1506 cytomegalovirus and HIV but is likewise toxic. It is in an early investigational stage. For herpes simplex and herpes zoster infections, acyclovir is the agent of choice. Localised zosteriform lesions may not have to be treated; disseminated zoster almost always responds to 10 mg/kg 8-hourly. Herpes simplex virus has been associated with necrotising perianal lesions and there is a tendency for these lesions to recur. 5 mg/kg every 8 h parenterally or 1000 mg/day orally may be effective treatment against herpes simplex virus but recur- rences are to be expected. Prophylaxis of Opportunistic Infections in AIDS and AIDS-related Complex The infectious complications of HIV disease show a great tendency to recur. In AIDS-related complex, oral candidiasis will inevitably recur unless some maintenance suppression is provided, topically by clotrimazole or nystatin or systemically by ketoconazole. Similarly, in the absence of prophylaxis pneumocystis infection recurs in 30%-50% of patients within 6 months; this may happen despite antiviral therapy with zidovudine. Because patients who present with AIDS-lymphoma and Kaposi’s sarcoma are at high risk of eventual pneumocystis infection, many clinicians give drugs to prevent first infections. No large controlled studies have been undertaken, but chemopro- phylaxis is now recommended for this group. For indi- viduals who have already been infected with pneumocystis, prophylaxis seems especially desirable but presents diffi- culties because dermal hypersensitivity reactions to co- trimoxazole will have developed in many (perhaps the majority) during the initial course. If such reactions have not occurred, 160-320 mg co-trimoxazole can be administered twice daily. Some authorities feel that this must be given throughout the week and others have looked at intermittent prophylaxis for 3 out of 7 days a week, in a manner similar to that used to prevent pneumocystis infection in leukaemic children. Pentamidine may be given im or iv every one to four weeks and there has been considerable interest in delivery by aerosol. The approach is investigational but 60 mg bi-weekly as an aerosol may be effective prophylaxis. After an allergic reaction to co-trimoxazole one might hesitate to use other fixed combinations containing sulpho- namides, but in fact we and others find that the fixed combination of pyrimethamine with sulfadoxine (’Fansidar’ 1:20 combination) is tolerated by most patients who have had a reaction to co-trimoxazole.23 It is not clear whether folate-antagonist sulphonamide combinations such as co- trimoxazole will be effective in preventing toxoplasmosis. Once the patient has cryptococcal meningitis, cure is not a realistic consideration and suppressive therapy seems essen- tial to prevent relapse. Amphotericin bi-weekly in the usual therapeutic doses may be sufficient. For patients who cannot take amphotericin, ketoconazole in doses of 800-1200 mg may give short-term suppression. A new azole, fluconazole, has given promising results in the post-amphotericin phase but more clinical experience is required. REFERENCES 1 Gottlieb M, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men—evidence of a new acquired cellular immunodeficiency N Engl J Med 1981, 305: 1425-31 2 Hirsch MS, Kaplan JC Treatment of human immunodeficiency virus infections. Antimicrob Ag Chemother 1987; 31: 839-43 3 Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1987, 317: 186-98 4 Groopman JE Hematopoietic growth factors From methylcellulose to man. Cell 1987, 50: 5-6. 5. Young LS Management of opportunistic infections complicating the acquired immunodeficiency syndrome. Med Clin N Am 1986; 70: 677-92. 6. Suffredini AF, Ognibene FP, Lack EE, et al. Nonspecific interstitial pneumonitis A common cause of pulmonary disease in the acquired immunodeficiency syndrome. Ann Intern Med 1987, 107: 7-13 7. Murray JF, Garay SM, Hopewell PC, et al. Pulmonary complications of the acquired immunodeficiency syndrome An update Am Rev Respir Dis 1987; 135: 504-09 8 Polsky B, Gold JWM, Whimbey E, et al. Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986, 101: 641-45 9. Whimbey E, Gold JWM, Polsky B, et al Bacteremia and fungemia in patients with acquired immunodeficiency syndrome. Ann Intern Med 1986; 104: 511-14 10. Pitchenik AE, Cole, C, Russell BW, et al. Tuberculosis, atypical mycobacteriosis, and the acquired immunodeficiency syndrome among Haitian and non-Haitian patients in south Florida. Ann Intern Med 1984; 101: 641-45 11 Bradford AN, Petito CK, Gold JWM, et al Cerebral toxoplasmosis complicating the acquired immunodeficiency syndrome clinical and neuropathological findings in 27 patients. Ann Neurol 1986; 19. 224-38. 12. DeHovitz JA, Pape JW, Boncy M, Johnson WD Jr. Clinical manifestations and the therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N Engl J Med 1986; 315: 87-90 13. Current WL, Rose NC, Ernst JV, et al. Human cryptosporidiosis in immunocom- petent and immunodeficient persons-studies of an outbreak and experimental transmission. N Engl J Med 1983, 308: 1252-57. 14. Hawkins CC, Gold JWM, Whimbey E, et al. Mycobacterium avium complex infections in patients with the acquired immunodeficiency syndrome Ann Intern Med 1986; 105: 184-85. 15. Young LS, Inderlied C, Berling G, Gottlieb MS. Mycobacterial infections in AIDS patients with emphasis on M avium complex Rev Inf Dis 1986, 8: 1024-33 16. Baron EJ, Young LS Amikacin, ethambutol, and rifampin for treatment of disseminated Mycobacterium avium intracellulare infections in patients with acquired immune deficiency syndrome Diag Microb Infect Dis 1986, 5: 215-20. 17 Wharton JM, Coleman DL, Wofsy CB, et al. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105: 37-44. 18. Montgomery AB, Debs KJ, Luce JM, et al. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome Lancet 1987; ii: 480-83. 19. Leoung GS, Mills S, Hopewell PC, Hughes W, Wofsy C. Dapsone-trimethoprim for Pneumocystis carinu pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105: 45-48. 20. Golden JA, Sjoerdsma A, Santi DV; Pneumocystis carinii pneumonia treated with alpha-difluoromethylornithine. West J Med 1984; 141: 613-23. 21 Benntt JE, Dismukes WE, Duma RJ, et al A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979; 301: 126-31. 22. Collaborative DHPG treatment study group. Treatment of serious cytomegalovirus infections with 9-( 1,3-dihydroxy-2 propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med 1986, 314: 801-05 23 Gottlieb MS, Knight S, Mitsuyasu R, et al Prophylaxis of Pneumocystis carinii pneumonia is AIDS with pyrimethamine-sulfadoxine (Fansidar) Lancet 1984, ii 398-99. Epidemiology SEVERITY OF ILLNESS: CONCEPTS AND MEASUREMENTS RUTH E. K. STEIN ELLEN C. PERRIN I. BARRY PLESS STEVEN L. GORTMAKER JAMES M. PERRIN DEBORAH KLEIN WALKER MICHAEL WEITZMAN FOR THE RESEARCH CONSORTIUM ON CHRONIC ILLNESS IN CHILDHOOD ALTHOUGH it seems intuitively clear that diseases vary in severity, references to severity in published reports are inconsistent and vague. Most imply that it is quantifiable and that it reflects a biological absolute. The term is used to describe concepts as diverse as the underlying biological defect, the amount of illness or disability caused by a condition, the condition’s impact on quality of life, and the financial, social, or emotional burden imposed by the illness.1-5 These notions sometimes overlap, but often they hardly relate to one another at all. This paper has four aims: to clarify some of the constructs of severity of illness and propose a new framework for classifying existing measures, to examine issues in the assessment of all forms of severity; to