Immunological Testing for Occult Blood in Acute Infectious Diarrhea
ABSTRACT & COMMENTARY
Synopsis: According to the authors, a modified guaiac test can replace microscopic stool examination to distinguish between inflammatory and non-inflammatory diarrhea.
Source: Beltinger J, et al. Immunological testing for occult blood in patients with acute infectious diarrhea. Can it improve the specificity of the guaiac test? Dig Dis Sciences 1997;42:366-371.
Aprospective study was performed at the dhaka hospital of the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh. In 304 patientsmostly childrenclinical presentation, stool microscopy, stool culture, and modified guaiac test were recorded. Stool microscopy and guaiac test were compared in the differentiation between inflammatory (Shigella, Salmonella) and non-inflammatory (V. cholera, no pathogens detected) diarrheal cases. The sensitivity of the guaiac test was 69% as compared to 63-67% for stool microscopy. Specificity improved from 60% to 75% by using a more complex latex agglutination test for the immunological detection of occult blood (Colo-Immun-Test).
Beltinger et al conclude that a modified guaiac test can replace microscopic stool examination to distinguish between inflammatory and non-inflammatory diarrhea; because of its simplicity, it may be especially useful for community health workers in the diagnostic work-up of acute infectious diarrhea.
COMMENT BY JAY S. KEYSTONE, MD, MSc
The above study confirms the results of previous investigations of occult blood compared with fecal leukocytes in the diagnosis of inflammatory bacterial diarrhea. In a similar recently published study, medical students at Tulane University and University of Texas evaluated, in Guadalajara, Mexico, the effectiveness of fecal occult blood as a screening test for invasive bacterial pathogens and as a substitute for the fecal leukocyte examination in adult and pediatric cases of acute diarrhea.1 The adult subjects in this retrospective data analysis consisted of 889 of 925 college students from the United States who developed diarrhea while attending the University of San Diego or University of Arizona summer programs in Guadalajara, Mexico, and who had their diarrheal stools tested for leukocytes, occult blood, and enteric pathogens over a five-year period from 1988 to 1992. In another study, the stools of 151 Mexican children between 3 months and 7 years of age were evaluated as a part of a clinical trial in Guadalajara, Mexico, during the summer of 1985.
In both studies, pretreatment stools were submitted to a laboratory for enteric pathogens; fecal occult blood was sought using a commercial test kit. In adult studies, fecal leukocytes were detected by trichrome staining and in the pediatric study by methylene blue staining. For the fecal leukocyte test, 20 high-power microscopic fields were examined per specimen for a total of five minutes. To be positive, five or more leukocytes had to be identified in a majority of fields.
Data analysis revealed that occult blood negative samples were reliable indicators of a lack of invasive bacterial infections in both adult and pediatric patients (negative predictive values of 87% and 95%, respectively). Positive results for either test were not reliably predictive as indicators of invasive bacteria among adults. In pediatric patients, a positive occult blood test was significantly more sensitive than a positive fecal leukocyte test result (79% vs 41%) in detecting invasive bacteria; however, the positive predictive value was only 24%. In the adult population, the positive occult blood test showed a similar but low sensitivity compared with the fecal leukocyte test result (42% and 57%, respectively) in detecting invasive bacteria. When either test was considered, the sensitivity rose to 67% and 79% in the adult and pediatric populations, respectively.
The authors point out that the fecal occult blood test is an uncomplicated, low-cost test that is reliable when it is negative, indicating a lack of invasive bacteria in adult and pediatric patients with diarrhea. In children, a positive result on fecal occult blood test is sensitive but not specific in detecting invasive bacterial enteropathogens. These data also indicate that a commercially available test for occult blood represents a suitable alternative to microscopic examination of fecal samples for leukocytes obtained from patients with acute diarrhea.
Traditionally in acute infectious diarrhea, the standard screening procedure for invasive bacterial pathogens has been fecal leukocyte detection.2-4 Since invasive bacterial pathogens produce not only intestinal inflammation, but also mucosal hemorrhage and often dysentery, a test of fecal occult blood should be indicative of an invasive pathogen. Knowing whether a patient with traveler’s diarrhea is infected with an "invasive pathogen" has two advantages. It will guide the clinician in determining whether or not a bacterial culture is indicated and assist in the decision as to the need for antibiotic therapy. Although the institution of antibiotics is most often dependent upon the patient’s degree of illness, in these days of managed care, any cost savings that might be accrued from not carrying out bacterial cultures could be a significant advantage to a medical practitioner. In this study, the authors showed that fecal occult blood was an appropriate test to rule out invasive pathogens such as Shigella sp., Salmonella sp., or Campylobacter jejuni. The specificity and negative predictive values of microscopic fecal leukocytes and fecal occult blood as screening procedures for invasive bacteria compared with culture were high, indicating that a negative result in either was generally accurate. However, neither test was particularly sensitive, and both had low positive predictive values. The authors point out that "in a clinic where adult patients with a high frequency of bacterial diarrhea are commonly evaluated, patients with a negative test result without fever may not require further evaluation. Adult patients with a positive occult blood test result may be further studied with stool culturing, and those with fever may be regarded as possible candidates for antimicrobial therapy."
The sensitivity of the occult blood testing in the pediatric population was nearly double that of the fecal leukocyte test, suggesting that occult blood testing may be used as a substitute for fecal leukocyte examination and could be a viable alternative in situations where microscopic evaluation and bacterial cultures are unavailable.
Compared with standard fecal leukocyte examination, occult blood testing is cheaper and easier to perform. The test might have particular applicability in developing countries where bacterial culture is often unavailable, even in the most severely ill cases. The study by Beltinger et al from Bangladesh showed that screening stools for occult blood may be used to identify patients with invasive bacterial diarrhea in other areas of the world.
Another technique that has recently been employed to determine whether or not stools should be cultured for enteric pathogens is the fecal lactoferrin screening test for inflammatory bacterial diarrhea developed by Guerrant and colleagues at the University of Virginia School of Medicine. Lactoferrin is a glycoprotein that is present in polymorphonuclear neutrophil granules and is not found in lymphocytes or monocytes. A simple agglutination assay for lactoferrin as a marker for fecal leukocytes was tested on 55 samples from 46 patients with diarrhea and nine controls without diarrhea seen at Fairfax Hospital, VA. Of the 28 samples with Salmonella, Shigella, or Campylobacter infection, 93% had detectable fecal lactoferrin while 83% of 18 samples with rotavirus and all nine controls without diarrhea were negative at a titer of 1:50. Studies performed at the University of Virginia have shown that using fecal leukocyte detection with freshly obtained specimens to select those for culture can increase the yield of positive results by as much as five fold, with a simultaneous reduction in the cost per positive culture from $1000 to $150.5
Huicho et al recently carried out a meta-analysis of fecal screening tests in the approach to acute infectious diarrhea.6 They concluded that fecal lactoferrin was the most accurate index test. Fecal leukocytes showed the lowest performance as assessed by the area under the curve. Occult blood and combination of fecal leukocytes with clinical data yielded intermediate curves. The greater sensitivity of fecal lactoferrin over fecal leukocytes by microscopy for invasive diarrhea has been shown in several studies. Scerpella et al found that 94% and 69% of travelers with invasive pathogens had elevated fecal lactoferrin and fecal leukocytes, respectively.7 Fecal leukocytes detected by methylene microscopy were found in only 40% of C. difficile toxin-positive fecal specimens compared with a 75% positive detection rate for the fecal lactoferrin assay.8 Thornton and colleagues examined fecal specimens from Shigella-infected U.S. troops participating in operation Restore Hope in Somalia and noted that the "Leuko-Test" for fecal lactoferrin (Tech Lab Inc. Blacksburg, VA) was positive in 88% of infected patients compared with 63% positivity for fecal leukocytes detected by microscopy.9 It was interesting to note that 33% of 21 specimens positive for fecal lactoferrin and negative by culture were PCR-positive for Shigella sp.
The above studies indicate that occult blood, fecal leukocytes, and fecal lactoferrin can be very useful indicators of invasive enteric pathogens and the need to perform bacterial cultures on patients with diarrhea illness. Further prospective studies are required to determine which screening test provides the greatest information for the least cost.
References
1. McNeely WS, et al. Occult blood versus fecal leukocytes in the diagnosis of bacterial diarrhea: A study of U.S. travelers to Mexico and Mexican children. Am J Trop Med Hyg 1996;55:430-433.
2. Harris JC, et al. Fecal leukocytes in diarrheal illness. Ann Intern Med 1972;76:696-703.
3. Guerrant RL, et al. Evaluation and diagnosis of acute infectious diarrhea. Am J Med 1985;78:91-98.
4. Korzeniowski OM, et al. Value of examination for fecal leukocytes in the early diagnosis of shigellosis. Am J Trop Med Hyg 1979;28:1031-1035.
5. Choi SW, et al. To culture or not to culture: Fecal lactoferrin screening for inflammatory bacterial diarrhea. J Clin Micro 1996;34:928-932.
6. Huicho L, et al. Fecal screening tests in the approach to acute infectious diarrhea: a scientific overview. Ped Infect Dis 1996;15:486-494.
7. Scerpella EG, et al. Evaluation of a new latex agglutination test for fecal lactoferrin in Travelers’ diarrhea. J Trav Med 1994;1:4-7.
8. Yong WH, et al. Comparison of fecal lactoferrin latex agglutination assay and methylene blue microscopy for detection of fecal leukocytes in Clostridium difficile-associated disease. J Clin Microbiol 1994;2:1360-1361.
9. Thornton S, et al. Evaluation of a rapid latex test for detection of lactoferrin in stool. C-397, p 560 in Abstracts of the 94th General Meeting of the American Society of Microbiology 1994. American Society for Microbiology, Washington, DC.
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