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The Use of the Unstimulated Nitroblue Tetrazolium Test as a Routine Screening Test for Bacterial Infection in an Adult Population: A Reassessment STEPHEN J. BITTNER, M.D., ELLIOTT K I E F F , M.D., DOROTHY WINDHORST, M.D., AND PAUL MEIER, P H . D . University of Chicago, Departments of Medicine and Statistics, Chicago, Illinois ABSTRACT Bittner, Stephen J., Kieff, Elliott, Windhorst, Dorothy, and Meier, Paul: The use of the unstimulated nitroblue tetrazolium test as a routine screening test for bacterial infection in an adult population: A reassessment. Am. J. Clin. Pathol. 60: 843-853, 1973. A simplified version of the unstimulated nitroblue tetrazolium (NBT) test potentially adaptable for routine general hospital use was devised and employed to study 141 subjects in four population groups: healthy adults, patients with bacterial infection, patients with nonbacterial infection, and patients with noninfectious illness. There was no distinct segregation of patients with bacterial infections from patients with other disease processes. The NBT test failed to correlate with the underlying diagnosis in 27% of the subjects studied. T h e method of Park et al16 was employed simultaneously in 45 subjects and the two methods were found to have comparable accuracy of discrimination. T h e NBT test was also compared with erythrocyte sedimentation rate, pyrexia, and neutrophilia as indices for discriminating bacterial infection from other disease and found to be the least discriminatory single test. T h e unstimulated NBT test may be somewhat useful as an adjunct to other indices in diagnosing bacterial infection, but it is not appropriate for the routine laboratories of acute general hospitals. PARK ET AL.16 first demonstrated that the mean proportion of neutrophils capable of spontaneous reduction of nitroblue Received April 9, 1973; received revised manuscript June 1, 1973; accepted for publication June 4, 1973. Supported in part by U. S. Public Health Training Grant 1 T01 AI00449-01 from NIAID. Presented in part at the November 1, 1972 meeting of the Central Society for Clinical Research. Address reprint requests to: Dr. Elliott Kieff, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637. 843 tetrazolium dye in vitro was significantly elevated in 25 pediatric patients with acute bacterial infection and four with candidemia. T h e test clearly differentiated these from 30 healthy controls and 65 patients with other disease processes: rheumatoid arthritis, systemic lupus erythematosus, viral infections, mumps encephalitis, and primary tuberculosis. Since the initial study, prospective and retrospective series have found it to be useful as an adjunct to 844 A.J.C.P.—Vol. 60 BITTNER ET AL. Table 1. Patient Population Studied and Test Values Condition I. Bacterial infections UTI with bacteremia UTI without bacteremia Pneumonia No. of Subjects No. of Tests 5 3 5 3 15 16 %NBT©PMN 8.5 13 13 3.75 4 12.25 5.25 6 0.25 9.25 2.5 7 3 1.75 42 10.25 22.5 6.5 0.5 19.5 10.25 10.25 15 Carcinomatosis with bacteremia 5 5 1 Intra-abdominal abscess 4 4 10.5 Osteomyelitis 2 2 12 Septic abortion 2 2 2.75 20 Suppurating leg ulcers 2 2 18.5 10.5 Intracranial abscess, endometritis, septic thrombophlebitis, lung abscess, tertiary syphilis, gastroenteritis secondary to post-antibiotic overgrowth 1 each (6) 9.25 0.75 0 3.75 0 0.75 12 13 0.5 1 each 32.25 (6) 16 53.5 4.5 Meningitis 3 3 5.5 Bacterial endocarditis 4 4 33.5 51 52 Infectious mononucleosis Herpes zoster Guillain-Barre syndrome Viral URI Viral gastroenteritis Aseptic meningitis Infectious hepatitis 1 2 2 2 1 1 1 2 2 2 2 Pneumocystis carinii pneumonia 1 5.25 Active pulmonary tuberculosis 1 7 Malaria 1 7.75 Systemic candidosis 1 2 Chronic mucocutaneous candidosis 1 2 15 17 5 7 7 Rule out immune deficiency 3 4 Psoriasis 5 5 Rheumatoid arthritis 4 4 0.5 Carcinomatosis 3 3 1 4.5 Systemic lupus erythematosus 3 3 7 7 Profound nutritional anemia 2 2 0 2.5 2 2 17 2.5 1.25 26 9.5 11.5 3.25 0.75 13.5 64 Non-bacterial infections Viral: III. Noninfectious illnesses Ulcerative colitis Fibrinous pericarditis Asthmatic attack Thrombophlebitis 1 each (24) 7 4 2.5 2.75 4 3.75 7.5 7.5 1 1.75 2.75 4.5 7 6.25 21 3.5 12 4.5 8 6.5 2.5 1 12.5 1 each 9 (24) 7.5 1.5 4.5 3.5 17 6.5 1 4.25 1.75 16.75 December 1973 845 UNSTIMULATED NBT TEST Table Condition 1.—(Continued) No. of Subjects No. of Tests %NBT0PMN 2.5 Cerebrovascular accident Disseminated intravascular coagulation 2° to ruptured ectopic pregnancy Congestive heart failure Sarcoidosis Erythema nodosum Idiopathic thrombocytopenia Penicillin drug reaction Transfusion reaction Myasthenia gravis Mycosis fungoides Eczema Polymyalgia rheumatica Scrotal dermatitis—aseptic Allergic granulomatous vasculitis Sickle-cell anemia crisis Pleural effusion—aseptic Brown-Sequard syndrome Leg ulcer Osteomalcia—vitamin D deficiency Galactorrhea—? etiology Cholelithiasis Hypothyroidism 4 5.25 6.5 4.75 0.25 64 10 2.25 0.5 1.5 8.5 0 39.5 0 6 1 11.25 2 0 2.5 0.5 51 54 IV. Normal controls 24 29 the differentiation of bacterial infection from other febrile conditions and infections in adults as well as children. 6 " 1 0 1 2 1 3 1 8 2 1 In the one evaluation of the test in a large adult series, 12 94% of the subjects with bacterial infection had elevated proportions of NBT-positive neutrophils (NBTSPMN's), while in a group of 18 controls and 84 patients with nonbacterial illness all but one had normal NBT tests. As the result of this and other studies, the NBT test has been recommended as a routine test for general service laboratories. 11 There have, however, been many procedural modifications of the original test, and the extent to which these modifications affect the reliability of the test has not been determined in comparative studies. Furthermore, there is a growing number of clinical situations in which the results of the NBT test are not concordant with the underlying diagnosis, and many of the affirmative studies exaggerate the discriminatory ability of the test.6,8-21 We report here the results of a study of the usefulness of the NBT test in deciding whether moderately to severely ill adult patients admitted to an acute general hospital have bacterial infection. Several modifications of the Park method were employed in an attempt to make the test more adaptable to a routine clinical laboratory, and the reliability of the present method was compared with that of the Park method. See histograms Methods One hundred and fifty-two tests were carried out on 141 subjects, of whom 24 were healthy adult controls; 51 were consecutive patients with untreated bacterial infections that were documented either 846 A.J.C.P. —Vol. 60 BITTNER ET AL. before or after the NBT test was done; 15 were consecutive patients with nonbacterial infectious processes: viral, mycotic, mycobacterial or parasitic; 51 were patients admitted to the University of Chicago Hospitals with noninfectious diseases, most of whom were acutely ill (Table 1). Acute bacterial infections were documented by positive cultures of blood, urine, sputum, spinal fluid or pus from patients with appropriate clinical pictures. In an attempt to adapt the NBT test to a routine clinical laboratory, the Park procedure 1 6 was modified as follows: 2 to 5 ml. of venous blood were collected in 8-ml. heparinized Vacutainer tubes (Becton-Dickinson). Within 40 minutes of venipuncture, 0.8 ml. of blood was pipetted into sterile polypropylene disposable tubes (Falcon), and to this was added 0.2 ml of 0.02% nitroblue tetrazolium dye (Sigma) in physiologic saline solution. The mixture was incubated at 37 C. for 30 minutes with continuous mixing on an oscillating device. Cover-slip smears were then made immediately, quickly air-dried, counterstained with Safranin O in 40% glycerin for 4 minutes, and mounted on glass slides with Permount (Fisher). All data are given as % cells showing dye reduction in 200 neutrophils counted under 400 X power; the criteria for the determination of the presence of reduced dye in cells were those of Matula and Paterson. 12 Except for the heparinized tubes, plastic tubes and pipettes were used throughout to avoid stimulation of the leukocytes by glass. Each sample was tested with simultaneous duplicates. All determinations of NBTffiPMN's were read blindly by a single observer. In forty-five subjects the NBT©PMN's were determined by both the Park method and the above procedure. T h e only alteration in the use of the Park method was to counterstain the cover-slip smears with Safranin O instead of Wright's stain. Four separate tests were done simultaneously in the subgroup, two with each method. Park method slides were coded and read with the slides from the larger series. Leukocyte count, differential, and sedimentation rate (Wintrobe method) were performed on the same day for 103 of the 152 test samples by regular technicians in the hospital general service laboratory. Results Figure 1 shows the results of the 152 tests in the four clinical categories. For the purposes of the between-population analyses, duplicate tests on single patients were deleted; the 141 original tests on 141 patients were analyzed. T h e healthy adult control population had a mean NBT©PMN count of 4.6%, with a standard error of 4.3%; patients with bacterial infection had a mean count of 11.3% (SE 13.4%); patients with nonbacterial infection had a mean count of 4.4% (SE 2.4%); patients with noninfectious illness had a mean count of 7.1% (SE 10.6%). Eight per cent N B T 0 P M N was arbitrarily selected as the boundary between normal and elevated because it resulted in the best concordance of NBT test results with clinical diagnosis, i.e., the least number of false positives plus false negatives. Fiftytwo per cent of tests on patients with bacterial infection were "abnormal," 28% of tests on patients with noninfectious illness were "abnormal," no test on any patient with non-bacterial infection was "abnormal," 14% of tests done on normal controls were "abnormal." As can be seen from Figure 1, there is a great deal of overlap in all four groups. T h e NBT test does not appear to be an effective discriminator between bacterial and other illnesses. There are, however, some average differences between groups which are statistically significant. In particular, the average NBTffiPMN count for the group with bacterial infections is significantly higher than the average counts for the population with non-bacterial infec- December 1973 847 UNSTIMULATED NBT TEST don and the normal controls (p < .05). It is not significantly different, however, from the average of the population With noninfectious illness (p < 0.07). (In view of the skewness of the distributions, a square-root transformation was employed with the hope that it would provide clearer discrimination between the groups. However, the results of the analysis of the transformed values were the same as those just stated). In 45 subjects the Park method was directly compared with our modification (see Fig. 2). The healthy adult control population had a mean NBTffiPMN count of 20.9% (SE 13.8%). Patients with bacterial infection had a mean value of 36.4% (SE 13.2%). Three patients with non-bacterial infection had a mean value of 17.8% (SE 9.8%). Patients with noninfectious illness had a mean value of 2 3 . 1 % (SE 13.8%). In comparing the reliability of the two methods, we arbitrarily chose 24% as the upper limit of normal for the Park method because that boundary resulted in the best possible correlation of NBT result with clinical diagnosis. Both methods conflicted with the underlying diagnosis in 24% of the 45 patients in whom the two methods were compared. As with the data derived using the modified method employed for the present study, the differences between population means were significant when patients with bacterial infection were compared with patients with non-bacterial infection (p < 0.005) and with controls (p < 0.01). Comparison of average test results in the patient populations with bacterial infection and noninfectious illness indicated significant differences for both test methods in this subgroup of 28 patients. The results after transformation by square-root analysis were again identical to the above. Graphs A, B, C, and D in Figure 3 compare the results of the first blindlyread test (abscissa) and the second (ordinate) for each sample done with the present 70 r 60 50 z f 40 © Im 30 20 I 10 :«:• „ B . °c,e.n<" l ln,ec,lon t* NonNonBocterml Infectious Infection Illness 54 .. Nor mtl , r. Con,rols n 52 X 11.3 4.4 7.1 4.6 SE 13.4 2.4 10.6 4.3 17 29 FIG. 1. NBT test results in 152 tests on 141 patients in 4 clinical categories. method, and Graphs E, F and G do likewise for samples done with the Park method. (The population of patients with non-bacterial infections in whom the Park method was done was not included in this analysis because of its small size). For the present method the standard deviation of the laboratory error as estimated from duplicate determinations in each of the 152 samples is 3.5, and each of the four clinical categories by itself has a comparable value. For the Park method the standard deviation of the laboratory error as estimated from duplicate determinations of the 42 samples is 8.8, and each of the 3 clinical categories analyzed was a comparable value. The laboratory error for both methods is thus fairly large compared with the differences between the mean N B T 0 P M N counts for each clinical A.J.C.P.—Vol. 60 BITTNER ET AL. 848 70 • 60 • : 50 • i z 1 40 - © • '• # I 30 Present method (#1) Park M e t h o d ! * 2 ) Compared in 4 5 patients in the 4 specified clinical categories The arbitrary c u t - o f f points ( 8 % forrfM and 2 4 % for # 2 ) are shown as dotted lines. • ## • • ' . 1 FIG. 2. Comparison of present method and Park method. 20 : 1 '• t 10 ! I • • : J •i Nc Bacter al „ „ „ . . „ . , „ , „ , „ . . . . . .. Hooter al Infect ous .Illness ..„,. Infection I. n„ f,e„c,t i o_n„ 1 1 2 2 : : .: . !: Normal ...iControls r 1 '2F© 3F© = I I Misdiagnoses IF© 5F© 5F0I OF© 3F© 3F© = 11 Misdiagnoses x 15.2 36.4 3.9 SE 16.3 Il3.2 1.6 17.8 7.2 23.1 9.8 10.4 13.8 5.2 20.9 5.4 13.8 category, and repeat tests would have given opposite results in 29% of the samples done with the present method and 12% of those done with the Park method if the respective arbitrary cut-off points of 8% and 24% had been employed. Graphs H, I and J in Figure 3 demonstrate the variability between the two test methods on the same subject. (The population of non-bacterial infection is again omitted because of its small size.) T h e line indicates the regression of the Park method on the present method in the 42 subjects in which the two methods were done simultaneously. It is clear that there is little agreement between the two test methods and that the extent of the disagreement is greater than can be accounted for by the laboratory error alone. In an attempt to determine the extent to which other readily available measures of inflammation might be combined with the NBT test to increase the ability of the test to predict bacterial infection, erythrocyte sedimentation rate (Wintrobe method), neutrophil count, and temperature were determined simultaneously in 103 subjects. ESR's ^ 50 mm/hr., absolute neutrophil counts ;> 9,000 cells/mm. 3 , and temperatures ^ 37.7 C. were arbitrarily designated "abnormal" (see Table 2). One of the 36 patients with noninfectious illness, a woman with polymyalgia rheumatica, had all four indices positive, and only 7 of 44 bacterially infected patients had all four acute-phase indices positive. Conversely, one patient with bacterial infection as a terminal complication of carcinomatosis had no index positive, while 36% of the patients with noninfectious December 1973 UNSTIMULATED NBT TEST illness had no index positive. Although the four indices are strikingly similar in that each is positive in approximately 60% of patients with bacterial infection and approximately 25% of patients with noninfectious illness, it can be seen that the NBT as a single test is not as reliable an indicator of bacterial infection as any of the other three taken alone. T h e best prediction obtainable was seen when any two of the indices were positive. We found that if one had available only the three more common acute-phase indices, that is, ESR, neutrophil count, and temperature, and if the criterion for strong suspicion of bacterial infection was that at least two of these must be positive, then 75% of patients with bacterial infection meet the criterion and 17% of patients with noninfectious illness have "false-positive" results. If, however, one had four indices available (ESR, neutrophil count, temperature, and NBT test) and the criterion for strong suspicion of bacterial infection was that at least two of these four must be positive, then 89% of patients with bacterial infection meet the criterion and 25% of patients with noninfectious illness have "false-positive" results. The patients with noninfectious illness who were positive according to this combination of indices had ulcerative colitis, fibrinous pericarditis, disseminated intravascular coagulation secondary to ruptured ectopic pregnancy, pancreatic carcinomatosis, polymyalgia rheumatica, psoriasis, and allergic granulomatous vasculitis. Discussion The main goals of this investigation were: (1) to adapt the unstimulated NBT test for use in a general hospital laboratory and to compare it with the original method of Park et al.; (2) to examine the inherent variability of this somewhat subjective procedure by performing simultaneous duplicate assays in a manner such that the source of the cells was unknown at the 849 time of the evaluation; (3) to extend observations of the NBT test in an adult patient population; (4) to compare the NBT test with other indices of inflammation. The Park method was modified to employ readily available materials and procedures for phlebotomy, and the number of steps involved was decreased. Our modified procedure and the Park method appear to be comparable in discriminating bacterial infection when done blindly, each method failing to correlate NBT test result with underlying diagnosis 24% of the time when the two methods were directly compared on the same 45 subjects. T h e laboratory error of the Park method, however, was substantially greater than that of the present method, although the disagreement between the two test methods was greater than the laboratory error could account for by itself. But since neither test reflects the true clinical state to an adequate degree, neither test can be incriminated as the one which upsets the between-test correlation. The results of this study stand in sharp contrast to the results of two earlier studies which found the NBT test to be a very satisfactory index of bacterial infection. 1216 However, our data are in substantial agreement with other studies. In a study of 356 pediatric patients, Feigin et al.6 found that 11% of patients with bacterial infection had false-negative tests and 20% of a controlled population known not to have bacterial infection had false positive tests. In a series of 296 pediatric patients, Humbert et al.10 noted that the test was falsely negative in 17% of patients with bacterial infection and positive in 4% of their controlled population. Attempts to employ the unstimulated NBT test in specific clinical situations, i.e., monitoring of intravenous catheter infections and infection in renal transplant patients, have yielded inconclusive results. Only two of 15 patients with intravenous catheter infection had 850 BITTNER ET AL. B. POPULATION OF NON-INFECTIOUS ILLNESS A. POPULATION OF BACTERIAL INFECTION 20 40 40 60 1st T E S T A.J.C.P. —Vol. 60 C. POPULATION OF NON-BACTERIAL INFECTION 0 20 40 0. CONTROL POPULATION 20 60 %NBT©PMN Grophs A,B,C and 0 demonstrating within-test correlation between simultaneous duplicates (present method 152 tests in 4 clinical categories). First slide read is on abscissa, second on ordinate. F. P O P U L A T I O N OF NON-INFECTIOUS ILLNESS E. POPULATION OF BACTERIAL INFECTION G. CONTROL POPULATION z 2 a. © 20 40 60 0 20 1st T E S T 40 60 %NBT©PMN Graphs E, F and G demonstrating within-test correlation of simultaneous duplicates (Park Method 4 2 tests in 3 clinical categories). First slide reod is on abscissa, second on ordinate. I. POPULATION H. POPULATION OF BACTERIAL INFECTION OF NON-INFECTIOUS ILLNESS J. CONTROL POPULATION 60 a o I £ a. 4 0 UJ © 2 l- c z CM B* 20 r = -0.42 20 40 60 0 20 1st METHOD 40 60 0 %NBT©PMN Graphs H, I, J demonstrating between-test correlation of two test methods ( 4 2 tests in 3 clinical categories) Present method on abscissa, Park Method on ordinate. Points represent the mean of the simultaneous duplicate N B T © P M N counts for the two methods on a given patient. FIG. 3. Within-test and between-test correlation: present method and Park method. December 1973 851 UNSTIMULATED NBT TEST Table 2. NBT Test Compared with Other Inflammatory Indices: Subgroup of 103 Subjects Pyoge nic Infections Total subjects All four positive None positive Erythrocyte sedimentation rate ^ 50 mm./hr. Polymorphonuclear leukocytes ^ 9,000 c/mm. 3 Temperature S 37.7 C. NBT -2. 8% Any two, NBT not available Any two, NBT available Any one index Noninfectious Illnesses Non-bacterial Infections Not mal Controls Total % Total % Total % Total % 44 7 1 36 1 13 0 54 10 0 8 — 3 36 13 0 7 — 16 2 29 66 9 25 3 23 0 0 24 34 25 33 39 43 55 77 57 75 89 98 7 9 11 6 9 21 19 25 31 17 25 58 1 6 0 4 4 6 8 46 0 31 31 46 0 0 2 0 0 2 0 0 20 0 0 20 0 80 Table 3. Accumulated Misdiagnoses by N B T Test False Negatives False Positives From the literature* Streptococcal cellulitis Chronic granulomatous disease Myeloperoxidase deficiency G-6-PD deficiency of neutrophils Congenital agammaglobulinemia Mixed cryoglobulinemia Lipochrome histiocytosis with rheumatoid arthritis Nephrotic syndrome with pneumococcal peritonitis and pneumococcal bacteremia Sickle-cell anemia with pneumococcal meningitis or salmonella osteomyelitis Local infection Histiocytosis X Shunt infection Alcoholism with abscesses Burn infection Pneumonia with influenza infection Ineffective antibiotic therapy Corticosteroid therapy (conflicting reports) Phenylbutazone therapy (in guinea pigs) Osteomyelitis in diabetes mellitus Uncomplicated urinary tract infection Malaria Candidosis Aseptic meningitis ECHO virus infection Herpes simplex and zoster infections Non-bacterial pneumonitis Acute rheumatic fever Active juvenile rheumatoid arthritis Neonates Congestive heart failure Chediak-Higashi syndrome Osteogenesis imperfecta Hemophilia Multiple drug overdosage Typhoid-paratyphoid vaccine Hodgkin's disease Oral contraceptive use Loaiasis Trichinosis Amebic hepatic abscess Normal controls From the present study Endometritis Infection in debilitated persons: Meningitis Pneumonia Abdominal abscess Carcinomatosis with septicemia Pseudomonas endocarditis Tertiary syphilis UTI and septicemia in patient with syringomyelia Ulcerative colitis Asthmatic attack Psoriasis Penicillin allergy Transfusion reaction Polymyalgia rheumatica Allergic granulomatous vasculitis Rheumatoid arthritis in an adult * False negatives, references 3, 4, 10, 12, 15, 20. False positives, references 1, 2, 5, 9, 10, 12, 14, 17, 19. 852 BITTNER ET AL. A.J.C.P. —Vol. 60 increases in their NBT counts associated values in the NBT test which were beyond with acute infection. 8 Five of seven renal- the range of normal without any evidence transplant patients subsequently proved for superimposed bacterial infection. Most to have bacterial infection and had demon- of these patients with falsely positive tests strable rises in % NBT-positive neutro- could be loosely classified as having been phils. 21 All seven, however, developed immunologically challenged. marked fever. Pyrexia was a more reliable We found the N B T test to be no more indicator of pyogenic infection in this concordant with bacterial infection than series. A possible explanation for the con- the other common indices of inflammation trasting findings concerning the test's (fever, neutrophilia, Wintrobe sedimentareliability is that the laboratory technics tion rate) and, in fact, it was less reliable employed by us (and in studies with com- than any one of the other three alone. parable results) were defective. On the When combined with the usual indices of other hand, all histochemical versions of bacterial infection, the N B T test increased the test involve subjective judgment, and the frequency with which bacterial infecwhen the diagnosis or clinical status of the tion was detected by 14%, but also inpatient is known, the possibility of in- creased the frequency with which patients advertent bias may lead to a much greater with non-bacterial infections would have agreement with the final diagnosis than been misdiagnosed by 8%. is inherent in the test itself. There is no We conclude, therefore, that the NBT indication that the more positive studies test may possibly be useful as an adjunct were done blindly. to other indices of infection, but that in In either case, a major objective of this a severely ill adult population it does not study was to test the hypothesis that the discriminate well between a population of NBT test would be useful in a general patients known to have bacterial infechospital in discriminating between severely tion and a population of patients who have ill patients with bacterial and non-bacterial other illnesses. illness. We find no evidence to support this hypothesis. References Our data confirm previous observations 1. Anderson B: NBT test in malaria. Lancet 2: of associated clinical situations in which 317, 1971 patients with bacterial infection have nor2. Chretien J H , Garagusi V: N B T test in parasitic mal NBT tests (Table 3). In our study, disease. Lancet 2:549, 1971 3. Cooper MR, Dechatelet LR, Lavia MF, et al: we found false-negative test results in Complete deficiency of leukocyte glucose-6severely debilitated patients. All six patients phosphate dehydrogenase with defective bacterial activity. J Clin Invest 49:21 a, 1970 with metastatic carcinoma and sepsis had negative results, as did five other patients 4. Douglas SD, Lahav M, Fudenberg H H : A reversible neutrophil bacterial defect associwho were terminally ill with sepsis folated with a mixed cryoglobulin. Am J Med 49:274-280, 1970 lowing cardiac surgery, myocardial infarc5. Farhadian H: T h e use of the N B T test in tion, major bowel surgery, or renal dialysis. rheumatic diseases of childhood. Chicago Society of Allergy, regular meeting, J u n e In addition, we confirmed previous studies 7, 1971, abstr which suggested that the NBT test may 6. Feigin RD, Schackelford PG, Choi SC: Prospecgive false positives in a number of clinical tive use of the nitroblue tetrazolium dye test in febrile disorders. J Pediatr 79:943situations (Table 3). Patients with active 947, 1971 ulcerative colitis, pyoderma gangrenosum, 7. Feigin RD, Schackelford PG, Choi SC, et al: psoriasis, rheumatoid arthritis, polyNitroblue tetrazolium dye test as an aid in the differential diagnosis of febrile disorders. myalgia rheumatica, fibrinous pericarditis, J Pediatr 78:230-237, 1971 or drug and transfusion reactions had 8. Freeman R, King B: Infective complications December 1973 9. 10. 11. 12. 13. 14. 15. 16. UNSTIMULATED NBT TEST of indwelling intravenous catheters and the monitoring of infections by the nitroblue tetrazolium test. Lancet 1:992-993, 1972 Crush OC, Mauer AM: Neutrophil function and NBT dye reduction. Lancet 2:383, 1969 Humbert JR, Marks MI, Hathaway WE, et al: Nitroblue tetrazolium in acute infections. Pediatrics 48:259-267, 1971 Nitroblue tetrazolium: A routine test? (editorial). Lancet 2:909, 1971 Matula G, Paterson PY: Spontaneous in vitro reduction of nitroblue tetrazolium by neutrophils of adult patients with bacterial infections. N EnglJ Med 285:311-316, 1971 Miller DR, Kaplan HG: Decreased nitroblue tetrazolium dye reduction in the phagocytes of patients receiving prednisone. Pediatrics 45:861-865, 1970 Norden C, Reese R: Oral contraceptives and NBT test. N EnglJ Med 287:254, 1972 Park BH: The use and limitations of the nitroblue tetrazolium test as a diagnostic aid. J Pediatr 78:376-378, 1971 Park BH, Fikrig SM, Smithwick EM: Infection 853 and nitroblue-tetrazolium reduction by neutrophils: A diagnostic aid. Lancet 2:532-534, 1968 17. Park BH, Holmes BM, Rodey GE, et al: Nitroblue tetrazolium test in children with fatal chronic granulomatous disease and newborn infants. Lancet 1:157, 1969 18. Park BH, South MA, Barret FF, et al: The use of the nitroblue tetrazolium reduction (NBT) test in diagnosis and treatment of bacterial endocarditis. Pediatr Res 4:463, 1970 (abstr) 19. Soonattrakul W, Andersen B: Nitroblue tetrazolium test in lymphomas. N Engl J Med 288:218, 1973 20. Strauss RR, Paul BB, Sbarra AJ: Effect of phenylbutazone on phagocytosis and intracellular killing of guinea pig polymorphonuclear leukocytes. J Bacteriol 96:1982-1990, 1968 21. Wollman MR, David DS, Brennan BL, et al: T h e nitroblue-tetrazolium test. Lancet 2:289291, 1972