7 weeks postpartum at the time and was breast-feeding her infant son. The diarrhea persisted for 3 days with about five loose stools per day. She started taking nalidixic acid on the first day of illness. A stool examination on 16 May showed only a few ascaris eggs, for which she was given mebendazole. She was healthy from 18 May to 22 May, at which time she noted the return of diarrhea and fatigue. The symptoms of anorexia, fatigue, and nausea tended to occur simultaneously, but intermittently, during the ensuing weeks. On 23 May 1991, a stool specimen submitted to the CIWEC Clinic was positive for the presence of CLBs. Repeated stool examinations on 28 May and 4 June were unchanged. On 10 June, examination showed few CLBs, and on 12 June and 17 June, rare CLBs were reported. Ad-xylose absorption test was done on 18 June. A total of 0.9 g of d-xylose was excreted in the 5-hour urine collection (3.6% of the loading dose; normal, >20%). An upper gastrointestinal endoscopy was done on 17 June 1991. The patients esophagus and stomach were normal; however, mild erythema of the duodenal bulb and marked erythema of the distal duodenum were noted. Symptoms persisted, and a repeated stool examination on 21 June showed rare CLBs. A stool examination was done on 28 June while she was still feeling ill. Results were negative for CLB; her symptoms resolved steadily during the next 7 days, and she has remained well. Results Patient Data We studied six men and three women. Four were tourists, and five were foreign residents of Nepal. Their mean age was 36 6 years (range, 22 to 48 years), and their mean length of time in Nepal was 405 391 days (range, 21 to 1460 days). Symptoms were present in patients with CLB from 4 to 53 days before endoscopy. The mean age of the seven non-CLB controls was 33 6 years (range, 25 to 42 years). The mean length of time in Nepal for controls was 917 727 days (range, 60 to 2920 days). Clinical Features The predominant symptoms in the nine patients with CLB were diarrhea and fatigue. Crampy abdominal pain was present in some, but not all, of the patients and varied in intensity. Two patients reported a subjective fever at the onset of their illness. Nausea was variably present in all but two patients studied. Eructation or flatulence was also common. Weight loss, estimated at 5% to 10% of body weight, was reported by all patients and appeared to increase with the duration of symptoms. Microbiology Six patients with CLB who had biopsies had bacteriologic cultures done on their stool specimens. Three results were negative, two were positive for enterotoxigenic Escherichia coli, and one was positive for enterohemorrhagic E. coli. None of these six patients had rotavirus antigen in their stools. Thirty-three of 95 other CLB-positive patients had the same bacteriologic studies done in 1991. Of these 33 patients, 2 tested positive for enterotoxigenic E. coli, and 1 each for Shigella flexnerii and Shigella boydii. The overall rate of bacterial infection in the CLB-positive patients was 7 of 39 (18%). d-Xylose Testing Three patients had d-xylose absorption tests. The amount of urinary excretion of d-xylose in a 5-hour urine collection for the three patients was 0.9 g (3.6%), 1.3 g (5.2%), and 2.4 g (9.6%), respectively. Expected values are 5 g or more ( 20%). Endoscopic Findings Of the nine patients with CLB, five had moderate to marked erythema of the distal duodenum. None of the seven controls had distal duo

Cyclosporiasis: Clinical and Histopathologic Correlates

Although the histopathologic changes associated with Cyclospora cayetanensis infection have been previously described, the histopathology and the appearance of various life cycle stages have not been correlated with severity, stage, and duration of clinical disease. We report a prospective clinical investigation of disease characteristics and histopathologic findings in three otherwise healthy, immunocompetent patients with symptomatic C. cayetanensis infection, the duration of which ranged from 6 to 60 days. Varying degrees of gross and microscopic gastrointestinal inflammation were seen before treatment. An electron-dense phospholipid membrane/myelin-like material was variably present both before and after treatment. The greatest amount of myelin-like material was seen in the patient with prolonged disease. The results of our study suggest that inflammatory changes associated with C. cayetanensis infection may persist beyond parasite eradication. It is intriguing to speculate that the myelin-like material is a marker for persistent inflammation, but further study and confirmation are needed.

Chronic Diarrhea in Travelers

As a rule, travelers’ diarrhea is a self-limited bacterial infection that affects approximately 40 % of travelers to developing countries. Health-care professionals who see returning travelers have noted that some travelers afflicted with diarrhea do not recover completely but, instead, develop chronic diarrhea or a persistent change in gastrointestinal function. Concurrent with this observation has been the recognition that in many patients with long-standing irritable bowel syndrome, an episode of traveler’s diarrhea or gastroenteritis preceded the onset of symptoms. Before a diagnosis of postinfectious irritable bowel syndrome is considered, other diagnostic considerations must be excluded. This review will examine an approach to the patient with chronic diarrhea posttravel.

Multiplex PCR testing for travelers’ diarrhea—friend or foe?

Abstract With the advent of high throughput multiplex DNA extraction PCR diagnostic modalities for the diagnosis of infectious diseases, particularly gastrointestinal enteric infections, the increased sensitivity and specificity of this modality has been hailed by most as an advance in our ability to make specific etiologic diagnoses in acute and chronic gastroenteritis and travelers diarrhea.(Platts-Mills et al., 2012; Raich and Powell, 2014) The potential advantages and drawbacks of this modality of testing are illustrated by the following case.

Pulmonary edema in malaria

A 33-year-old Australian woman, who had been stationed in Liberia for 4 months, flew to New York City for vacation. Several days later, she developed fever, rigors, lower back pain, and headache. On the third day of symptoms, she was acutely ill and was admitted to The New York Hospital where a peripheral blood smear showed characteristic ring forms of Pfalciparum (Figure 1). She had discontinued chloroquine and proguanil prophylaxis due to gastrointestinal intolerance 10 weeks before admission. Initial laboratory studies included white blood cell (WBC) count of 4800/mm3; hemoglobin, 11.9 g/dL; hematocrit, 34%; platelet count, 43,000/mm3; lactic dehydrogenase (LDH), 399 IU; prothrombin time (PT), 14.7 seconds (control 12.0 s); and partial thromboplastin time m, 35.1 seconds (control 38 s). Admission chest examination and roentgenogram were normal (Figure 2, A). After 18 hours of treatment with oral quinine and doxycycline, parasitemia was reduced from 2. IL to 1.2%. However, 12 hours later, the patient developed acute respiratory distress with severe hypoxemia (arterial PO, 38 mmHg breathing room air). Bronchial breath sounds and rales were heard over both lower lung fields. Fever to 39°C persisted, although parasitemia was less than 0.1%. The patient developed evidence suggesting coagulopathy or disseminated intravascular coagulation (DIG) with a further increase in PT to15.4 seconds and a positive D-dimer test. Repeat chest x-ray was consistent with