Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome

Page  1 Reprinted by the US. DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE CENTERS FOR DISEASE CONTROL from MMWR SUPPLEMENT, August 14, 1987, Vol. 36, No. 1S, pp. 3S-15S CENTERS FOR DISEASE CONTROL August 14, 1987 /Vol. 36 /No. 1S Supplement MORBIDITY AND MORTALITY WEEKLY REPORT Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome AIDS Program Center for Infectious Diseases Centers for Disease Control Atlanta, Georgia 30333 11111IIIIJ I IIIi IIIil 5571095.0284041

Page  2 Supplements to the MMWR are published by the Epidemiology Program Office, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333. SUGGESTED CITATION Centers for Disease Control. Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome. MMWR 1987;36(suppi no. 1S):[inclusive page numbers]. Centers for Disease Control....................James 0. Mason, M.D., Dr.P.H. Director Center for Infectious Diseases.............Frederick A. Murphy, D.V.M., Ph.D. Acting Director AIDS Program............................................................... Jam es W. Curran, M.D. Director This report was prepared bv: Epidemiology Program Office................................................ Carl W. Tyler, Jr., M.D. Director Michael B. Gregg, M.D. Editor, MMWR Editorial Services............................................................... R. Elliott Churchill, M.A. Chief Ruth Greenberg Editorial Assistant Use of trade names is for identification only and does not constitute endorsement by the Public Health. Service or the U.S. Department of Health and Human Services.

Page  3 Vol. 36 /No. 1S MMWR 3SS Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome Reported by Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases, CDC INTRODUCTION The following revised case definition for surveillance of acquired immunodeficiency syndrome (AIDS) was developed by CDC in collaboration with public health and clinical specialists. The Council of State and Territorial Epidemiologists (CSTE) has officially recommended adoption of the revised definition for national reporting of AIDS. The objectives of the revision are a) to track more effectively the severe disabling morbidity associated with infection with human immunodeficiency virus (HIV) (including HIV-1 and HIV-2); b) to simplify reporting of AIDS cases; c) to increase the sensitivity and specificity of the definition through greater diagnostic application of laboratory evidence for HIV infection; and d) to be consistent with current diagnostic practice, which in some cases includes presumptive, i.e., without confirmatory laboratory evidence, diagnosis of AIDS-indicative diseases (e.g., Pneumocystis carinii pneumonia, Kaposi's sarcoma). The definition is organized into three sections that depend on the status of laboratory evidence of HIV infection (e.g., HIV antibody) (Figure 1). The major proposed changes apply to patients with laboratory evidence for HIV infection: a) inclusion of HIV encephalopathy, HIV wasting syndrome, and a broader range of specific AIDS-indicative diseases (Section II.A); b) inclusion of AIDS patients whose indicator diseases are diagnosed presumptively (Section II.B); and c) elimination of exclusions due to other causes of immunodeficiency (Section L.A). Application of the definition for children differs from that for adults in two ways. First, multiple or recurrent serious bacterial infections and lymphoid interstitial pneumonia/pulmonary lymphoid hyperplasia are accepted as indicative of AIDS among children but not among adults. Second, for children<1 5 months of age whose mothers are thought to have had HIV infection during the child's perinatal period, the laboratory criteria for HIV infection are more stringent, since the presence of HIV antibody in the child is, by itself, insufficient evidence for HIV infection because of the persistence of passively acquired maternal antibodies < 15 months after birth. The new definition is effective immediately. State and local health departments are requested to apply the new definition henceforth to patients reported to them. The initiation of the actual reporting of cases that meet the new definition is targeted for September 1, 1987, when modified computer software and report forms should be in place to accommodate the changes. CSTE has recommended retrospective applichtion of the revised definition to patients already reported to health departments. The new definition follows:

Page  4 4S MMWR August 14, 1987 1987 REVISION OF CASE DEFINITION FOR AIDS FOR SURVEILLANCE PURPOSES For national reporting, a case of AIDS is defined as an illness characterized by one or more of the following "indicator" diseases, depending on the status of laboratory evidence of HIV infection, as shown below. I. Without Laboratory Evidence Regarding HIV Infection If laboratory tests for HIV were not performed or gave inconclusive results (See Appendix 1) and the patient had no other cause of immunodeficiency listed in Section L.A below, then any disease listed in Section L.B indicates AIDS if it was diagnosed by a definitive method (See Appendix Il). A. Causes of immunodeficiency that disqualify diseases as indicators of AIDS in the absence of laboratory evidence for HIV infection 1. high-dose or long-term systemic corticosteroid therapy or other immunosuppressive/cytotoxic therapy -3 months before the onset of the indicator disease 2. any of the following diseases diagnosed <3 months after diagnosis of the indicator disease: Hodgkin's disease, non-Hodgkin's lymphoma (other than primary brain lymphoma), lymphocytic leukemia, multiple myeloma, any other cancer of lymphoreticular or histiocytic tissue, or angioimmunoblastic lymphadenopathy 3. a genetic (congenital) immunodeficiency syndrome or an acquired immunodeficiency syndrome atypical of HIV infection, such as one involving hypogammaglobulinemia B. Indicator diseases diagnosed definitively (See Appendix II) 1. candidiasis of the esophagus, trachea, bronchi, or lungs 2. cryptococcosis, extrapulmonary 3. cryptosporidiosis with diarrhea persisting >1 month 4. cytomegalovirus disease of an organ other than liver, spleen, or lymph nodes in a patient >1 month of age 5. herpes simplex virus infection causing a mucocutaneous ulcer that persists longer than 1 month; or bronchitis, pneumonitis, or esophagitis for any duration affecting a patient >1 month of age 6. Kaposi's sarcoma affecting a patient < 60 years of age 7. lymphoma of the brain (primary) affecting a patient < 60 years of age 8. lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia (LIP/PLH complex) affecting a child <13 years of age 9. Mycobacterium avium complex or M. kansasii disease, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar lymph nodes) 10. Pneumocystis carinii pneumonia 11. progressive multifocal leukoencephalopathy 12. toxoplasmosis of the brain affecting a patient >1 month of age II. With Laboratory Evidence for HIV Infection Regardless of the presence of other causes of immunodeficiency (LA), in the presence of laboratory evidence for HIV infection (See Appendix 1), any disease listed above (1.6) or below (II.A or 11.B) indicates a diagnosis of AIDS.

Page  5 Vol. 36 / No. 1S MMWR 5S A. Indicator diseases diagnosed definitively (See Appendix II) 1. bacterial infections, multiple or recurrent (any combination of at least two within a 2-year period), of the following types affecting a child < 13 years of age: septicemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media or superficial skin or mucosal abscesses), caused by Haemophilus, Streptococcus (including pneumococcus), or other pyogenic bacteria 2. coccidioidomycosis, disseminated (at a site other than or in addition to lungs or cervical or hilar lymph nodes) 3. HIV encephalopathy (also called "HIV dementia," "AIDS dementia," or "subacute encephalitis due to HIV") (See Appendix II for description) 4. histoplasmosis, disseminated (at a site other than or in addition to lungs or cervical or hilar lymph nodes) 5. isosporiasis with diarrhea persisting >1 month 6. Kaposi's sarcoma at any age 7. lymphoma of the brain (primary) at any age 8. other non-Hodgkin's lymphoma of B-cell or unknown immunologic phenotype and the following histologic types: a. small noncleaved lymphoma (either Burkitt or non-Burkitt type) (See Appendix IV for equivalent terms and numeric codes used in the International Classification of Diseases, Ninth Revision, Clinical Modification) b. immunoblastic sarcoma (equivalent to any of the following, although not necessarily all in combination: immunoblastic lymphoma, largecell lymphoma, diffuse histiocytic lymphoma, diffuse undifferentiated lymphoma, or high-grade lymphoma) (See Appendix IV for equivalent terms and numeric codes used in the International Classification of Diseases, Ninth Revision, Clinical Modification) Note: Lymphomas are not included here if they are of T-cell immunologic phenotype or their histologic type is not described or is described as "Iymphocytic," "lymphoblastic," "small cleaved," or "plasmacytoid lymphocytic" 9. any mycobacterial disease caused by mycobacteria other than M. tuberculosis, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar lymph nodes) 10. disease caused by M. tuberculosis, extrapulmonary (involving at least one site outside the lungs, regardless of whether there is concurrent pulmonary involvement) 11. Salmonella (nontyphoid) septicemia, recurrent 12. HIV wasting syndrome (emaciation, "slim disease") (See Appendix II for description) B. Indicator diseases diagnosed presumptively (by a method other than those in Appendix II) Note: Given the seriousness of diseases indicative of AIDS, it is generally important to diagnose them definitively, especially when therapy that would be used may have serious side effects or when definitive diagnosis is needed

Page  6 esS MMWR August 14, 1987 for eligibility for antiretroviral therapy. Nonetheless, in some situations, a patient's condition will not permit the performance of definitive tests. In other situations, accepted clinical practice may be to diagnose presumptively based on the presence of characteristic clinical and laboratory abnormalities. Guidelines for presumptive diagnoses are suggested in Appendix Ill. 1. candidiasis of the esophagus 2. cytomegalovirus retinitis with loss of vision 3. Kaposi's sarcoma 4. lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia (LIP/PLH complex) affecting a child <13 years of age 5. mycobacterial disease (acid-fast bacilli with species not identified by culture), disseminated (involving at least one site other than or in addition to lungs, skin, or cervical or hilar lymph nodes) 6. Pneumocystis carinii pneumonia 7. toxoplasmosis of the brain affecting a patient >1 month of age Ill. With Laboratory Evidence Against HIV Infection With laboratory test results negative for HIV infection (See Appendix 1), a diagnosis of AIDS for surveillance purposes is ruled out unless: A. all the other causes of immunodeficiency listed above in Section LA are excluded; AND B. the patient has had either: 1. Pneumocystis carinii pneumonia diagnosed by a definitive method (See Appendix II); OR 2. a. any of the other diseases indicative of AIDS listed above in Section 1.B diagnosed by a definitive method (See Appendix II); AND b. a T-helper/inducer (CD4) lymphocyte count <400/mm3. COMMENTARY The surveillance of severe disease associated with HIV infection remains an essential, though not the only, indicator of the course of the HIV epidemic. The number of AIDS cases and the relative distribution of cases by demographic, geographic, and behavioral risk variables are the oldest indices of the epidemic, which began in 1981 and for which data are available retrospectively back to 1978. The original surveillance case definition, based on then-available knowledge, provided useful epidemiologic data on severe HIV disease (1 ). To ensure a reasonable predictive value for underlying immunodeficiency caused by what was then an unknown agent, the indicators of AIDS in the old case definition were restricted to particular opportunistic diseases diagnosed by reliable methods in patients without specific known causes of immunodeficiency. After HIV was discovered to be the cause of AIDS, however, and highly sensitive and specific HIV-antibody tests became available, the spectrum of manifestations of HIV infection became better defined, and classification systems for HIV infection were developed (2-5). It became apparent that some progressive, seriously disabling, and even fatal conditions (e.g., encephalopathy, wasting syndrome) affecting a substantial number of HIV-infected patients were not subject to epidemiologic surveillance, as they were not included in the AIDS

Page  7 Vol. 36/ No. IS MMWR 7S case definition. For reporting purposes, the revision adds to the definition most of those severe non-infectious, non-cancerous HIV-associated conditions that are categorized in the CDC clinical classification systems for HIV infection among adults and children (4,5). Another limitation of the old definition was that AIDS-indicative diseases are diagnosed presumptively (i.e., without confirmation by methods required by the old definition) in 10%-15% of patients diagnosed with such diseases; thus, an appreciable proportion of AIDS cases were missed for reporting purposes (6,7). This proportion may be increasing, which would compromise the old case definition's usefulness as a tool for monitoring trends. The revised case definition permits the reporting of these clinically diagnosed cases as long as there is laboratory evidence of HIV infection. The effectiveness of the revision will depend on how extensively HIV-antibody tests are used. Approximately one third of AIDS patients in the United States have been from New York City and San Francisco, where, since 1985, < 7% have been reported with HIV-antibody test results, compared with > 60% in other areas. The impact of the revision on the reported numbers of AIDS cases will also depend on the proportion of AIDS patients in whom indicator diseases are diagnosed presumptively rather than definitively. The use of presumptive diagnostic criteria varies geographically, being more common in certain rural areas and in urban areas with many indigent AIDS patients. To avoid confusion about what should be reported to health departments, the term "AIDS' should refer only to conditions meeting the surveillance definition. This definition is intended only to provide consistent statistical data for public health purposes. Clinicians will not rely on this definition alone to diagnose serious disease caused by HIV infection in individual patients because there may be additional information that would lead to a more accurate diagnosis. For example, patients who are not reportable under the definition because they have either a negative HIVantibody test or, in the presence of HIV antibody, an opportunistic disease not listed in the definition as an indicator of AIDS nonetheless may be diagnosed as having serious HIV disease on consideration of other clinical or laboratory characteristics of HIV infection or a history of exposure to HIV. Conversely, the AIDS surveillance definition may rarely misclassify other patients as having serious HIV disease if they have no HIV-antibody test but have an AIDS-indicative disease with a background incidence unrelated to HIV infection, such as cryptococcal meningitis. The diagnostic criteria accepted by the AIDS surveillance case definition should not be interpreted as the standard of good medical practice. Presumptive diagnoses are accepted in the definition because not to count them would be to ignore substantial morbidity resulting from HIV infection. Likewise, the definition accepts a reactive screening test for HIV antibody without confirmation by a supplemental test because a repeatedly reactive screening test result, in combination with an indicator disease, is highly indicative of true HIV disease. For national surveillance purposes, the tiny proportion of possibly false-positive screening tests in persons with AIDSindicative diseases is of little consequence. For the individual patient, however, a correct diagnosis is critically important. The use of supplemental tests is, therefore, strongly endorsed. An increase in the diagnostic use of HIV-antibody tests could improve both the quality of medical care and the function of the new case definition, as well as assist in providing counselling to prevent transmission of HIV.

Page  8 0%_ MMWR August 14,1987 FIGURE I. Flow diagram for revised CDC case definition of AIDS, September 1,, 1987

Page  9 Vol. 361/ No.18 MMWR 9S References 1. World Health Organization. Acquired immunodeficiency syndrome (AIDS): WHO/CDC case definition for AIDS. WHO Wkly Epidemiol Rec 1986;61:69-72. 2. Haverkos HW, Gottlieb MS, Killen JY, Edelman R. Classification of HTLV-Ill/LAV-related diseases [Letter]. J Infect Dis 1985;162:1095. 3. Redfield RR, Wright DC, Tramont EC. The Walter Reed staging classification of HTLV-III infection. N EngI J Med 1986;314:131-2. 4. CDC. Classification system for human T-lymphotropic virus type III/lymphadenopathyassociated virus infections. MMWR 1986;35:334-9. 5. CDC. Classification system for human immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987;36:225-30,235. 6. Hardy AM, Starcher ET, Morgan WM, et al. Review of death certificates to assess completeness of AIDS case reporting. Pub HIth Rep 1987;102(4):386-91. 7. Starcher ET, Biel JK, Rivera-Castano R, Day JM, Hopkins SG, Miller JW. The impact of presumptively diagnosed opportunistic infections and cancers on national reporting of AIDS [Abstract]. Washington, DC: III International Conference on AIDS, June 1-5, 1987.

Page  10 10S MMWR August 14, 1987 APPENDIX I Laboratory Evidence For or Against HIV Infection 1. For Infection: When a patient has disease consistent with AIDS: a. a serum specimen from a patient >15 months of age, or from a child <15 months of age whose mother is not thought to have had HIV infection during the child's perinatal period, that is repeatedly reactive for HIV antibody by a screening test (e.g., enzyme-linked immunosorbent assay [ELISAJ), as long as subsequent HIV-antibody tests (e.g., Western blot, immunofluorescence assay), if done, are positive; OR b. a serum specimen from a child < 15 months of age, whose mother is thought to have had HIV infection during the child's perinatal period, that is repeatedly reactive for HIV antibody by a screening test (e.g., ELISA), plus increased serum immunoglobulin levels and at least one of the following abnormal immunologic test results: reduced absolute lymphocyte count, depressed CD4 (T-helper) lymphocyte count, or decreased CD4/CD8 (helper/suppressor) ratio, as long as subsequent antibody tests (e.g., Western blot, immunofluorescence assay), if done, are positive; OR c. a positive test for HIV serum antigen; OR d. a positive HIV culture confirmed by both reverse transcriptase detection and a specific HIV-antigen test or in situ hybridization using a nucleic acid probe; OR e. a positive result on any other highly specific test for HIV (e.g., nucleic acid probe of peripheral blood lymphocytes). 2. Against Infection: A nonreactive screening test for serum antibody to HIV (e.g., ELISA) without a reactive or positive result on any other test for HIV infection (e.g., antibody, antigen, culture), if done. 3. Inconclusive (Neither For nor Against Infection): a. a repeatedly reactive screening test for serum antibody to HIV (e.g., ELISA) followed by a negative or inconclusive supplemental test (e.g., Western blot, immunofluorescence assay) without a positive HIV culture or serum antigen test, if done; OR b. a serum specimen from a child < 15 months of age, whose mother is thought to have had HIV infection during the child's perinatal period, that is repeatedly reactive for HIV antibody by a screening test, even if positive by a supplemental test, without additional evidence for immunodeficiency as described above (in 1.b) and without a positive HIV culture or serum antigen test, if done.

Page  11 Vol. 36/ No. IS MMWR 118 APPENDIX II Definitive Diagnostic Methods for Diseases Indicative of AIDS Diseases Definitive Diagnostic Methods cryptosporidiosis cytomegalovirus isosporiasis Kaposi's sarcoma lymphoma lymphoid pneumonia or hyperplasia Pneumocystis carinl pneumonia progressive multifocal leukoencephalopathy toxoplasmosis candidiasis microscopy (histology or cytology). coccidioidomycosis cryptococcosis herpes simplex virus histoplasmosis tuberculosis other mycobacteriosis salmonellosis other bacterial infection gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a specimen obtained directly from the tissues affected (including scrapings from the mucosal surface), not from a culture. microscopy (histology or cytology), culture, or detection of antigen in a specimen obtained directly from the tissues affected or a fluid from those tissues. culture.

Page  12 12S MMWR August 14, 1987 HIV encephalopathy* (dementia) clinical findings of disabling cognitive and/or motor dysfunction interfering with occupation or activities of daily living, or loss of behavioral developmental milestones affecting a child, progressing over weeks to months, in the absence of a concurrent illness or condition other than HIV infection that could explain the findings. Methods to rule out such concurrent illnesses and conditions must include cerebrospinal fluid examination and either brain imaging (computed tomography or magnetic resonance) or autopsy. HIV wasting syndrome* findings of profound involuntary weight loss >10% of baseline body weight plus either chronic diarrhea (at least two loose stools per day for: 30 days) or chronic weakness and documented fever (for: 30 days, intermittent or constant) in the absence of a concurrent illness or condition other than HIV infection that could explain the findings (e.g., cancer, tuberculosis, cryptosporidiosis, or other specific enteritis). *For HIV encephalopathy and HIV wasting syndrome, the methods of diagnosis described here are not truly definitive, but are sufficiently rigorous for surveillance purposes.

Page  13 Vol. 36 I1No. iS MMWR 13S APPENDIX III Suggested Guidelines for Presumptive Diagnosis of Diseases Indicative of AIDS Presumptive Diagnostic Criteria Diseases candidiasis of esophagus cytomegalovirus retinitis mycobacteriosis Kaposi's sarcoma lymphoid interstitial pneumonia Pneumocystis carinii pneumonia a. recent onset of retrosternal pain on swallowing; AND b. oral candidiasis diagnosed by the gross appearance of white patches or plaques on an erythematous base or by the microscopic appearance of fungal mycelial filaments in an uncultured specimen scraped from the oral mucosa. a characteristic appearance on serial ophthalmoscopic examinations (e.g., discrete patches of retinal whitening with distinct borders, spreading in a centrifugal manner, following blood vessels, progressing over several months, frequently associated with retinal vasculitis, hemorrhage, and necrosis). Resolution of active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling. microscopy of a specimen from stool or normally sterile body fluids or tissue from a site other than lungs, skin, or cervical or hilar lymph nodes, showing acid-fast bacilli of a species not identified by culture. a characteristic gross appearance of an erythematous or violaceous plaque-like lesion on skin or mucous membrane. (Note: Presumptive diagnosis of Kaposi's sarcoma should not be made by clinicians who have seen few cases of it.) bilateral reticulonodular interstitial pulmonary infiltrates present on chest X ray for >2 months with no pathogen identified and no response to antibiotic treatment. a. a history of dyspnea on exertion or nonproductive cough of recent onset (within the past 3 months); AND b. chest X-ray evidence of diffuse bilateral interstitial infiltrates or gallium scan evidence of diffuse bilateral pulmonary disease; AND c. arterial blood gas analysis showing an arterial p02 Of <70 mm Hg or a low respiratory diffusing capacity (<80% of predicted values) or an increase in the alveolar-arterial oxygen tension gradient; AND d. no evidence of a bacterial pneumonia.

Page  14 14S MMWR August 14, 1987 toxoplasmosis of the brain a. recent onset of a focal neurologic abnormality consistent with intracranial disease or a reduced level of consciousness; AND b. brain imaging evidence of a lesion having a mass effect (on computed tomography or nuclear magnetic resonance) or the radiographic appearance of which is enhanced by injection of contrast medium; AND c. serum antibody to toxoplasmosis or successful response to therapy for toxoplasmosis.

Page  15 Vol. 36/No. IS MMWR 15-S APPENDIX IV Equivalent Terms and International Classification of Disease (lCD) Codes for AIDS-Indicative Lymphomas The following terms and codes describe lymphomas indicative of AIDS in patients with antibody evidence for HIV infection (Section II.A.8 of the AIDS case definition). Many of these terms are obsolete or equivalent to one another. ICD-9-CM (1978) Codes Terms 200.0 Reticulosarcoma lymphoma (malignant): histiocytic (diffuse) reticulum cell sarcoma: pleomorphic cell type or not otherwise specified 200.2 Burkitt's tumor or lymphoma malignant lymphoma, Burkitt's type ICD-O (Oncologic Histologic Types 1976) Codes Terms 9600/3 Malignant lymphoma, undifferentiated cell type non-Burkitt's or not otherwise specified 9601/3 Malignant lymphoma, stem cell type stem cell lymphoma 9612/3 Malignant lymphoma, immunoblastic type immunoblastic sarcoma, immunoblastic lymphoma, or immunoblastic lymphosarcoma 9632/3 Malignant lymphoma, centroblastic type diffuse or not otherwise specified, or germinoblastic sarcoma: diffuse or not otherwise specified 9633/3 Malignant lymphoma, follicular center cell, non-cleaved diffuse or not otherwise specified 9640/3 Reticulosarcoma, not otherwise specified malignant lymphoma, histiocytic: diffuse or not otherwise specified reticulum cell sarcoma, not otherwise specified malignant lymphoma, reticulum cell type 9641/3 Reticulosarcoma, pleomorphic cell type malignant lymphoma, histiocytic, pleomorphic cell type reticulum cell sarcoma, pleomorphic cell type 9750/3 Burkitt's lymphoma or Burkitt's tumor malignant lymphoma, undifferentiated, Burkitt's type malignant lymphoma, lymphoblastic, Burkitt's type

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