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Why bother with the clinical virology laboratory?
i
Editorial Henry H. Balfour, Jr., M.D. Associate Professor Laboratory Medicine & Pathology, and Pediatrics Director, Division of Clinical Microbiology University of Minnesota Health Sciences Center 420 Delaware Street S.E. Minneapolis, Minnesota 55455 Why Bother with the Clinical Virology L a b o r a t o r y ? Viruses often are far down on the list of suspected pathogens. Viral studies are important, however, not only for epidemiologic purposes but also for patient management. Appropriate use of the viral diagnostic laboratory requires knowledge of which patients to study, what specimens to collect, and how to interpret the results. Probably the biggest negative factor in use of the virus laboratory has been the time delay from collection of specimen to receipt of results. This time can be shortened considerably by determining antibody titers in single serum specimens and by telephoning the physician as soon as a viral isolate is suspected. Although at present there are few effective antiviral agents, within the next few years more prophylactic and therapeutic antiviral compounds will be available. Now is the time to sharpen our diagnostic acumen so that we can appropriately prescribe antiviral compounds! It is my opinion that patients, who have the types of infections listed in the left-hand column of Table 1 should have viral diagnostic tests. Why study infants with congenital or neonatal infections? An early diagnosis of viral infection en-
ables the clinician to give parents a reasonably accurate prognosis. Early isolation of herpes simplex virus makes it possible to treat with adenine arabinoside which may be beneficial. It is important to know whether an infant has congenital rubella because that child may shed virus for several years after birth and is a risk to rubella-susceptible pregnant women. Since respiratory infections are the most common form of acute viral illness in children and adults, it would be a mammoth task to collect viral specimens from all these patients. It is, however, valuable to have specimens from several patients at the beginning of an epidemic. Knowledge of which virus is causing the epidemic helps the clinician to predict incubation periods, spread in families, and complications. For example, if respiratory syncytial virus is present in a community, pediatricians know that bronchiolitis and pneumonia will occur in young children. On the other hand, the presence of influenza A virus indicates that children are likely to have relatively mild upper-respiratory symptoms while adults will be sicker and may develop pneumonia. If influenza A virus is known to be present, one may want to prescribe amantidine hydrochloride for prophylaxis of contacts. Viral studies are of great value in central nervous system (CNS) infections. For example, California (La Crosse) encephalitis is one of the most common forms of acute summertime CNS infections in children. A diagnosis of California encephalitis can be nearly assured if a patient has precipitating anti-
Table I Which Patients Should Have Viral Studies and What Specimens to Collect Cate~,orv oJh~ection
Newborn (congenital or acquired in the neonatal period) Respiratory (index case or lower respiratory tract involvement) Central nervous system Hepatitis Rashes Infections in immunodeficient patients * If available.
Specimens Recommemlcdfor Diagm~sis
Throat swab. urine, cerebrospinal fluid*, stool, vesicular fluid*, serum Throat swab. serum Throat swab, stool, urine, cerebrospinal fluid, biopsy material*, serum Serum Throat sv,'ab, stool, vesicular fluid*, serum Urine, throat, heparinized blood, bronchial washings*, serum
body to La Crosse virus in a serum specimen. Since focal neurologic findings may occur in California encephalitis as well as in herpes virus encephalitis, a diagnosis of California encephalitis may spare the patient unnecessary and even invasive diagnostic procedures. Furthermore, adenine arabinoside, which has been shown to have some efficacy in herpes virus encephalitis, is of no value in California encephalitis. Viral studies are needed in patients with hepatitis because individuals whose sera contain hepatitis B surface antigen may be a risk to members of their households, other ]aatients, and medical personnel. Rashes, especially that associated with rubella, are often difficult to recognize. The diagnosis of rubella is important to make in pregnant women when there has been potential exposure to the disease. Because exanthems that resemble rubella are produced by adenoand enteroviruses, the laboratory is frequently needed to rule out a true rubella exposure in a pregnant patient. The most important group of patients to study for the presence of viruses are those with primary or acquired immunodeficiency. Viral infections in such patients are most frequently caused by one of the herpes virus group, usually cytomegalovirus. These infections are characterized by fever and leukopenia. If laboratory confirmation of viral infection is obtained, the patient's immunosuppressive regimen is generally decreased to permit his immunologic system to combat the viral pathogen. I do not believe that viruses are normal flora. Therefore, isolation of a virus from a patient, particularly an adult, essentially is diagnostic of acute infection with that agent. If viral cultures are not negative or are not done, serum antibody tests may be needed for diagnosis. Traditionally, paired sera are requested, and a definite diagnosis must wait many weeks. The patient may be entirely well four to eight weeks after onset of illness and may not want the hassle of returning to the doctor's office to have a convalescent sample drawn. Because of this, 1 stress that analysis of a single serum specimen can be of great value. High liters (such as an adenovirus CF tiler of
128 or a mumps titer of 64) suggest recent infection. Likewise, the absence of antibody one week to ten days after the onset of illness rules out infection with that agent. Single serum specimens are of great value in determining immune status. This is becoming increasingly important as we realize that serologic conversion failures have occurred with both measles and rubella vaccines. Lastly, it is essential to determine varicella immune status in immunodeficient children because chickenpox can be life threatening in these patients. An immunocompromised child lacking antibodies to varicella should receive zoster immune globulin or plasma when exposed to chickenpox. I urge sending specimens to the clinical virology laboratory. Even though we virologists constantly talk about things we can't see, the services we provide are not far-fetched but really basic to appropriate modem day management of infectious diseases.
Workshops and Meetings Infectious Disease Symposium (16th). Wilmington, Delaware. May 1-4. Contact: William J. Holloway, Infectious Disease Research Laboratory Delaware Division, Wilmington Medical Center, Wilmington, Delaware 19899. Methods of Immunologic Research and Diagnosis. Buffalo, New York. June 4-22. Sponsored by the Center for Immunology of the State University of New York at Buffalo. Contact: James F. Mohn, M.D., Director, The Center for Immunology, State University of New York at Buffalo, 210 Sherman Hall, Buffalo, New York 14214 Workshop on Clinical Protozoology. Philadelphia, Pennsylvania. June 26-29. Sponsored by the Eastern Pennsylvania ASM Branch.
Contact: J. A. Faricelli, Wm. Pepper Laboratory, Hospital of the University of Pennsylvania, 24th and Spruce St., Philadelphia, Pennsylvania 19104. American Society of Parasitologists. Minneapolis, Minnesota. July 29August 3. Contact: Clayton R. Page, Department of Biology, Tulane University, New Orleans, Louisiana 70118. International Conference of Atypical Mycobacteria. Denver, Colorado. September 5-8. Contact: P. T. Davidson, National Jewish Hospital and Research Center, 3800 Colfax Avenue, Denver, Colorado 80206.
References 1. Balfour, H. H. Jr., R. J. Majerle, and C. K. Edelman. 1973. California arbovirus (La Crosse) infections. II. Precipitin antibody tests for the diagnosis of California encephalitis. Infect. Immun. 8:947-951. 2. Balfour, H. H. Jr., and B. A. Burke. 1975. Viral and mycoplasmal pneumonias: Reviewing current concepts. Postgrad. Med. 58(7):48-54. 3. Balfour, H. H. Jr., M. S. Slade, J. M. Kalis, R. J. Howard, R. L. Simmons, and J. S. Najarian. 1977. Viral infections in renal transplant donors and their recipients: A prospective study. Surgery 81:487-492. 4. Balfour, H. H. Jr., and D. P. Amren. 1978. Rubella, measles and mumps antibodies following vaccination of children by one suburban medical center: a potential rubella problem. Am. J. Dis. Child. 132:573-577. 5. Hall, C. B., R. G. Douglas, J. M. Geiman, and M. K. Messner. 1975. Nosocomial respiratory syncytial virus infections. New Engl. J. Med. 293:13431346. 6. Hall, C. B., and R. G. Douglas. 1976. Respiratory syncytial virus and influenza: Practical community surveillance. Am. J. Dis. Child. 130:615-620. 7. Hansbaw, J. B. 1971. Congenital cytomegalovirus infection: A fifteen year perspective. J. Infect. Dis. 123:555-561. 8. D. Pavan-Langston, R. A/Buchanan, and C. A. Alford, Jr., editors. 1975. Adenine arabinoside: An antiviral agent. Raven Press, New York.
Letters to the Editor ii
To the Editor: Follow-up on problems with autoclavable bags: A preliminary report on sterilization problems with autoclavable bags appeared in a recent issue (Clin. MicrobioI. Newsl. 1:2, I979). Through trial and error we have found that the best method for achieving sterilization of discarded plated material is to stack the Petri dishes in neat columns in the autoclavable bag and to fill the bag not more than two-thirds full. (It is impor-
Editors:
i
tant to avoid air pockets between dishes.) The top of the bag should be left open. A minimum of one inch of water is added, and the bag is then autoclaved for40 minutes at 126°C. With this procedure, Bacillus steareothermophihts spores (Attest) are killed. The biological indicator can be retrieved by tying it with string in such a way that it hangs near the inside surface of the bag about half way down. Mrs. Marjorie Dole Microbiologist Pennsylvania Hospital Philadelphia, Pennsylvania
Donna J. Blazevic, L. R. McCarthy, and Josephine A. Morello
Subscription Rates in U.S. and Canada: one year $42.50; two years $80.00; three years $110.00. All other countries: one year $57.50; two years $109.50; three years $153.25. Single copies are $2.00 in U.S. and Canada, $2.65 all other countries. Single issues are available in quantity (prices available upon request). All subscriptions are payable in advance. Foreign subscriptions are sent guaranteed air mail. First class postage paid in U.S. and Canada. Address correspondence regarding subscription to: Clinical MicrobiologyNewsletter. G. K. Hall & Co., 70 Lincoln St., Boston, Massachusetts 02111. Please include zip code in subscription address. The ClinicalMicrobiology Newsletter is published twice monthly. All fights, including that of translation into other languages, reserved. Photomechanical reproduction (photocopy, microcopy) of this newsletter or parts thereof without special permission of the publisher is prohibited.
Editorial Henry H. Balfour, Jr., M.D. Associate Professor Laboratory Medicine & Pathology, and Pediatrics Director, Division of Clinical Microbiology University of Minnesota Health Sciences Center 420 Delaware Street S.E. Minneapolis, Minnesota 55455 Why Bother with the Clinical Virology L a b o r a t o r y ? Viruses often are far down on the list of suspected pathogens. Viral studies are important, however, not only for epidemiologic purposes but also for patient management. Appropriate use of the viral diagnostic laboratory requires knowledge of which patients to study, what specimens to collect, and how to interpret the results. Probably the biggest negative factor in use of the virus laboratory has been the time delay from collection of specimen to receipt of results. This time can be shortened considerably by determining antibody titers in single serum specimens and by telephoning the physician as soon as a viral isolate is suspected. Although at present there are few effective antiviral agents, within the next few years more prophylactic and therapeutic antiviral compounds will be available. Now is the time to sharpen our diagnostic acumen so that we can appropriately prescribe antiviral compounds! It is my opinion that patients, who have the types of infections listed in the left-hand column of Table 1 should have viral diagnostic tests. Why study infants with congenital or neonatal infections? An early diagnosis of viral infection en-
ables the clinician to give parents a reasonably accurate prognosis. Early isolation of herpes simplex virus makes it possible to treat with adenine arabinoside which may be beneficial. It is important to know whether an infant has congenital rubella because that child may shed virus for several years after birth and is a risk to rubella-susceptible pregnant women. Since respiratory infections are the most common form of acute viral illness in children and adults, it would be a mammoth task to collect viral specimens from all these patients. It is, however, valuable to have specimens from several patients at the beginning of an epidemic. Knowledge of which virus is causing the epidemic helps the clinician to predict incubation periods, spread in families, and complications. For example, if respiratory syncytial virus is present in a community, pediatricians know that bronchiolitis and pneumonia will occur in young children. On the other hand, the presence of influenza A virus indicates that children are likely to have relatively mild upper-respiratory symptoms while adults will be sicker and may develop pneumonia. If influenza A virus is known to be present, one may want to prescribe amantidine hydrochloride for prophylaxis of contacts. Viral studies are of great value in central nervous system (CNS) infections. For example, California (La Crosse) encephalitis is one of the most common forms of acute summertime CNS infections in children. A diagnosis of California encephalitis can be nearly assured if a patient has precipitating anti-
Table I Which Patients Should Have Viral Studies and What Specimens to Collect Cate~,orv oJh~ection
Newborn (congenital or acquired in the neonatal period) Respiratory (index case or lower respiratory tract involvement) Central nervous system Hepatitis Rashes Infections in immunodeficient patients * If available.
Specimens Recommemlcdfor Diagm~sis
Throat swab. urine, cerebrospinal fluid*, stool, vesicular fluid*, serum Throat swab. serum Throat swab, stool, urine, cerebrospinal fluid, biopsy material*, serum Serum Throat sv,'ab, stool, vesicular fluid*, serum Urine, throat, heparinized blood, bronchial washings*, serum
body to La Crosse virus in a serum specimen. Since focal neurologic findings may occur in California encephalitis as well as in herpes virus encephalitis, a diagnosis of California encephalitis may spare the patient unnecessary and even invasive diagnostic procedures. Furthermore, adenine arabinoside, which has been shown to have some efficacy in herpes virus encephalitis, is of no value in California encephalitis. Viral studies are needed in patients with hepatitis because individuals whose sera contain hepatitis B surface antigen may be a risk to members of their households, other ]aatients, and medical personnel. Rashes, especially that associated with rubella, are often difficult to recognize. The diagnosis of rubella is important to make in pregnant women when there has been potential exposure to the disease. Because exanthems that resemble rubella are produced by adenoand enteroviruses, the laboratory is frequently needed to rule out a true rubella exposure in a pregnant patient. The most important group of patients to study for the presence of viruses are those with primary or acquired immunodeficiency. Viral infections in such patients are most frequently caused by one of the herpes virus group, usually cytomegalovirus. These infections are characterized by fever and leukopenia. If laboratory confirmation of viral infection is obtained, the patient's immunosuppressive regimen is generally decreased to permit his immunologic system to combat the viral pathogen. I do not believe that viruses are normal flora. Therefore, isolation of a virus from a patient, particularly an adult, essentially is diagnostic of acute infection with that agent. If viral cultures are not negative or are not done, serum antibody tests may be needed for diagnosis. Traditionally, paired sera are requested, and a definite diagnosis must wait many weeks. The patient may be entirely well four to eight weeks after onset of illness and may not want the hassle of returning to the doctor's office to have a convalescent sample drawn. Because of this, 1 stress that analysis of a single serum specimen can be of great value. High liters (such as an adenovirus CF tiler of
128 or a mumps titer of 64) suggest recent infection. Likewise, the absence of antibody one week to ten days after the onset of illness rules out infection with that agent. Single serum specimens are of great value in determining immune status. This is becoming increasingly important as we realize that serologic conversion failures have occurred with both measles and rubella vaccines. Lastly, it is essential to determine varicella immune status in immunodeficient children because chickenpox can be life threatening in these patients. An immunocompromised child lacking antibodies to varicella should receive zoster immune globulin or plasma when exposed to chickenpox. I urge sending specimens to the clinical virology laboratory. Even though we virologists constantly talk about things we can't see, the services we provide are not far-fetched but really basic to appropriate modem day management of infectious diseases.
Workshops and Meetings Infectious Disease Symposium (16th). Wilmington, Delaware. May 1-4. Contact: William J. Holloway, Infectious Disease Research Laboratory Delaware Division, Wilmington Medical Center, Wilmington, Delaware 19899. Methods of Immunologic Research and Diagnosis. Buffalo, New York. June 4-22. Sponsored by the Center for Immunology of the State University of New York at Buffalo. Contact: James F. Mohn, M.D., Director, The Center for Immunology, State University of New York at Buffalo, 210 Sherman Hall, Buffalo, New York 14214 Workshop on Clinical Protozoology. Philadelphia, Pennsylvania. June 26-29. Sponsored by the Eastern Pennsylvania ASM Branch.
Contact: J. A. Faricelli, Wm. Pepper Laboratory, Hospital of the University of Pennsylvania, 24th and Spruce St., Philadelphia, Pennsylvania 19104. American Society of Parasitologists. Minneapolis, Minnesota. July 29August 3. Contact: Clayton R. Page, Department of Biology, Tulane University, New Orleans, Louisiana 70118. International Conference of Atypical Mycobacteria. Denver, Colorado. September 5-8. Contact: P. T. Davidson, National Jewish Hospital and Research Center, 3800 Colfax Avenue, Denver, Colorado 80206.
References 1. Balfour, H. H. Jr., R. J. Majerle, and C. K. Edelman. 1973. California arbovirus (La Crosse) infections. II. Precipitin antibody tests for the diagnosis of California encephalitis. Infect. Immun. 8:947-951. 2. Balfour, H. H. Jr., and B. A. Burke. 1975. Viral and mycoplasmal pneumonias: Reviewing current concepts. Postgrad. Med. 58(7):48-54. 3. Balfour, H. H. Jr., M. S. Slade, J. M. Kalis, R. J. Howard, R. L. Simmons, and J. S. Najarian. 1977. Viral infections in renal transplant donors and their recipients: A prospective study. Surgery 81:487-492. 4. Balfour, H. H. Jr., and D. P. Amren. 1978. Rubella, measles and mumps antibodies following vaccination of children by one suburban medical center: a potential rubella problem. Am. J. Dis. Child. 132:573-577. 5. Hall, C. B., R. G. Douglas, J. M. Geiman, and M. K. Messner. 1975. Nosocomial respiratory syncytial virus infections. New Engl. J. Med. 293:13431346. 6. Hall, C. B., and R. G. Douglas. 1976. Respiratory syncytial virus and influenza: Practical community surveillance. Am. J. Dis. Child. 130:615-620. 7. Hansbaw, J. B. 1971. Congenital cytomegalovirus infection: A fifteen year perspective. J. Infect. Dis. 123:555-561. 8. D. Pavan-Langston, R. A/Buchanan, and C. A. Alford, Jr., editors. 1975. Adenine arabinoside: An antiviral agent. Raven Press, New York.
Letters to the Editor ii
To the Editor: Follow-up on problems with autoclavable bags: A preliminary report on sterilization problems with autoclavable bags appeared in a recent issue (Clin. MicrobioI. Newsl. 1:2, I979). Through trial and error we have found that the best method for achieving sterilization of discarded plated material is to stack the Petri dishes in neat columns in the autoclavable bag and to fill the bag not more than two-thirds full. (It is impor-
Editors:
i
tant to avoid air pockets between dishes.) The top of the bag should be left open. A minimum of one inch of water is added, and the bag is then autoclaved for40 minutes at 126°C. With this procedure, Bacillus steareothermophihts spores (Attest) are killed. The biological indicator can be retrieved by tying it with string in such a way that it hangs near the inside surface of the bag about half way down. Mrs. Marjorie Dole Microbiologist Pennsylvania Hospital Philadelphia, Pennsylvania
Donna J. Blazevic, L. R. McCarthy, and Josephine A. Morello
Subscription Rates in U.S. and Canada: one year $42.50; two years $80.00; three years $110.00. All other countries: one year $57.50; two years $109.50; three years $153.25. Single copies are $2.00 in U.S. and Canada, $2.65 all other countries. Single issues are available in quantity (prices available upon request). All subscriptions are payable in advance. Foreign subscriptions are sent guaranteed air mail. First class postage paid in U.S. and Canada. Address correspondence regarding subscription to: Clinical MicrobiologyNewsletter. G. K. Hall & Co., 70 Lincoln St., Boston, Massachusetts 02111. Please include zip code in subscription address. The ClinicalMicrobiology Newsletter is published twice monthly. All fights, including that of translation into other languages, reserved. Photomechanical reproduction (photocopy, microcopy) of this newsletter or parts thereof without special permission of the publisher is prohibited.