Click for next page ( 203


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 202
B CDC Classification System for HIV Infections and Revised Case Definition for AIDS CDC Classification System for HIV Infections* INTRODUCTION Persons infected with the etiologic retrovirus of acquired immunodeficiency syndrome (AIDS) ( 1-4 ). may present with a variety of manifestations ranging from asymptomatic infec- tion to severe immunodeficiency and life-threatening secondary infectious diseases or can- cers. The rapid growth of knowledge about human T-lymphotropic virus type 111/ Iymphadenopathy-associated virus (HTLV-111/LAV) has resulted in an increasing need for a system of classifying patients within this spectrum of clinical and laboratory findings attri- butable to HTLV-111/LAV infection (5- 7). Various means are now used to describe and assess patients with manifestations of HTLV-111/LAV infection and to describe their signs, symptoms, and laboratory findings. The surveillance definition of AIDS has proven to be extremely valuable and quite reliable for some epidemiologic studies and clinical assessment of patients with the more severe manifestations of disease. However, more inclusive definitions and classifications of HTLV-111/LAV infection are needed for optimum patient care, health planning, and public health control strategies, as well as for epidemiologic studies and special surveys. A broadly applicable, easily understood classification system should also facilitate and clarify communication about this disease. In an attempt to formulate the most appropriate classification system, CDC has sought the advice of a panel of expert consultants" to assist in defining the manifestations of HTLV-111/ LAV infection. GOALS AND OBJECTIVES OF THE CLASSIFICATION SYSTEM The classification system presented in this report is primarily applicable to public health purposes, including disease reporting and surveillance, epidemiologic studies, prevention and control activities, and public health policy and planning. The AIDS virus has been variously termed human T-lymphotropic virus type 111 (HTLV-111), Iymphadenopathy-associated virus (LAV), AlDS-associated retrovirus (ARV), or human immunodeficien- cy virus (HIV). The desigr~ation human immunodeficiency virus (HIV) has recently been proposed by a subcommittee of the International Committee for the Taxonomy of Viruses as the appropriate name for the retrovirus that has been implicated as the causative agent of AIDS (4 ). tThe following persons served on the review panel: DS Burke, MD, RR Redfield, MD, Walter Reed Army Institute of Research, Washington, DC; J Chin, MD, State Epidemiologist, California Department of Health Services. LZ Cooper, MD, St Luke's-Roosevelt Hospital Center, New York City; JP Davis, MD, State Epidemiologist, Wisconsin Division of Health; MA Fischl, MD, University of Miami School of Medi- cine, Miami, Florida; G Friedland, MD, Albert Einstein College of Medicine, New York City; MA Johnson, MD, Dl Abrams, MD, San Francisco General Hospital; D Mildvan, MD, Beth Israel Medical Center, New York City; CU Tuazon, MD, George Washington University School of Medicine, Washington, DC; RW Price, MD, Memorial Sloan-Kettering Cancer Center, New York City; C Konigsberg, MD, Broward County Public Health Unit, Fort Lauderdale, Florida; MS Gottlieb, MD, University of CaliforniaLos Angeles Medical Center; representatives of the National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institutes of Health, Center for Infectious Diseases, CDC. SOURCE: Reprinted from Morbidity and Mortality Weekly Report 35 (May 23, 1986):334-339. 202

OCR for page 202
APPENDIX B 203 Immediate applications of such a system include the classification of infected persons for reporting of cases to state and local public health agencies, and use in various disease coding and recording systems, such as the forthcoming 1 0th revision of the International Classifica- t~n of Diseases. DEFINITION OF HTLV-111/LAV INFECTION The most specific diagnosis of HTLV-111/LAV infection is by direct identification of the virus in host tissues by virus isolation; however, the techniques for isolating HTLV-liliLAV cur- rently lack sensitivity for detecting infection and are not readily available. For public health purposes, patients with repeatedly reactive screening tests for HTLV-111/LAV antibody (e.g., enzyme-linked immunosorbent assay) in whom antibody is also identified by the use of sup- plemental tests (e.g., Western blot, immunofluorescence assay) should be considered both in- fected and infective ( 8- 10 ). Although HTLV-111/LAV infection is identified by isolation of the virus or, indirectly, by the preserve of antibody to the virus a presumptive clinical diagnosis of HTLV-111/LAV infection has been made in some situations in the absence of positive virologic or serologic test results. There is a very strong correlation between the clinical manifestations of AIDS as defined by CDC and the presence of HTLV-111/LAV antibody ( 1 1-14 I. Most persons whose clinical illness fulfills the CDC surveillance definition for Al :)S will have been infected with the virus ( 12-14 ). CLASSIFICATION SYSTEM This system classifies the manifestations of HTLV-IIIILAV infection into four mutually ex- clusive groups, designated by Roman numerals I through IV (Table 5). The classification system applies only to pat/ems diagnosed as havmg HTLV-III/LAV infection (see previous sec- tion, DEFINITION OF HTLV-IIIfLAV INFECTION). Classification in a particular group is not explicitly intended to have prognostic significance, nor to designate severity of illness. Howev- er, classification in the four principal groups, I-IV, is hierarchical in that persons classified in a particular group should not be reclassified in a preceding group if clinical findings resolve, since clinical improvement may not accurately reflect changes in the severity of the underlying disease. Ares ~ Or ~~.~ ...: 4~ :__^ _:___ ~rou,~ ~ ~r~c~uaes patients warn transient signs ano symptoms that appear at the time of, or shortly after, initial infection with HTLV-111/LAV as identified by laboratory studies. All patients in Group I will be reclassified in another group following resolution of this acute syndrome. TABLE 5. Summary of classification system for human T-lymphotropic virus type 111/ I ymphadenopath y-associated virus Group 1. Acute infection Group 11. Asymptomatic infection Group 111. Persistent generalized Iymphadenopathye Group IV. Other disease Subgroup A. Constitutional disease Subgroup B. Neurologic disease Subgroup C. Secondary infectious diseases Category C-1. Specified secondary infectious diseases listed in the CDC surveillance definition for AlDSt Category C-2. Other specified secondary infectious diseases Subgroup D. Secondary cancers" Subgroup E. Other conditions Patients in Groups 11 and 111 may be subclassified on the basis of a laboratory evaluation. "includes those patients whose clinical presentation fulfills the definition of AIDS used by CDC for na- tional reporting.

OCR for page 202
204 APPENDIX B Group 11 includes patients who have no signs or symptoms of HTLV-111/LAV infection. Pa- tients in this category may be subclassified based on whether hematologic and/or immuno- logic laboratory studies have been done and whether results are abnormal in a manner consis- tent with the effects of HTLV-111/LAV infection. Group 111 includes patients with persistent generalized Iymphadenopathy, but without find- ings that would lead to classification in Group IV. Patients in this category may be subclassi- fied based on the results of laboratory studies in the same manner as patients in Group 11. Group IV includes patients with clinical symptoms and signs of HTLV-111/LAV infection other than or in addition to Iymphadenopathy. Patients in this group are assigned to one or more subgroups based on clinical findings. These subgroups are: A. constitutional disease; B. necrologic disease; C. secondary infectious diseases; D. secondary cancers; and E. other conditions resulting from HTLV-111/LAV infection. There is no a priori hierarchy of severity among subgroups A through E, and these subgroups are not mutually exclusive. Definitions of the groups and subgroups are as follows: Group 1. Acute HTLV-111/LAV Infection. Defined as a mononucleosis-like syndrome, with or without aseptic meningitis, associated with seroconversion for HTLV-liliLAV antibody ( 15-16). Antibody seroconversion is required as evidence of initial infection; current viral iso- lation procedures are not adequately sensitive to be relied on for demonstrating the onset of infection. Group 11. Asymptomatic HTLV-111/LAV Infection. Defined as the absence of signs or symptoms of HTLV-IIIILAV infection. To be classified in Group 11, patients must have had no previous signs or symptoms that would have led to classification in Groups 111 or IV. Patients whose clinical findings caused them to be classified in Groups 111 or IV should not be reclassi- fied in Group 11 if those clinical findings resolve. Patients in this group may be subclassified on the basis of a laboratory evaluation. Labora- tory studies commonly indicated for patients with HTLV-111/LAV infection include, but are not limited to, a complete blood count (including differential white blood cell count) and a platelet count. Immunologic tests, especially T-lymphocyte helper and suppressor cell counts, are also an important part of the overall evaluation. Patients whose test results are within normal limits, as well as those for whom a laboratory evaluation has not yet been completed, should be differentiated from patients whose test results are consistent with defects associated with HTLV-Ili/LAV infection (e.g., Iymphopenia, thrombocytopenia, decreased number of helper [Td,3 T-lymphocytes). Group IIJ. Persistent Generalized Lymphadenopathy (PGL). Defined as palpable Iym- phadenopathy (Iymph node enlargement of 1 cm or greater) at two or more extra-inguinal sites persisting for more than 3 months in the absence of a concurrent illness or condition other than HTLV-111/LAV infection to explain the findings. Patients in this group may also be subclassified on the basis of a laboratory evaluation, as is done for asymptomatic patients in Group 11 (see above). Patients with PGL whose clinical findings caused them to be classified in Group IV should not be reclassified in Group 111 if those other clinical findings resolve. Group IV. Other HTLV-111/LAV Disease. The clinical manifestations of patients in this group may be designated by assignment to one or more subgroups (A-E) listed below. Within Group IV, subgroup classification is independent of the presence or absence of Iymphade- nopathy. Each subgroup may include patients who are minimally symptomatic, as well as pa- tients who are severely ill. Increased specificity for manifestations of HTLV-111/LAV infection, if needed for clinical purposes or research purposes or for disability determinations, may be achieved by creating additional divisions within each subgroup.

OCR for page 202
APPENDIX B 205 Subgroup A. Constitutional disease. Defined as one or more of the following: fever per- sisting more than 1 month, involuntary weight loss of greater than 10% of baseline, or diar- rhea persisting more than 1 month; and the absence of a concurrent illness or condition other than HTLV-111/LAV infection to explain the findings. Subgroup B. Nourologic dise~o. Defined as one or more of the following: dementia, myelopathy, or peripheral neuropathy; and the absence of a concurrent illness or condition other than HTLV-111/LAV infection to explain the findings. Subgroup C. Secondary infectious diseases. Defined as the diagnosis of an infectious disease associated with HTLV-111/LAV infection and/or at least moderately indicative of a defect in cell-mediated immunity. Patients in this subgroup are divided further into two categories: Category C- 1. Includes patients with symptomatic or invasive disease due to one of 1 2 specified secondary infectious diseases listed in the surveillance definition of AIDS: Pneumocystis carinii pneumonia, chronic cryptosporidiosis, toxoplasmosis, extra- intestinal strongyloidiasis, isosporiasis, candidiasis (esophageal, bronchial, or pulmo- nary), cryptococcosis, histoplasmosis, mycobacterial infection with Mycobacterium avium comple% or M kansasi`, cytomegalovirus infection, chronic mucocutaneous or disseminated herpes simplex virus infection, and progressive multifocal leukoen- cephalopathy. Category C-2. Includes patients with symptomatic or invasive disease due to one of six other specified secondary infectious diseases: oral hairy leukoplakia, multidermatomal herpes poster, recurrent Salmonella bacteremia, nocardiosis, tuberculosis, or oral can- didiasis (thrush). Subgroup D. Secondary cancers. Defined as the diagnosis of one or more kinds of cancer known to be associated with HTLV-111/LAV infection as listed in the surveillance definition of AIDS and at least moderately indicative of a defect in cell-mediated immunity: Kaposi's sarcoma, non-Hodgkin's Iymphoma (small, noncleaved Iymphoma or immunoblastic sarco- ma), or primary Iymphoma of the brain. Subgroup E. Other conditions in HTLV-111/LAV infection. Defined as the presence of other clinical findings or diseases, not classifiable above, that may be attributed to HTLV-111/ LAV infection and/or may be indicative of a defect in cell-mediated immunity. Included are patients with chronic Iymphoid interstitial pneumonitis. Also included are those patients whose signs or symptoms could be attributed either to HTLV-111/LAV infection or to another coexisting disease not classified elsewhere, and patients with other clinical illnesses, the course or management of which may be complicated or altered by HTLV-111/LAV infection. Examples include: patients with constitutional symptoms not meeting the criteria for sub- group IV-A; patients with infectious diseases not listed in subgroup IV-C; and patients with neoplasms not listed in subgroup IV-D. Reported by Center for Infectious Diseases, CDC. Editorial Note: The classification system is meant to provide a means of grouping patients infected with HTLV-111/LAV according to the clinical expression of disease. It will require periodic revision as warranted by new information about HTLV-111/LAV infection. The defini- This subgroup includes patients with one or more of the specified infectious diseases listed whose clinical presentation fulfills the definition of AIDS as used by CDC for national reporting. This subgroup includes those patients with one or more of the specified cancers listed whose clinical presentation fulfills the definition of AIDS as used by CDC for national reporting.

OCR for page 202
206 APPENDIX B tion of particular syndromes will evolve with increasing knowledge of the significance of cer- tain clinical findings and laboratory tests. New diagnostic techniques, such as the detection of specific HTLV-111/LAV antigens or antibodies, may add specificity to the assessment of pa- tients infected with HTLV-111/LAV. The classification system defines a limited number of specified clinical presentations. Pa- tients whose signs and symptoms do not meet the criteria for other groups and subgroups, but whose findings are attributable to HTLV-111/LAV infection, should be classified in sub- group IV-E. As the classification system is revised and updated, certain subsets of patients in subgroup IV-E may be identified as having related groups of clinical findings that should be separately classified as distinct syndromes. This could be accomplished either by creating additional subgroups within Group IV or by broadening the definitions of the existing sub- groups. Persons currently using other classification systems (6-7) or nomenclatures (e.g., AIDS- related complex, Iymphadenopathy syndrome) can find equivalences with those systems and terminologies and the classification presented in this report. Because this classification system has only four principal groups based on chronology, presence or absence of signs and symptoms, and the type of clinical findings present, comparisons with other classifications based either on clinical findings or on laboratory assessment are easily accomplished. This classification system does not imply any change in the definition of AIDS used by CDC since 1 981 for national reporting. Patients whose clinical presentations fulfill the surveil- lance definition of AIDS are classified in Group IV. However, not every case in Group IV will meet the surveillance definition. Persons wishing to comment on this material are encouraged to send comments in writing to the AIDS Program, Center for Infectious Diseases, CDC. References 1. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retrovi- ruses (HTLV-111) from patients with AIDS and at risk for AIDS. Science 1984;224:500-3. Barre-Sinoussi F. Chermann JC, Rey F. et al. Isolation of a T-lymphotropic retrovirus from a patient a+ risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71. Levy JA, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oshiro LS. Isolation of Iymphocy- topathic retroviruses from San Francisco patients with AIDS. Science 1984;225:840-2. 4. Coffin J. Haese A, Levy JA, et al. Human immunodeficiency viruses [Letter]. Science 1986;232: 697. 5. CDC. Revision of the case definition of acquired immunodeficiency syndrome for national re- portingUnited States. MMWR 1985;34:373-5. 6. Haverkos HW, Gottlieb MS, Killen JY, Edelman R. Classification of HTLV-111/LAV-related diseases [Letter]. J Infect Dis 1985;152: 1095. 7. Redfield RR, Wright DC, Tramont EC. The Walter Reed staging classification for HTLV-111/LAV infec- tion. N Engl J Med 1 986;314:1 31 -2. 8. CDC. Antibodies to a retrovirus etiologically associated with acquired immunodeficiency syndrome (AIDS) in populations with increased incidences of the syndrome. MMWR 1984;33:377-9. 9. CDC. Update: Public Health Service Workshop on Human T-Lymphotropic Virus Type 111 Antibody TestingUnited States. MMWR 1 985;34:477-8. 10. CDC. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type III/lymphadenopathy-associated virus. MMWR 1986;35: 152-5. 11. Selik RM, Haverkos HW, Curran JW. Acquired immune deficiency syndrome (AIDS) trends in the United States, 1978-1982. Am J Med 1984;76:493-500. Sarngadharan MG, Popovic M, Bruch L, Schupbach J. Gallo RC. Antibodies reactive with human T- lymphotropic retroviruses (HTLV-111) in the serum of patients with AIDS. Science 1984;224:506-8. 13. Safai B. Sarngadharan MG, Groopman JE, et aL Seroepidemiological studies of human T- lymphotropic retrovirus type 111 in acquired immunodeficiency syndrome. Lancet 1984;1:1438-40. 14. Laurence J. Brun-Vezinet F. Schutzer SE, et al. Lymphadenopathy associated viral antibody in AIDS. Immune correlations and definition of a carrier state. N Engl J Med 1984;31 1: 1269-73. 15. Ho DD, Sarngadharan M5, Resnick L, Dimarzo-Veronese F, Rota TR, Hirsch MS. Primary human T- lymphotropic virus type 111 infection. Ann Intern Med 1 985;103:880-3. 16. Cooper DA, Gold J, Maclean P, et al. Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. Lancet 1985;1:537-40. 3

OCR for page 202
APPENDIX B 207 Revision of the CDC Surveillance Case Definition for AIDS* INTRODUCTION The following revised case definition for surveillance of acquired immunodefi- ciency 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 confirm- atory laboratory evidence, diagnosis of AlDS-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 AlDS-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 Iymphoid interstitial pneumonia/pulmonary Iymphoid hyperplasia are accepted as indicative of AIDS among children but not among adults. Second, for children<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 < 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 applica- tion of the revised definition to patients already reported to health departments. The new definition follows: *Reported by Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases, CDC. SOURCE: Reprinted from Morbidity and Mortaliry Weekly Report 36, suppl. IS (August 14, 1987):3S-1SS.

OCR for page 202
208 APPENDIX B 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. 1. 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 l.A below, then any disease listed in Section l.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 immuno- suppressive/cytotoxic therapy ~3 months before the onset of the indicator disease any of the following diseases diagnosed ~3 months after diagnosis of the indicator disease: Hodgkin's disease, non-Hodgkin's Iymphoma (other than primary brain Iymphoma), Iymphocytic leukemia, multiple myeloma, any other cancer of Iymphoreticular or histiocytic tissue, or angioimmu- noblastic Iymphadenopathy a genetic (congenital) immunodeficiency syndrome or an acquired immu- nodeficiency 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: - - - 4. 2. 3. cryptosporidiosis with diarrhea persisting >1 month . . . .. . . . 5. cytomegatov~rus disease of an organ other than liver, spleen, or lymph nodes in a patient >1 month of age herpes simplex virus infection causing a mucocutaneous ulcer that per- sists 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. Iymphoma of the brain (primary) affecting a patient < 60 years of age 8. Iymphoid interstitial pneumonia and/or pulmonary Iymphoid hyperplasia (LIP/PLH complex) affecting a child <13 years of age 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 11. With Laboratory Evidence for HIV Infection Regardless of the presence of other causes of immunodeficiency (/.AJ, in the presence of laboratory evidence for HIV infection (See Appendix D, any disease listed above (I.B) or below (II.A or II.B) indicates a diagnosis of AIDS.

OCR for page 202
APPENDIX B 209 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 Iymph 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 Iymph nodes) 5. isosporiasis with diarrhea persisting >1 month 6. Kaposi's sarcoma at any age 7. Iymphoma of the brain (primary) at any age 8. other non-Hodgkin's Iymphoma of B-cell or unknown immunologic phe- notype and the following histologic types: a. small noncleaved Iymphoma (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 ) immunoblastic sarcoma (equivalent to any of the following, although not necessarily all in combination: immunoblastic Iymphoma, large- cell Iymphoma, diffuse histiocytic Iymphoma, diffuse undifferentiated Iymphoma, or high-grade Iymphoma) (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 immuno- logic phenotype or their histologic type is not described or is described as "Iymphocytic," "Iymphoblastic," "small cleaved," or "plasmacytoid Iym- phocytic" 9. any mycobacterial disease caused by mycobacteria other than M. tuber- culosis, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar Iymph nodes) 10. disease caused by M. tuberculosis, extrapulmonary (involving at least one site outside the lungs, regardless of whether there is concurrent pulmo- nary involvement) 11. Salmonella (nontyphoid) septicemia, recurrent 12. HIV wasting syndrome (emaciation, "slim disease") (See Appendix II for descri ption ) 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

OCR for page 202
210 APPENDIX B 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. Guide- lines for presumptive diagnoses are suggested in Appendix lilt 1. candidiasis of the esophagus 2. cytomegalovirus retinitis with loss of vision 3. Kaposi!s sarcoma 4. Iymphoid interstitial pneumonia and/or pulmonary Iymphoid hyperplasia (LIP/PLH complex) affecting a child <13 years of age 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 pneu mania 7. toxoplasmosis of the brain affecting a patient >1 month of age 111. With Laboratory Evidence Against HIV Infection With laboratory test results negative for HIV infection (See Appendix b, a diagnosis of AIDS for surveillance purposes is ruled out unless: A. all the other causes of immunodeficiency listed above in Section l.A are excluded; AND B. the patient has had either: 1. Pneumocystis carinii pneumonia diagnosed by a definitive method (See Appendix Il); OR 2. a. any of the other diseases indicative of AIDS listed above in Section l.B diagnosed by a definitive method (See Appendix Il); 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, pro- vided 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 HlV-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., encephalop- athy, wasting syndrome) affecting a substantial number of HlV-infected patients were not subject to epidemiologic surveillance, as they were not included in the AIDS

OCR for page 202
APPENDIX B 21 ~ case definition. For reporting purposes, the revision adds to the definition most of those severe non-infectious, non-cancerous HlV-associated conditions that are cate- gorized in the CDC clinical classification systems for HIV infection among adults and children (4,5 ). Another limitation of the old definition was that AlDS-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 HlV-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 HlV-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 geograph- ically, 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 HlV-antibody test but have an AlDS-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 HlV-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.

OCR for page 202
2 ~ 2 APPENDIX B FIGURE I. Flow diagram for revised CDC case definition of AIDS, September 1, 1987 , (_ Laboratory evidence of HIV infection (Appendix 1) Unknown or Inconclusive Are there other causes of immunodeficienc (Section l.A) Off BY - YES NO ~ _ Has any disease in Section l.B been definitively diagnosed (Appendix 11) ? ~- YES C ~ ~ Not a Case ,, gyp | Positive | Has any disease in Sections l.B or II.A been definitively diagnosed (Appendix 11) ? YES, @. '1, ('Not a Case] Has any disease in Section II.B been presumptively diagnosed (Appendix lil) ? YES~ Are there other causes of immunodeficienc l (Section l.A) YES NO YESES_ ' 1 NO 0~ 1N , ~ . ~ Not a Case ~ Has Pneurnocystis cannti pneumonia been definitively diagnosed (Appendix 11) Has any other disease in Section l.B been definitively diagnosed (Appendix 11) N:/ ( Not a Case) ?- ~5 New ~ ~ _ (Not a Case] , . ~ , __ @lY Is the T-helper lymphocyte count <400/mm3 ? YES

OCR for page 202
APPENDIX B 213 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, Kitten JY, Edelman R. Classification of HTLV-111/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. 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 complete- ness of AIDS case reporting. Pub Hlth Rep 1987;102(4):386-91. 7. Starcher ET, Biel JK, Rivera-Castano R. Day JM, Hopkins SO, Miller JW. The impact of presumptively diagnosed opportunistic infections and cancers on national reporting of AIDS [Abstract]. Washington, DC: lil International Conference on AIDS, June 1-5, 1987. APPENDIX I Laboratory Evidence For or Against HIV Infection 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 [ELISA]), as long as subsequent HlV-antibody tests (e.g., Western blot, immunofluorescence as- say), if done, are positive; OR 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 Iymphocyte count, depressed C[)4 (T-helper) Iymphocyte 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 a positive test for HIV serum antigen; OR d. a positive HIV culture confirmed by both reverse transcriptase detection and a specific HlV-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 Iymphocytes). c. 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.

OCR for page 202
214 APPENDIX B ~. 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 supplemen- tal 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 t' Definitive Diagnostic Methods for Diseases Indicative of AIDS Diseases cryptosporidiosis \ cytomegalovirus . . . . sosporlasls I Kaposi's sarcoma / Iymphoma | Iymphoid pneumonia or hyperplasia Pneumocystis carinii pneumonia progressive multifocal leu koencepha lopathy toxoplasmosis candidiasis . . . . coccldloldomycosls cryptococcosis herpes simplex virus histoplasmosis tu bercu losis other mycobacteriosis salmonellosis other bacterial infection Definitive Diagnostic Methods microscopy (histology or cytology). 1 gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a specimen obtained directly from the tissues affected (in- cluding 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.

OCR for page 202
APPENDIX B 2 ~ 5 HIV encephalopathy* \ (dementia) HIV wasting syndrome* clinical findings of disabling cognitive and/or ~ motor dysfunction interfering with occupation or / activities of daily living, or loss of behavioral de- velopmental milestones affecting a child, progressing over weeks to months, in the ,> absence of a concurrent illness or condition other l than HIV infection that could explain the findings. \ Methods to rule out such concurrent illnesses and l conditions must include cerebrospinal fluid exam- | ination and either brain imaging (computed to- mography or magnetic resonance) or autopsy. l 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, cryptosporidi- osis, 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. APPENDIX It! Suggested Guidelines for Presumptive Diagnosis of Diseases Indicative of AIDS Diseases candidiasis of esophagus Presumptive Diagnostic Criteria 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 fila- ments in an uncultured specimen scraped from the oral mucosa. cytomegalovirus a characteristic appearance on serial ophthalmoscopic retinitis 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 mot- tling.

OCR for page 202
2 ~ 6 APPENDIX B mycobacteriosis 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. Kaposi's a characteristic gross appearance of an erythematous or sarcoma violaceous plaque-like lesion on skin or mucous membrane. (Note: Presumptive diagnosis of k;aposi's sarcoma should not be made by clinicians who have seen few cases of it.) Iymphoid bilateral reticuJonodular interstitial pulmonary infiltrates interstitial present on chest X ray for ~2 months verity no pathogen pneumonia identified and no response to antibiotic treatment. Pneumocystis a. a history of dyspnea on exertion or nonproductive carinii cough of recent onset (within the past 3 months); AND pneumonia b. chest X-ray evidence of diffuse bilateral interstitial infil- trates or gallium scan evidence of diffuse bilateral pul- monary disease; AND c. arterial blood gas analysis showing an arterial PO2 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. toxoplasmosis a. recent onset of a focal necrologic abnormality consis- of the brain tent with intracranial disease or a reduced level of con- sciousness; AND b. brain imaging evidence of a lesion having a mass ef- fect (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.

OCR for page 202
APPENDIX B 217 APPENDIX IV Equivalent Terms and International Classification of Disease {ICD) Codes for AlDS-lndicative Lymphomas The following terms and codes describe Iymphomas 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. Codes 200.0 200.2 Codes 9600/3 960 1/3 96 1 2/3 9632/3 9633/3 9640/3 9641/3 9750/3 ICD-9-CM (1978) Terms Reticulosarcoma Iymphoma (malignant): histiocytic (diffuse) reticulum cell sarcoma: pleomorphic cell type or not otherwise specified Burkitt's tumor or Iymphoma malignant Iymphoma, Burkitt's type ICD-O (Oncologic Histologic Types 19761 Terms Malignant Iymphoma, undifferentiated cell type non-Burkitt's or not otherwise specified Malignant Iymphoma, stem cell type stem cell Iymphoma Malignant Iymphoma, immunoblastic type immunoblastic sarcoma, immunoblastic Iymphoma, or immunoblas- tic Iymphosarcoma Malignant Iymphoma, centroblastic type diffuse or not otherwise specified, or germinoblastic sarcoma: diffuse or not otherwise specified Malignant Iymphoma, follicular center cell, non-cleaved diffuse or not otherwise specified Reticulosarcoma, not otherwise specified malignant Iymphoma, histiocytic: diffuse or not otherwise specified reticulum cell sarcoma, not otherwise specified malignant Iymphoma, reticulum cell type Reticulosarcoma, pleomorphic cell type malignant Iymphoma, histiocytic, pleomorphic cell type reticulum cell sarcoma, pleomorphic cell type Burkitt's Iymphoma or Burkitt's tumor malignant Iymphoma, undifferentiated, Burkitt's type malignant Iym- phoma, Iymphoblastic, Burkitt's type