AIDS Information Newsletter 11/5/93 AIDS INFORMATION NEWSLETTER Michael Howe, MSLS, Editor AIDS Information Center VA Medical Center, San Francisco (415) 221-4810 ext 3305 November 5, 1993 TUBERCULOSIS AND HIV INFECTION (Part VI) CDC ADVISES CAUTION WITH BCG FOR IMMUNOCOMPROMISED PATIENTS BCG (bacillus of Calmette Guerin) vaccine is not routinely recommended for use in the United States for prevention of tuberculosis, the federal Centers for Disease Control and Prevention in Atlanta reiterated in recommendations on the use of vaccines and immune globulins in patients with altered immunocompetence (CDC. Recommendations of the advisory committee on immunization practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993;42(No. RR-4):[pages inclusive]). BCG should be administered with caution to persons in groups at high risk for HIV infection or persons known to be severely immunocompromised. Although limited data suggest that the vaccine may be safe for asymptomatic children infected with HIV, BCG vaccination is not recommended for HIV-infected adults or for persons with symptomatic disease, the CDC states. Vaccination should be restricted to persons at exceptionally high risk for tuberculosis. BCG vaccine is strongly recommended, however, for infants and children with negative tuberculin skin tests who are at high risk of intimate and prolonged exposure to persistently untreated or ineffectively treated patients with infectious pulmonary TB, the CDC advises. BCG is also recommended for those continuously exposed to persons with TB resistant to isoniazid and rifampin. In addition, BCG is recommended for tuberculin-negative infants and children in groups in which the rate of new infections exceeds 1% per year and for whom the usual surveillance and treatment programs have been attempted but are not operationally feasible. In the same report, the CDC reminds that killed or inactivated vaccines do not represent a danger to immunocompromised persons and generally should be administered as recommended for healthy persons. For specific immunocompromising conditions (e.g., asplenia), such patients may be at higher risk for certain disease, and additional vaccines, particularly bacterial polysaccharide vaccines (haemophilus influenzae type b (HIV), pneumococcal, and meningococcal), are recommended for them. Frequently, the immune response of immunocompromised persons to these vaccine antigens is not as good as that of immunocompetent persons and higher doses or more frequent boosters may be required. The degree to which an individual patient is immunocompromised should be determined by a physician. Severe immunosuppression can be due to a variety of conditions, including congenital immunodeficiency, HIV infection, leukemia, lymphoma, generalized malignancy or therapy with alkylating agents, antimetabolites, radiation, or large amounts of corticosteroids. For some of those conditions, all affected persons will be severely immunocompromised, while for others such as HIV infection, the spectrum of disease severity due to disease or treatment stage will determine the degree to which the immune system is compromised, the CDC reported. (MMWR Update. Hospital Infection Control. 1993 July;20(7):101-2.) DRUG-RESISTANT TB Strains of TB that are resistant to at least one conventional anti-TB drug are cause for significant concern because they are more life-threatening and complicated to treat than drug-sensitive TB strains. Resistant strains most commonly show resistance to a single drug, but multiple drug-resistant (MDR) TB strains, which are even more difficult to treat, are increasing in prevalence. Drug-resistant TB strains have developed primarily as a result of the failure of people undergoing drug treatment to follow the entire prescribed regimen of TB drug therapies. Inadequately prescribed regimens also lead to drug-resistant strains. As a result of inadequate treatment, naturally occurring mutant strains emerge. These strains can be transmitted by people with active, pulmonary TB. While treatment for drug-sensitive TB strains can be complete in a year or less with an efficacy of nearly 100%, someone with a drug-resistant strain likely will need therapy for up t 24 months and has only a 50% chance of being cured. Mortality rates for those with both MDR-TB and HIV infection have been very high, ranging from 75%-90%, with the time from diagnosis to death as little as four weeks. A high proportion of those with MDR-TB have been people with HIV (CDC. Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues. MMWR. 1990;39(RR-17):[pages inclusive].) Drug-resistant TB poses further problems because it may take weeks or months to diagnose. Diagnosis can occur only after treatment has begun, and clinicians must respond immediately by using other, perhaps less effective, therapies. A California study found that 15% of all reported TB cases during the first-quarter of 1991 were resistant to at least one anti-TB drug (Coulter, Steward, State of California, Department of Health Services, Berkeley. Personal communication, February and March 1993). A recent survey of TB cases in New York found that 33% of cases studied had strains of TB resistant to at least one anti-TB drug, and almost 20% were resistant to isoniazid (INH) and rifampin (RIF), the two most effective drugs available. Drug resistant TB is becoming more prevalent in many institutional settings, such as hospitals and correctional facilities. High rates are found among low-income immigrants, refugees and homeless people, groups for whom adherence to treatment is difficult to achieve. Lack of access to health care and environments in which they can easily take medications, as well as barriers of culture or language, lead many of these people to stop treatments once symptoms have disappeared. (Drug-Resistant TB. HIV Counselor Perspectives. 1993 April;3(2):3). Multidrug-Resistant Tuberculosis Has Become More Prevalent A newer and more dangerous type of multiple-drug resistance has developed in the AIDS era. Although the great majority of patients infected with multidrug-resistant Mycobacteria tuberculosis organisms have had advanced AIDS, these bacilli represent a threat to both HIV-positive and HIV-negative individuals in the future. Between 1990 and early 1992, seven outbreaks of multidrug- resistant tuberculosis were reported to the Centers for Disease Control and Prevention. All such cases occurred in hospitals or prisons in New York or Florida. More than 200 cases of multidrug- resistant tuberculosis have been documented; about 90 percent of the patients were infected with HIV, and many had advanced AIDS at the time of diagnosis. Nosocomial transmission of multidrug- resistant organisms has been demonstrated in these outbreaks. The major risk factors have been advanced AIDS and exposure to other AIDS patients with infectious multidrug-resistant tuberculosis in AIDS clinics or wards. Transmission to at least nine health care workers and prison guards has been documented; most of these individuals, including the five persons who died, were shown to be HIV positive. The mortality of multidrug-resistant tuberculosis has been exceedingly high, ranging from about 70 to 90 percent; most deaths occurred within four to 16 weeks of diagnosis, and the affected patients had wide-spread miliary tuberculosis. (Scientific American Medicine. 7 Infectious Disease, VIII Infections Due to Mycobacteria, p. 13, 14.) Management of Multidrug-Resistant Tuberculosis Poses Severe Problems All the organisms isolated from patients in the outbreaks of multidrug-resistant tuberculosis have been resistant to isoniazid, and nearly all have been resistant to rifampin. Many organisms have been resistant to all five first- and second-line drugs, and some have been resistant to seven drugs. For example, in one outbreak in which multidrug-resistant tuberculosis developed in 62 patients, 100 percent of the organisms were resistant to isoniazid, 97 percent to rifampin, 58 percent to ethambutol, 22 percent to ethionamide, three percent to cycloserine, and two percent to streptomycin. The management of multidrug-resistant tuberculosis is exceedingly difficult, and early diagnosis is critical. Once the diagnosis is suspected, the organisms can usually be identified without difficulty. To interrupt the transmission of multidrug- resistant tuberculosis, stringent isolation procedures are mandatory. Aggressive chemotherapy with a combination of drugs is essential. The choice of agents must depend on the results of the susceptibility testing, but until such results are available, the drugs most likely to be effective include pyrazinamide, streptomycin, ciprofloxacin, ofloxacin, cyclosierine, ethionamide, and ethambutol. The most effective drug regimens have not been established; the ultimate outcome may be influenced as much by host factors as by the type of chemotherapy that is used. The management of individuals exposed to multidrug-resistant tuberculosis is also difficult. Such individuals should be evaluated for the closeness of their contact with infected persons and their immune status. Individuals at high risk are candidates for chemoprophylaxis; possible regimens include pyrazinamide plus ethambutol in standard doses or pyrazinamide in standard doses plus ciprofloxacin (750 mg twice daily) or ofloxacine 400 mg twice daily). Multidrug-resistant tuberculosis still constitutes a small minority of all cases of tuberculosis. Most failures of antituberculosis chemotherapy stem from poor patient compliance rather than drug resistance. (Scientific American Medicine. 7 Infectious Disease, VIII Infections Due to Mycobacteria, p. 14.) [Editor's Note: Guidelines for tuberculosis management will be covered in more detail in the next issue of this newsletter.] MULTIDRUG-RESISTANT TUBERCULOSIS AND HIV INFECTION References -- 1992-93 Arranged Alphabetically by Author Abrutyn E. Multidrug-resistant nosocomial TB: newest facet of the HIV epidemic [editorial]. Hospital Practice (Office Edition), 1992 Sep 30, 27(9A):11, 15-6. Bader JM. France: nosocomial multidrug-resistant TB [news]. Lancet, 1992 Dec 19-26, 340(8834-8835):1533. Bakshi SS; Alvarez D; Hilfer CL; Sordillo EM; Grover R; Kairam R. Tuberculosis in human immunodeficiency virus-infected children. A family infection. American Journal of Diseases of Children, 1993 Mar, 147(3):320-4. Bayer R; Dubler NN; Landesman S. The dual epidemics of tuberculosis and AIDS: ethical and policy issues in screening and treatment. American Journal of Public Health, 1993 May, 83(5):649-54. Beck-Sague C; Dooley SW; Hutton MD; Otten J; Breeden A; Crawford JT; Pitchenik AE; Woodley C; Cauthen G; Jarvis WR. Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients. Jama, 1992 Sep 9, 268(10):1280-6. Bloom BR; Murray CJ. Tuberculosis: commentary on a reemergent killer [see comments]. Science, 1992 Aug 21, 257(5073):1055-64. Busillo CP; Lessnau KD; Sanjana V; Soumakis S; Davidson M; Mullen MP; Talavera W. Mltidrug resistant Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. Chest, 1992 Sep, 102(3):797-801. CDC advises on management of persons exposed to multiple-drug- resistant tuberculosis [news]. Clinical Pharmacy, 1992 Dec, 11(12):991, 994, 999. CDC issues guidelines for multidrug-resistant tuberculosis. American Family Physician, 1992 Oct, 46(4):1303-5. Centers for Disease Control. Transmission of multidrug- resistant tuberculosis among immunocompromised persons, correctional system--New York, 1991. Jama, 1992 Aug 19, 268(7):855-6. Chawla PK; Klapper PJ; Kamholz SL; Pollack AH; Heurich AE. Drug- resistant tuberculosis in an urban population including patients at risk for human immunodeficiency virus infection [see comments]. American Review of Respiratory Disease, 1992 Aug, 146(2):280-4. Collins FM. Tuberculosis: the return of an old enemy. Critical Reviews in Microbiology, 1993, 19(1):1-16. Cotte L; Fougerat F; Trepo C. Nosocomial transmission of multidrug-resistant tuberculosis between AIDS patients [letter]. Tubercle and Lung Disease, 1992 Dec, 73(6):397-8. Dooley SW; Jarvis WR; Martone WJ; Snider DE Jr. Multidrug-resistant tuberculosis [editorial; comment]. Annals of Internal Medicine, 1992 Aug 1, 117(3):257-9. Edlin BR; Tokars JI; Grieco MH; Crawford JT; Williams J; Sordillo EM; Ong KR; Kilburn JO; Dooley SW; Castro KG. An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. New England Journal of Medicine, 1992 Jun 4, 326(23):1514-21. Farley TA. AIDS and multidrug-resistant tuberculosis: an epidemic transforms an old disease. Journal of the Louisiana State Medical Society, 1992 Aug, 144(8):357-61. Fischl MA; Daikos GL; Uttamchandani RB; Poblete RB; Moreno JN; Reyes RR; Boota AM; Thompson LM; Cleary TJ; Oldham SA. Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. Annals of Internal Medicine, 1992 Aug 1, 117(3):184-90. Fischl MA; Uttamchandani RB; Daikos GL; Poblete RB; Moreno JN; Reyes RR; Boota AM; Thompson LM; Cleary TJ; Lai S. An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection [see comments]. Annals of Internal Medicine, 1992 Aug 1, 117(3):177-83. Frieden TR; Sterling T; Pablos-Mendez A; Kilburn JO; Cauthen GM; Dooley SW. The emergence of drug-resistant tuberculosis in New York City. New England Journal of Medicine, 1993 Feb 25, 328(8):521-6. Galai N; Graham N; Chaisson R; Nelson KE; Vlahov D; Lewis J. Multidrug-resistant tuberculosis [letter]. New England Journal of Medicine, 1992 Oct 15, 327(16):1172-3; discussion 1174. Githui W; Nunn P; Juma E; Karimi F; Brindle R; Kamunyi R; Gathua S; Gicheha C; Morris J; Omwega M. Cohort study of HIV-positive and HIV-negative tuberculosis, Nairobi, Kenya: comparison of bacteriological results. Tubercle and Lung Disease, 1992 Aug, 73(4):203-9. Grosset JH. Treatment of tuberculosis in HIV infection. Tubercle and Lung Disease, 1992 Dec, 73(6):378-83. Hopewell PC. Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management, and control of tuberculosis. Clinical Infectious Diseases, 1992 Sep, 15(3):540-7. Horn DL et al. Fatal hospital-acquired multidrug-resistant tuberculous pericarditis in two patients with AIDS [letter]. New England Journal of Medicine, 1992 Dec 17, 327(25):1816-7. Horn DL et al. RISE-resistant tuberculous meningitis in AIDS patient [letter]. Lancet, 1993 Jan 16, 341(8838):177-8. Israel HL. Drug-resistant tuberculosis in New York City [letter]. New England Journal of Medicine, 1993 Jul 8, 329(2):134-5. Khouri YF; Mastrucci MT; Hutto C; Mitchell CD; Scott GB. Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection. Pediatric Infectious Disease Journal, 1992 Nov, 11(11):950-5. Landesman SH. Commentary: tuberculosis in New York City--the consequences and lessons of failure. American Journal of Public Health, 1993 May, 83(5):766-8. Lerner BH. New York City's tuberculosis control efforts: the historical limitations of the "war on consumption". American Journal of Public Health, 1993 May, 83(5):758-66. Nolan CM. Failure of therapy for tuberculosis in human immunodeficiency virus infection. American Journal of the Medical Sciences, 1992 Sep, 304(3):168-73. Pozniak AL; MacLeod GA; Mahari M; Legg W; Weinberg J. The influence of HIV status on single and multiple drug reactions to antituberculous therapy in Africa. Aids, 1992 Aug, 6(8):809-14. Schurmann D. Bergmann F. Jautzke G. et al. Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases. Journal of Infection. 26(1):45-54, 1993 Jan. Selwyn PA; Sckell BM; Alcabes P; Friedland GH; Klein RS; Schoenbaum EE. High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy. Jama, 1992 Jul 22-29, 268(4):504-9. Small PM; Shafer RW; Hopewell PC; Singh SP; Murphy MJ; Desmond E; Sierra MF; Schoolnik GK. Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection [see comments]. New England Journal of Medicine, 1993 Apr 22, 328(16):1137-44. Tokars JI; Jarvis WR; Edlin BR; Dooley SW; Grieco MH; Gilligan ME; Schneider N; Montonez M; Williams J. Tuberculin skin testing of hospital employees during an outbreak of multidrug-resistant tuberculosis in human immunodeficiency virus (HIV)-infected patients [letter]. Infection Control and Hospital Epidemiology, 1992 Sep, 13(9):509-10. [Submitted by: Michael Howe (hivinfo@itsa.ucsf.edu) Fri, 1 Apr 1994 08:48:44 -0800] .