Case Definition of AIDS

Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome

AIDS Program Center for Infectious Diseases Centers for Disease Control Atlanta, Georgia 30333

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(suppl no. 1S):(inclusive page numbers).

Centers for Disease Control James O. Mason, M.D., Dr.P.H., Director

Center for Infectious Diseases Frederick A. Murphy, D.V.M., Ph.D., Acting Director

AIDS Program James W. Curran, M.D., Director

This report was prepared by: 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.

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 I.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 less than 15 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 less than 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 application of the revised definition to patients already reported to health departments. The new definition follows:

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 I) and the patient had no other cause of immunodeficiency listed in Section I.A below, then any disease listed in Section I.B indicates AIDS if it was diagnosed by a definitive method (See Appendix II).

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 less than or equal to 3 months before the onset of the indicator disease 2. any of the following diseases diagnosed less than or equal to 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 greater than 1 month 4. cytomegalovirus disease of an organ other than liver, spleen, or lymph nodes in a patient greater than 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 greater than 1 month of age 6. Kaposi's sarcoma affecting a patient less than 60 years of age 7. lymphoma of the brain (primary) affecting a patient less than 60 years of age 8. lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia (LIP/PLH complex) affecting a child less than 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 greater than 1 month of age

II. With Laboratory Evidence for HIV Infection

Regardless of the presence of other causes of immunodeficiency (I.A), in the presence of laboratory evidence for HIV infection (See Appendix I), any disease listed above (I.B) or below (II.A or II.B) indicates a diagnosis of AIDS.

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 less than 13 years of age: 03 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 greater than 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, large- cell 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 "lymphocytic," "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 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 III. 1. candidiasis of the esophagus 2. cytomegalovirus retinitis with loss of vision 3. Kaposi's sarcoma 4. lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperxpDlasia (LIP/PLH complex) affecting a child less than 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 greater than 1 month of age

III. With Laboratory Evidence Against HIV Infection

With laboratory test results negative for HIV infection (See Appendix I), a diagnosis of AIDS for surveillance purposes is ruled out unless:

A. all the other causes of immunodeficiency listed above in Section I.A 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 I.B diagnosed by a definitive method (See Appendix II); AND b. a T-helper/inducer (CD4) lymphocyte count less than 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 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, less than 7% have been reported with HIV-antibody test results, compared with greater than 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 HIV- antibody 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 AIDS- indicative 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.

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- III/LAV-related diseases (Letter). J Infect Dis 1985;152:1095.
3. Redfield RR, Wright DC, Tramont EC. The Walter Reed staging classification of HTLV-III infection. N Engl J Med 1986;314:131-2.
4. CDC. Classification system for human T-lymphotropic virus type III/lymphadenopathy- associated 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 Hlth 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.

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 greater than or equal to 15 months of age, or from a child less than 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 (ELISA)), 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 less than 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 less than 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.

APPENDIX II Definitive Diagnostic Methods for Diseases Indicative of AIDS

Diseases Definitive Diagnostic Methods cryptosporidiosis cytomegalovirus isosporiasis Kaposi's sarcoma lymphoma, lymphoid pneumonia microscopy (histology or cytology). or hyperplasia Pneumocystis carinii pneumonia progressive multifocal leukoencephalopathy toxoplasmosis candidiasis 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. coccidioidomycosis microscopy (histology or cytology), culture, or cryptococcosis detection of antigen in a specimen obtained herpes simplex virus directly from the tissues affected or a fluid histoplasmosis from those tissues. tuberculosis other mycobacteriosis salmonellosis culture. other bacterial infection

HIV encephalopathy* clinical findings of disabling cognitive and/or (dementia) 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.

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