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Herd immunity and the HIV epidemic
PREVENTIVE
MEDICINE
20,
329-342 (191)
Herd Immunity
and the HIV Epidemic
WILLIAM T. O'CONNOR, M.D. Department of Family Practice Medicine, School of Medicine, University of California, Davis, California 95616 Background. Herd immunity describes the collective immunocompetence of a population and its ability to resist disease. The diseases of mycobacteria, salmonella, hepatitis A, cryptosporidia, syphilis, measles, influenza, and numerous others recently have been seen in epidemic proportions in the United States. An association between these superimposed secondary infections and the human immunodeiiciency virus (HIV) epidemic can be made since the HIV’s imposition on individual immunity has ramifications on a population level through a decline in herd immunity. Conclusion. Exploring these epidemic phenomena as consequential to a reduction in herd immunity can provide a unifying hypothesis to explain existing and predict future infectious disease epidemic dynamics. The benefits of acting upon these implications has advantages for both the HIV infected and the uninfected. o 191 Academic press, IUC.
INTRODUCTION
Herd immunity is considered to be the collective immunity of a given population or “herd” that imparts to that group a protection against destruction by epidemics. It is formally defined as a group immunity that confers a resistance or relative resistance to infectious disease because of the immunity of a large proportion of the members of that population. The immune status of a population as a whole is determined by the ratio of resistant to susceptible members and their distribution. Just as a human body with some defect in the cellular units that confer protection against disease suffers by becoming diseased, so, too, when a society’s individual components have immune defects, the entire society can be seen to suffer a morbid consequence. Population members with human immunodeficiency virus (HIV) infections and especially acquired immune deficiency syndrome (AIDS) lose immune competence, making them more likely to retain, be infectious for, and die from not only opportunistic infections but also a multitude of superimposed secondary infections. Consequently, they are more apt to function as sources of communicable disease outbreaks because they remain infectious for relatively longer periods of time, creating increased absolute numbers as well as serving as reservoirs and vectors for contagious organisms. Diseases that are prevented from transmission by competent immune systems become recurrently infectious in the HIV-infected. This recurrence of disease has been described for hepatitis B (l), herpes simplex (2), and varicella-zoster (3), putting the HIV-infected at increased risk of repeatedly serving as sources of r Address reprint requests to the author at The HIVE 956%.
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infectious diseasetransmissionsthat would otherwise have been suppressedin the presence of a competent immune system. The epidemiology of infectious diseaseleads one to conclude that the successful transmission, and, therefore, resultant acquisition, of diseaseis largely a function of exposure frequency. If a source for repeated exposures exists in any given environment, then persons sharing those environments are at higher risk of acquiring those diseasesdue to the increased concentrations of microorganisms. When a “herd” contains numerous individuals who lack immune competence and who produce higher concentrations of pathogenic organisms, the probability of successful transmissions occurring is also increased. When immune competence fails at this population or societal level, it can be interpreted as a deterioration of that population’s herd immunity. Coincident with the advent of the “AIDS Era,” the medical community has borne witness to an increase in the incidence and prevalence of numerous previously controlled infectious diseases. The relationship between these two simultaneous phenomenabears an associativeepidemiological significance that can be explained by a decline in the U.S. population’s herd immunity. TUBERCULOSIS
The human immunodeficiency virus has been causally linked to this decade’s well-documented tuberculosis (TB) epidemic in the United States, as well as globally (5-12). Since 1953,when uniform national reporting becameimplemented in the United States, the incidence of tuberculosis had been decreasing by approximately 6% per year (13). Even with the heavy influx of infected Southeast Asians as a result of the Vietnam War, the incidence of TB had decreasedsteadily by 5.9% annually from 1963to 1985.The first substantial increase, of 2.6% (14), was observed in 1986. In New York City, reported TB cases increased by 36% from 1984to 1986,the increase being causally related by the U.S. Public Health Service to HIV (15). Although this TB epidemic can appear to be solely attributable to AIDS patients with TB and the nearly lOO-foldgreater probability (over the general population) (16, 17) of an HIV-infected person acquiring the disease, it is important to note that the increased acquisition of TB is not limited to those afflicted with HIVrelated conditions. There is an almost commensuratepercentage of persons newly diagnosed with TB but without HIV infection. According to the Centers for Disease Control statistics, 53% of 58 males ages 25-44 years without AIDS but confirmed to have Mycobacterium tuberculosis were found to be HIV seropositive (18), leaving 47% to have diseaseindependent of HIV infections. Therefore, these TB acquisitions appear to be contributing almost equivalently to the statistical increase in incidence. Tuberculosis rates can be used as one determinant to indirectly quantify the damage to a population’s herd immunity, since its pathogenicity seems to be inversely related to the immunocompetenceof its hosts. Certain institutions with increased AIDS case rates already can be used to demonstrate HIV’s effect upon the population. During 1988, the estimate aggregate reported incidence of AIDS in the U ,S. population was 13.7/100,000,whereas
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in state and federal correctional systems it was 75/100,000(19). One review of AIDS casesamong inmates in selected New York correctional facilities found TB in 6.9% of 319 persons with AIDS (20). It comes as no surprise that the incidence of TB in prisons increased 400% in the period 19761986 (21). In one Urbana, Illinois, hospital, 13health care workers were believed to have been infected with M. tuberculosis from a single AIDS patient (22). These HIV-mediated TB epidemics translate as especially threatening in the context of the total population when one considers routine transmission by the aerosol route, the increased HIV-related susceptibility, the failure of antimicrobial therapy to eliminate disease in HIV carriers even when treating susceptible strains (23), and the 6% rise in drug-resistant strains of tuberculosis since the mid-1970s (24). ATYPICAL MYCOBACTERIA
Atypical or nontuberculous mycobacteria have recently received increased scrutiny due to their significance in relation to the AIDS epidemic. Up to 53% of AIDS patients on autopsy have nontuberculous bacterial infections categorized as Mycobacterium avium complex (MAC) (25). In deference to the belief that these infections are only opportunistic, healthy young people with no evidence of impaired cellular immunity can and do acquire this disease (26); and, in contrast to those who would look upon these organisms’ transmissions as largely environmental, one review (27) cites reports that suggestperson-to-person transmissions, intrafamilial spread, and acquisition by health care workers. One outbreak in 1987 resulted in Mycobacterium chelonae infecting 17 persons as a result of contaminated ENT instruments (28). Culture analysis has shown that isolates of atypical mycobacteria in sputum of patients with associated pulmonary disease usually were different from those of the patient’s environmental strains (29), leading one to conclude that the organisms responsible for their diseasewere less likely to have been environmental in origin, leaving person-to-person transmissions a more likely source of infection. Serotype analysis has shown that certain serotypes of M. intracellulare were associated with the production of disease and these differed from the serotypes found in that environment, indicating that certain serotypes had higher pathogenicity and the human body probably served as a selective media (30). The relationship between MAC and AIDS may explain the increasing prevalence of MAC in the United States (31) due to the population’s increasing immune incompetence. Particularly disconcerting is that nontuberculous disease is being seen in increased incidence in areas considered previously to have relatively low isolation rates (Philadelphia) and among elderly females without predisposing conditions (32). The clinical observation that these infections are frequently fatal despite multiple drug regimens even in persons without underlying predisposing conditions (33) is significant; and, in those with severe immune deficits, therapy is rarely successful (34). Nontuberculous mycobacterium remain viable for long periods in the environment (35), are assumedto be spread by the air-borne route, and have been shown recently to have contaminated the water supplies of hos-
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pitals where AIDS patients are in high prevalence (36), indicating a potential for increasing nosocomial spread. SALMONELLA
Salmonellahas been recently seen in epidemic proportions in the United States (37-39). Although salmonellaoutbreaks have been attributed to Grade A eggs(40) and pasteurized milk (41), New England and the Mid-Atlantic States during the period 19761988 saw approximately an eight- to ninefold increased isolation rate for Salmonella enteritidis (42). The incidence of typhoid fever (Salmonella typhi) in the United States increased in 1989to a cumulative case rate 25% greater than the median levels for 1984-1988(43). Recent salmonella outbreaks in New York City, an area endemic for HIV, such as those at Mt. Vernon Hospital (involving 15 patients, 2 nurses, and a physician) and at Coler Memorial Hospital (that claimed 175 victims and 3 lives) (44), and a typhoid fever outbreak in the San Francisco area (45) appear to bear a geographical and associative relationship to the HIV epidemic since AIDS patients are 20 times more likely than the general population to be Salmonella carriers and most have persistent infections or recurrences despite appropriate antimicrobial therapy (46). HEPATITIS A
In the United States from 1983 to 1989 there has been a 58% increase in the incidence of reported hepatitis A infections (47,48). Were this country undergoing a major deterioration in the standard of living, sanitation, or Public Health Department activity, alternative explanations could be strongly supported; however, the increased prevalence of persons with deficient immune systemsthat allow the hepatitis A infections to be prolonged or inefficiently neutralized by protective antibody is an especially intriguing explanation since these previously unrecognized risk factors have an equally common association in that they are both likely to be associated with HIV infection. Prior to the advent of the HIV epidemic, hepatitis A had only been associated with crowding, poor personal hygiene, improper sanitation, and (less commonly) contamination of food or water and the recognized risk factors of intimate contact with infected persons, day care, and travel to underdeveloped countries. Most recently, an outbreak has been identified among at least 80 students and staff at the University of Southern California in Los Angeles (49), which is not a characteristic environment to sustain an epidemic requiring the previously cited conditions if they are considered prerequisites. A valid factor contributing to the most prolonged hepatitis A outbreak in the history of the Centers for Disease Control is probably that the source case(s) had immunosuppressioninduced by human immunodeflciency virus infection. Two of the pantry worker source casesin a study of 103 casesof hepatitis A in a Florida restaurant (50) were described as male homosexuals,promiscuous, and practitioners of anal intercourse. One had engagedin anal intercourse three to four times per month and shortly afterward acquired hepatitis B. Although all of these activities were recognized risk factors for HIV, the workers were unfortunately not
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tested for HIV; however, according to the author of the study, they “could reasonably be assumedto have been infected by HIV” (51). A large outbreak in Texas at a salad-bar restaurant (52) and two other foodborne outbreaks in Alaska were traced to homosexual male source cases (53). In the past 10 years, nearly 50% of source casesassociatedwith food-borne hepatitis A outbreaks in California have been homosexual men (54). Intravenous drug users have been only recently identified as sources of type A hepatitis in New York state and northern California (55). This association is strengthened by a geographical correlation since California and New York are the states of highest AIDS incidence. Previously it had been held that hepatitis A outbreaks were not sustained by blood-borne routes due to the short duration of the viremia. However, in persons with immunodeticiencies, it is reasonable to assume that the viremia would be prolonged enough to sustain such outbreaks and, thus, provide an explanation for this new association. CRYPTOSPORIDIOSIS
The immunity of the U.S. “herd” had been sufficient in the past to keep cryptosporidiosis at an incidence so low that it was not observed by the medical community. Prior to the advent of the AIDS epidemic it went unreported as a human pathogen in the United Statesuntil 1976(56). Only recently has this enteric pathogen been identified as one of the more common causes of intractable diarrhea among AIDS victims-being seenin as much as 15%(57) to 20% (58) of those with chronic diarrhea, but, retrospectively, can be assumed to have been contributing to the late 1970sphenomenon known as “Gay Bowel Syndrome.” In the period 1976-1981,the first seven cases of human cryptosporidiosis were reported and in five of the seven cases the patients were immunocompromised (59). Since then, it has been linked to day care centers in San Francisco (60) and elsewhere (61,62) and has infected nearly 13,000people in Western Georgia after it contaminated a water supply (63). It is highly infectious (64), can kill children (65), and can be transmitted when the spores dry out and carried through the air (66); and person-to-person spread has been documented (67). It appears that the emergence of this organism as a human pathogen in the United States has been relatively recent. Its association with the immunocompromised may have allowed it to attain sufficient concentrations in human hosts to increase its prevalence. SYPHILIS
Decreasing syphilis rates from the 1940s to the 1950swere largely due to a combination of serologic testing, public health measures, and the availability of a cure. With the often described successesin educational efforts to reduce sexual behaviors that put individuals at high risk for sexually transmitted diseases, especially HIV, one would assume that syphilis rates should still be declining; however, the opposite is true. The previous downward trends were reversed in 1987when the United States experienced at least a 25% increase over the previous year (68). Geographically, this increase has predominately occurred in areas of high HIV prevalence. Eighty-three percent of the national increase and 57% of all
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casesoccurred in New York City, California, and Florida (69). Between 1981and 1989, the incidence of primary and secondary syphilis in the United States increased 34%, from 13.7 to 18.4 cases per 100,000 persons (70), with a 9.7% increase in 1989,representing a 52% increase over the median incidence for 19841988(71). Numerous explanations have been advanced, including sexual promiscuity related to drug use, use of spectinomycin (which does not cure incubating syphilis), and decreased public health resources (72). Neglected in these explanations are the influences consequent to herd immunity decline due to the prevalence of HIV which allows those with concomitant HIV and syphilis infections (who continue to practice sexual behaviors) to transmit syphilis more efficiently. High therapeutic failure rates occur amongpatients infected with both HIV and syphilis even when recommendedlevels of antibiotics are administered (73), leading to the conclusion that spirochetes sequesteredin the central nervous system and elsewhere in the immunoincompetent can serve as sources for reinfection of the host and infection of his/her sexual contacts that would have otherwise been prevented in the presence of immunocompetence. Others have recognized an association between genital ulcer disease and HIV (74, 75). On the basis of this association, some would conclude that behavioral considerations and/or the presence of blood contact with the syphilitic ulcer predisposed the acquisition of HIV. An equally plausible explanation is that the disease causing the ulcer was present largely due to the HIV-induced loss of immunity in either the transmitter or the recipient of disease. Attempts to determine which condition preceded the other so that a cause-effect relationship can be substantiatedwould be difficult to elaborate, but the association cannot be denied. MEASLES
Measles vaccination programs were effective in steadily and markedly reducing the occurrence of this diseaseduring the years 1962-1983.However, concurrent with the AIDS Era, the period 1983 thorugh the present has seen an overall increase in measlesincidence, continuing with substantial increases in 1989(76). During 1989,a 430% increase in caseswas reported over the same period in 1988 (77). Consistent with other recent epidemics, measlesoutbreaks have been observed in areas with relatively high HIV seroprevalence, such as Los Angeles (78) and Dade County, Florida (79)) indicating (in the absenceof a more virulent organism) a loss in herd immunity to measles demographically associated with relatively high HIV prevalence. The larger part of this epidemic occurrence cannot be explained on the basis of an increasingfailure to have children immunized. In 1988,68.9%of reported cases occurred among school-age children who had been previously vaccinated and most vaccine failures occurred in persons 12-19 years of age (80) who earlier were believed to be sufficiently protected. HIV-infected persons with measlesdo not necessarily demonstrate the typical, diagnostic rash (81). Therefore, these carriers can serve as more efficient sources of outbreaks for longer periods becausethe absenceof typical clinical symptoms
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precludes diagnosis, thereby delaying or preventing initiation of treatment, outbreak control measures, or appropriate isolation procedures (82). It is likely that a substantial number of HIV-infected individuals transmit the measles virus due to a failure of vaccine-induced humoral immunity. This phenomenon has been described in a previously immunized 16year-old HIV carrier who had been immunized with live-attenuated measlesvaccine at 15 months and again at 9 years of age yet still developed serologically confirmed measles (83). In deference to claims that a primary vaccine performance failure may be responsible (84), it is reasonable to assume that a stable rate of individual vaccine performance failures had been present throughout the history of measles immunization programs; yet a failure had not been observed because the prevalence of the measlesvirus was kept low enough by national vaccine performance (induced herd immunity) to prevent the percentage of poor vaccine responders from being epidemiologically observed. However, when higher numbers of measles carriers exist in the population, the statistical probability of an inadequately immunized individual (either from a primary vaccine failure or a waning of vaccine-induced immunity) being exposed, infected, and becoming infectious correspondingly increases. An increase in infections among previously immunized persons would not have been observed if the herd immunity had remained constant or increased. By exclusion, this event could only have occurred in the presence of a reduction in herd immunity. INFLUENZA
A reduction in herd immunity also serves to explain the currently and continuously increasing influenza activity (85). The mortality from pneumonia and influenza reported by vital records offices in 121 U.S. cities recorded from 1979 through 1989has shown a progressive increase from approximately 3.5 to 5.5% (86). Data from the Centers for Disease Control have shown that during the 1980s the number and percentage of deaths attributable to pneumonia and influenza among persons ages 25-44 years more than doubled in cities with high AIDS incidence (87). Nationally, the number of deaths from influenza and pneumonia during 1988was higher than that for the preceding 4 years. The association with AIDS and influenza is significant enough for some authors to advocate annual immunization of the HIV-infected’s household contacts (88). Again, it has been shown that more than half of persons with AIDS or ARC (AIDS-related complex) do not produce antibodies considered to be protective in response to four different influenza vaccines (89). It can be assumed, then, that once infected by the initial wild-type influenza virus, the HIV-afflicted host will retain and be infectious for this organism for significantly longer periods than their immunocompetent counterparts. DISCUSSION
When members of a population with faulty immune systems are increasingly distributed throughout a population, the incidence and prevalence of other communicable diseases increase as herd immunity declines. No single factor better serves to explain the multiple epidemic increases being seen in the United States
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since the advent of the AIDS Era than the effect of HIV itself. If the abovedescribed epidemics were the only infectious diseaseconsequencesto be considered, the population damage occasioned by the destruction of herd immunity might be limited to a degree commensuratewith society’s ability to managethese select organisms. However, these epidemics may be serving as currently quantifiable heralds for the human population’s profound future interaction with all infectious diseasesif preemptive measuresare not employed. Because immunocompetence exists more as a spectrum of varying degree rather than as a qualitative distinction and because susceptibility to morbidity depends upon variable genetic, environmental, and other pathogenic influences, that large segmentsof the population have preexisting disease or are relatively immunosuppressed for a wide variety of reasons exclusive of HIV infections cannot be ignored. Especially at risk in an era of declining herd immunity are the young, pregnant women, the elderly, and those with chronic disease. The propensity for the HIV-infected to influence the transmission of diseasefor even those pathogens generally accepted to be exclusively opportunistic has been shown in relation to Pneumocystis carinii pneumonia. In a Texas cancer center, a nearly dose-related infection acquisition response in cancer patients that increasedwith the number of AIDS admissionsand declined equivalently when the number of AIDS registrations fell was observed (90). Beyond direct diseasetransmissions there are other less obvious ramifications to be considered as herd immunity is compromised. A substantial number of currently used serologic screensand diagnostic modalities rely upon humoral and cell-mediated immunocompetencefor proper function at both the individual and the population level. As a population’s immunocompetenceis lost, modem medicine’s ability to cheaply and efficiently screen for the presence or absence of disease is jeopardized. In the case of tuberculosis, anergy to skin testing is seen in up to 29% of AIDS patients (91) and the absenceof cavitations on chest X-ray cannot be relied upon since this is a cell-mediated response and distinctly uncommon in AIDS (92). Hicks et al. (93) have described this phenomenon wherein HIV-infected patients’ faulty immune systems fail to produce sufficient antibody against treponemal antigens to allow seropositivity to be recognized on the standard tests (VDRL and FTA-ABS) that rely upon these antibodies for proper function. Societies that have come to rely upon these types of sophisticated medical technologies can expect a substantial quantity of disease to go undetected for longer periods, giving rise to both prolonged carrier states and increased frequencies of infectious transmissions. Also, the ability to induce and benefit from the herd immunity that has served as a basis for broad-basedvaccination strategies(94) will be significantly impaired as a consequence of the HIV epidemic’s influence. The effort to increase herd immunity has long been evoked as a justification for mandatory immunization programs that require children to be vaccinated against diseasesbefore allowing them to enter schools. Acting upon that logic was demonstrably successful. As with measles,diseaseresurgence has also been observed with regard to mumps.
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During the period 1985-1987,the annual incidence rate rose almost fivefold (95), and 1989 saw a 15% increase over the previous year (96). The human population can expect a future increase not only in the numbers of sameserotype epidemics but also in the number of serologically different epidemics. This can be predicted because the bulk of human infectious diseases do not reproduce in the environment. They require human hosts in which to undergo the successiveand successful mutations that allow antigenic drift and shift to occur. One limiting factor in the rate of antigenic shift or drift is the immunity generated by individuals in the population that eradicates the organisms from the host prior to their production of new immunologically distinct strains. These strains most probably originate in hosts, and it is logical to assume that they originate in humans who are infected with the progenitor strain. When a declining herd immunity allows pathogens to thrive for prolonged periods of time and the number of human hosts to increase, the statistical probability that new serotypes will develop can only be increased. HIV infections in the hosts provide precisely that environment by preventing an appropriate immune response from eradicating the organisms before they undergo sufficient mutational events that allow the creation of novel, serologically distinct strains. It is not unreasonable to consider that the use of live-attenuated viral vaccines in the HIV-infected might be allowing the production of subclinical infections with reversion mutations that are as transmissible and pathogenic as the original strains. The HIV itself appears to capitalize upon its induction of immunoincompetence combined with a prolonged duration of infection and propensity for mutagenicity to produce variant surface morphologies that allow increased infectivity and the creation of successiveHIV serotypes that require specific immune responseseach more progressively difficult to generate in order to effect successful antibody neutralization. This prolonged period of virus presence that predisposes an increased opportunity for viral mutagenicity and variant clone creation has been previously described in relation to a continuous varicella-zoster infection in a child with AIDS who developed an acyclovir resistance during the course of her treatment (97), an acyclovir-resistant herpes simplex in AIDS patients (98), and a ganciclovirresistant cytomegalovirus in AIDS patients (99). These findings raise the specter of yet another threat (100) to the ability of “the herd” to avoid associated disease and are consistent with the recently increasing frequency and rapid development of antimicrobial resistance in both viruses (101) and bacteria (102, 103). CONCLUSION
Out of necessity, the HIV epidemic causes us to reevaluate the relationships that individuals have with their society and how society relates to its members in the context of infectious disease. The belief that our society had evolved beyond the catastrophic consequencesof infectious diseaseshas had to be abandoned in light of the entry of the human immunodeficiency virus into the grand equation of life and death. At the very least, the epidemiological findings of temporal, risk group, and geographical associations make the relationship between the HIV
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epidemic and superimposed secondary epidemics worthy of heightened epidemiological exploration and intervention. These considerations may require a reexamination of the function and designation of institutions, facilities, equipment, procedures, and even laws that our society designed in a past era of heightened herd immunity. Vaccination recommendations (such as BCG inoculation, repetitive measles boosters, influenza vaccine) must evolve to bolster the immunity in health care workers, prisoners, prison employees, or any others routinely exposed to populations with high HIV carrier rates. Since HIV will undoubtedly influence the epidemiology of communicable diseases (especially as they relate to subsequent environmental transmissions of enteric pathogens) public health departments should consider including preferential investigative HIV testing of source casesin local infectious diseaseoutbreaks and those persons in the food service industry implicated in outbreaks of any food-borne pathogen. In addition, frequent laboratory and/or clinical monitoring of HIV-infected health care, child care, or food service employees should be implemented so that, if infected with a communicable superimposedsecondary infection (whether specifically symptomatic or not), they can be removed from that environment until it can be demonstrated that they no longer pose a risk for contagion. Ultimately, a strategy of confidential HIV testing, identification, and monitoring of the infected (whenever an individual’s contact can be seen to put other persons at risk) would efficiently allow a focused surveillance for the HIV-related superimposed secondary infections and would be cdrrtistent with a public health policy that places a priority on disease prevention. It must realize that HIV carriers, too, are at especially higher risk of acquiring superimposeddiseasewhen they are in contact with any population experiencing a reduction in herd immunity. Without question, the HIV carriers would benefit by limiting their exposure to pathogens as well as by being afforded the opportunity for early diagnosis and treatment (particularly those unaware that they are infected with superimposed secondary infections). Most certainly, the HIV-uninfected majority of society would benefit since the transmission of technologically preventable diseasewould be significantly reduced. REFERENCES 1. Vento S, Di Petri G, et al. Reactivation of hepatitis B in AIDS. Lancer 1989; 2:109-110. 2. Lynch JP. When opportunistic viruses infiltrate the lung. .I Respir Dis 1989; 10~25-30. 3. Reuler JB, Chang MK. Herpes zoster: Epidemiology, clinical features, and management. Sourh Med J 1984; 77(9): 1149-1156. 4. Tuberculosis and acquired immunodeficiency syndrome-New York City. MMWR 1987; 36(48):785-795. 5. Harries AD. Tuberculosis and human immunodeliciency virus infection in developing countries.
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8. Garcia ML, Valdespino JL, Salcedo A. et al. AIDS and tuberculosis. Encounter between two epidemics in a Latin American country. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1, Th.B.492244. 9. Maxwell M, Legg W, Houston S. Association of tuberculosis and HIV infection in Zimbabwe. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1, Th.B.494:245. 10. Kibuga DK, Gathua S. A study of HIV infection in association with tuberculosis as seen in infectious diseases hospital Nairobi. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1, Th.B.489:244. 11. Romo J, Salido F, Jessurum J. Tuberculosis and AIDS in a Mexican Hospital. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1, Th.B.491:244. 12. Santos R, Cruz A, Ribeiro T, et al. HIV Seroprevalence in tuberculosis patients in Bahia, Brazil. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1, Th.B.495245. 13. Centers for Disease Control. Use of BCG vaccines in the control of tuberculosis. MMWR 1988; 37:663-664, 669675. 14. Centers for Disease Control. Tuberculosis, final data-United States, 1986. MMWR 1988; 36817-819. 15. Tuberculosis and acquired immunodeficiency syndrome-New York City. MMWR 1987; 36(48):785-795. 16. Rieder HL, Cauthen GM, et al. Arch Intern hfed 1989; 149(6):1268-1273. 17. Tuberculosis and AIDS--Connecticut. MMWR 1985; 34:373-375. 18. Centers for Disease Control. Tuberculosis and acquired immunodeticiency syndrome-New York City. MMWR 1987; 36:(48):785-795. 19. Centers for Disease Control. Prevention and control of tuberculosis in correctional institutions: Recommendations of the Advisory Committee for the Elimination of Tuberculosis. MMWR 1989; 38(18):313-319. 20. Braun MM, Truman BI, Morse DL, Maguire B, Broaddus R. Tuberculosis and the acquired immunodeticiency syndrome in prisoners (Letter). JAMA 1987; 257:1471-1472. 21. Snider DE, Hutton MD. Tuberculosis in correctional institutions. JAMA 1989; 261(3):436-437. 22. Vance B. Urbana TB epidemic linked to AIDS patients. Peoria Journal Star, 7/16/87, Al. 23. Davis I, Acosta A, Lee S. Susceptible M. tuberculosis refractory to standard therapy with progression to central nervous system involvement. Abstracts: Sixth International Conference on AIDS, 1990, Vol. 1; Th.B.499:246. 24. Iseman MD. Drug-resistant tuberculosis-New threats from an old disease. Postgrad Med 1989; 86(2):109-l 14. 25. Hawkins CC, Gold JMW, Whimbey E, et al. Mycobncterium avium complex infections in patients with acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:184-188. 26. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119107-159. 27. Ibid., p. 126. 28. Lowry PW, Jarvis WR, Oberle AD, et al. Mycobacterium chelonae causing otitis media in an ear-nose-and-throat practice. N Engl J Med 1988; 319978-982. 29. Tsukamura M, Mizuno S, el al. A comparative study of mycobacteria from patients’ room dusts and from sputa of tuberculous patients: Source of pathogenic mycobacteria occurring in the sputa of tuberculous patients as causal isolates. Jpn J Microbial 1974; 18:271. 30. Ibid. 31. O’Brien RJ, Geiter LJ, Snider DE Jr. The epidemiology of nontuberculous mycobacterial diseases in the United States; results from a national survey,. Am Rev Respir Dis 1987; 135:10071014. 32. Prince DS, Peterson DD, Steiner RM, et al. Infection with Mycobqcterium ovium complex in patients without predisposing conditions. N Engl J Med 1989; 32L863-868. 33. Ibid., p. 867. 34. Lynch JP. Managing pulmonary infiltrates in immunocompromised patients. J Respir L&s 1988; 9(11):11-28. 35. Wolinsky, op. cit., p. 127.
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36. Stine TM, Harris AA, et al. A pseudoepidemic due to atypical mycobacteria in a hospital water supply. JAMA 1987; 258(6):809-811. 37. Ryan CA, Nickels MK, et al. Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk. JAMA 1987; 258(22):3269-3274. 38. St. Louis ME, Morse DL, Potter ME, et al. The emergence of grade A eggs as a major source of Salmonella enteritidis infections. JAMA 1988; 259:2103-2107. 39. Centers for Disease Control. Increasing Rate of Salmonella enteritidis infections in the northeastern United States. MMWR 1987; 36(1):1&11. 40. St. Louis, op. cit., p. 2103. 41. Ryan, op. cit., p. 3269. 42. Centers for Disease Control. Update: Salmonella enteritidis infections and grade A shell eggsUnited States, 1989. MMWR 1989; 38(51, 52):877-880. 43. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 44. Editor. Third patient dies of salmonella poisoning. American Medical News, September 4, 1987:63. 45. Bodovitz K. East Bay officials seek source of typhoid cases. San Francisco Chronicle, August 26, 1988. 46. Laurence J. Gastrointestinal infections in AIDS patients. Infect Med 1986; October:318-326. 47. Centers for Disease Control. Summary-Cases of Notifiable Diseases, United States. MMWR 1990; 38(51, 52):891. 48. Data supplied by Craig N. Shapiro, M.D., Medical Epidemiologist, Public Health Service, Hepatitis Branch Div. of Viral and Rickettsial Diseases, Centers for Disease Control, Atlanta, as reported in San Francisco Chronicle, 4115190. 49. Los Angeles Daily News, Hepatitis A Outbreak in Los Angeles, 12/28/1989, quoting Donnell Ewert of LA County Health Department. 50. Lowry PW, Levine R, et al. Hepatitis A outbreak on a floating restaurant in Florida, 1986. Am J Epidemiol 1989; 129(1):155-164. 51. Lowry PW, Personal communication, November 21, 1989. 52. Centers for Disease Control. Food-borne hepatitis A-Oklahoma, Texas. MMWR 1983; 32:652659. 53. Kosatsky T, Middaugh JP. Linked outbreaks of hepatitis A in homosexual men and in food service patrons and employees. West J Med 1986; 144~307-310. 54. Lowry PW, Levine R, et al. Hepatitis A outbreak on a floating restaurant in Florida, 1986. Am J Epidemiol 1989; 129(1):163. (quoting personal conversation with Dr. R. Roberto, CA Department of Health Serv., 1987) 55. Hepatitis A among drug abusers. MMWR 1988; 37:297-300, 305. 56. Nime FA, Burek JD, Page DL, et al. Acute enterocolitis in a human being infected with the protozoan Cryptosporidium. Gastroenterology 1976; 70~592-598. 57. Smith PD, Lane HC, Gill VJ, et al. Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Ann Zntern Med 1988; 108:328-333. 58. Nelson JA, Reynolds-Kohler C, Margaretten W, et al. Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms. Lancet 1988; 1:259-262. 59. Soave R, Armstrong D. Cryptosporidium and cryptosporidiosis. Rev Znfect Dis 1986; 8(6):10121023. 60. Infectious Disease Section California State Department of Health Services. Cryotosporidiosis: A newly recognized cause of diarrheal illness in day care centers. California Morbidity Weekly Report 1984; 41, October 19:l. 61. Alpert G, et al. Outbreak of cryptosporidiosis in a day care center. Pediatrics 1986; 77:1X2-157. 62. Gallaher M. Cryptosporidiosis outbreak linked to day-care center. Am J Public Health 1988; 7939-42. 63. Hayes EB, Matte TD, O’Brien TR, et al. Large community outbreak of cryptosporidiosis due to contamination of a faltered public water supply. N Engl J Med 1989; 328~1372-1376. 64. Soave, op. cit., p. 1015. 65. Peck P. Animal rights: Terrorists strike medicine. Physician’s Management 1989; June:49-68.
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66. Ibid. 67. Koch KL, Phillips DJ, Aber RC. Cryptosporidiosis in hospital personnel; evidence for personto-person transmission. Ann Intern Med 1985; 102:593-5%. 68. Centers for Disease Control. Syphilis and congenital syphilis-United States 1985-1988.MMWR 1988; 37486. 69. Centers for Disease Control. Continuing increase in infectious syphilis-United States. JAMA 1988; 259(7):975-977. 70. Rolfs RT, Nakashima AK. Epidemiology of primary and secondary syphilis in the United States, 1981through 1989. JAMA 1990; X4(11):1432. 71. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 72. Centers for Disease Control. Continuing increase in infectious syphilis-United States. JAMA 1988; 259(7):975-977. 73. McGuire R. Neurosyphilis: Menacing AIDS companion. Medical Tribune 1989;January 193-18. 74. Simonsen JN, Cameron DW, Gakinya MN, ef al. Human immunodeficiency virus infection among men with sexually transmitted disease: Experience from a center in Africa. N Engl J Med 1988; 319:274. 75. Stamm WE, Handslield HH, Rompalo AM, ei al. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA 1988; 260:1429. 76. Centers for Disease Control. Measles-United States, 1988. MMWR 1989;38(35):601~5. 77. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 78. Centers for Disease Control. Measles-Los Angeles County, California, 1988. MMWR 1989; 38(4):49-57. 79. Centers for Disease Control. Measles-Dade County Florida. MMWR 1987; 3ti45-48. 80. Ibid., p. 603. 81. Krasinski K, Holzman RS, Lacouture R, et al. Nosocomial measles: Are current vaccination guidelines for staff adequate? (Abstract). In: Program and Abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4-7, 1987. Described in: CDC, Measles in HIV-Infected Children, United States. MMWR 1988; 37(11, 12) (Obtained from JAMA) Leads from MMWR 1988; 259(16):2352-2357. 82. Enders JF, McCarthy K, Mitus A, Cheatham WJ. Isolation of measles virus at autopsy in cases of giant-cell pneumonia without rash. N Engl. J Med 1959; 261:875-881. 83. Centers for Disease Control. Measles in HIV-infected children, United States. MMWR 1988; 37(11, 12) (Obtained from JAMA) Leads from MMWR 1988; 259(16):2352-2357. 84. Markowitz LE, Preblud SR, Fine PEM, Orenstein WA. Duration of live measles vaccine-induced immunity. Pediutr Infect Dis J, in press. From: CDC, Measles-United States, First 26 Weeks, 1989. MMWR 1989; 38:863-872. 85. Centers for Disease Control. Influenza Activity-United States, 1989.MMWR 1989; 3k863-872. 86. Tipple MA, Kendal AP. Influenza epidemiology: Lessons from recent outbreaks. J Respir Dis Suppl. Influenza in the 1990’s: Use of Antiviral Agents in Prophylaxis and Treatment 1989; December:Sll. 87. Centers for Disease Control. Increase in pneumonia mortality in young adults and the HIV epidemic in New York City, United States. MMWR 1988; 32593. 88. Nelson KE. Annual influenza vaccination indicated for HIV-infected patients. Medical Aspects of Human Sexuality 1989; December:l. 89. Nelson KE, Clements ML, Miotti P, et al. The influence of HIV infection on antibody responses to influenza vaccines. Ann Intern Med 1988; 109:383. 90. Haron E, Bodey GP, Luna MA, et al. Has the incidence of Pneumocystis carinii pneumonia in cancer patients increased with the AIDS epidemic? Lancer 1988; 2904-905. 91. Mann J, Snider DE, Francis H, et al. Association between HTLV-III/LAV infection and tuberculosis in Zaire. JAMA 1986; 256(3):346. 92. Anon. TB making a comeback as AIDS-related pathogen. Med World News 1986; July 28:61. (Quoting Dr. Philip Hopewell, University of California, San Francisco)
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93. Hicks CB, Benson PM, Lupton GP, et al. Seronegative secondary syphilis in a patient infected with the human inununodeficiency virus (HIV) with Kaposi sarcoma. Ann Zntern Med 1987; lOT492-495. 94. Centers for Disease Control. Prevention and control of influenza. MMWR 1988; 37:361-364, 369-373. 95. Centers for Disease Control. Mumps prevention. MMWR 1989; 38(22):388-t00. %. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 97. Pahwa S, Biron K, Lim W, et al. Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA 1988; 260(19):2879-2882. 98. Erlich KS, Mills JM, Chatis P, Mertz GJ, et al. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320(5):293-2%. 99. Erice A, Chou S, Biron KK, Stanat SC, et nl. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N Engl J Med 1989; 32q5):289-293. 100. Zoler ML. Hospital infections got tougher. Medical World News 1990; September:12-13. 101. Norris SA, Kessler HA, Fife KH. Severe, progressive herpetic whitlow caused by acyclovirresistant virus in a patient with AIDS. J Infect Dis 1988; 157:209-210. 102. Handwerger S. Bacterial resistance to antibiotics seen increasing. Mod Med 1989; February(57):37. 103. Schwartz SK, Zenilman JM, et al. National surveillance of antimicrobial resistance in Neisseria gonorrhoeae. JAMA 1990; X4(11):1413-1417. Received June 15, 1990 Revised September 28, 1990 Accepted October 9, 1990
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Herd Immunity
and the HIV Epidemic
WILLIAM T. O'CONNOR, M.D. Department of Family Practice Medicine, School of Medicine, University of California, Davis, California 95616 Background. Herd immunity describes the collective immunocompetence of a population and its ability to resist disease. The diseases of mycobacteria, salmonella, hepatitis A, cryptosporidia, syphilis, measles, influenza, and numerous others recently have been seen in epidemic proportions in the United States. An association between these superimposed secondary infections and the human immunodeiiciency virus (HIV) epidemic can be made since the HIV’s imposition on individual immunity has ramifications on a population level through a decline in herd immunity. Conclusion. Exploring these epidemic phenomena as consequential to a reduction in herd immunity can provide a unifying hypothesis to explain existing and predict future infectious disease epidemic dynamics. The benefits of acting upon these implications has advantages for both the HIV infected and the uninfected. o 191 Academic press, IUC.
INTRODUCTION
Herd immunity is considered to be the collective immunity of a given population or “herd” that imparts to that group a protection against destruction by epidemics. It is formally defined as a group immunity that confers a resistance or relative resistance to infectious disease because of the immunity of a large proportion of the members of that population. The immune status of a population as a whole is determined by the ratio of resistant to susceptible members and their distribution. Just as a human body with some defect in the cellular units that confer protection against disease suffers by becoming diseased, so, too, when a society’s individual components have immune defects, the entire society can be seen to suffer a morbid consequence. Population members with human immunodeficiency virus (HIV) infections and especially acquired immune deficiency syndrome (AIDS) lose immune competence, making them more likely to retain, be infectious for, and die from not only opportunistic infections but also a multitude of superimposed secondary infections. Consequently, they are more apt to function as sources of communicable disease outbreaks because they remain infectious for relatively longer periods of time, creating increased absolute numbers as well as serving as reservoirs and vectors for contagious organisms. Diseases that are prevented from transmission by competent immune systems become recurrently infectious in the HIV-infected. This recurrence of disease has been described for hepatitis B (l), herpes simplex (2), and varicella-zoster (3), putting the HIV-infected at increased risk of repeatedly serving as sources of r Address reprint requests to the author at The HIVE 956%.
Foundation,
P.O. Box 808, Vacaville,
CA
329 0091-7435/91 53.00 Copyright 0 1991 by Academic Press. Inc. All rights of reproduction in my form reserved.
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infectious diseasetransmissionsthat would otherwise have been suppressedin the presence of a competent immune system. The epidemiology of infectious diseaseleads one to conclude that the successful transmission, and, therefore, resultant acquisition, of diseaseis largely a function of exposure frequency. If a source for repeated exposures exists in any given environment, then persons sharing those environments are at higher risk of acquiring those diseasesdue to the increased concentrations of microorganisms. When a “herd” contains numerous individuals who lack immune competence and who produce higher concentrations of pathogenic organisms, the probability of successful transmissions occurring is also increased. When immune competence fails at this population or societal level, it can be interpreted as a deterioration of that population’s herd immunity. Coincident with the advent of the “AIDS Era,” the medical community has borne witness to an increase in the incidence and prevalence of numerous previously controlled infectious diseases. The relationship between these two simultaneous phenomenabears an associativeepidemiological significance that can be explained by a decline in the U.S. population’s herd immunity. TUBERCULOSIS
The human immunodeficiency virus has been causally linked to this decade’s well-documented tuberculosis (TB) epidemic in the United States, as well as globally (5-12). Since 1953,when uniform national reporting becameimplemented in the United States, the incidence of tuberculosis had been decreasing by approximately 6% per year (13). Even with the heavy influx of infected Southeast Asians as a result of the Vietnam War, the incidence of TB had decreasedsteadily by 5.9% annually from 1963to 1985.The first substantial increase, of 2.6% (14), was observed in 1986. In New York City, reported TB cases increased by 36% from 1984to 1986,the increase being causally related by the U.S. Public Health Service to HIV (15). Although this TB epidemic can appear to be solely attributable to AIDS patients with TB and the nearly lOO-foldgreater probability (over the general population) (16, 17) of an HIV-infected person acquiring the disease, it is important to note that the increased acquisition of TB is not limited to those afflicted with HIVrelated conditions. There is an almost commensuratepercentage of persons newly diagnosed with TB but without HIV infection. According to the Centers for Disease Control statistics, 53% of 58 males ages 25-44 years without AIDS but confirmed to have Mycobacterium tuberculosis were found to be HIV seropositive (18), leaving 47% to have diseaseindependent of HIV infections. Therefore, these TB acquisitions appear to be contributing almost equivalently to the statistical increase in incidence. Tuberculosis rates can be used as one determinant to indirectly quantify the damage to a population’s herd immunity, since its pathogenicity seems to be inversely related to the immunocompetenceof its hosts. Certain institutions with increased AIDS case rates already can be used to demonstrate HIV’s effect upon the population. During 1988, the estimate aggregate reported incidence of AIDS in the U ,S. population was 13.7/100,000,whereas
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in state and federal correctional systems it was 75/100,000(19). One review of AIDS casesamong inmates in selected New York correctional facilities found TB in 6.9% of 319 persons with AIDS (20). It comes as no surprise that the incidence of TB in prisons increased 400% in the period 19761986 (21). In one Urbana, Illinois, hospital, 13health care workers were believed to have been infected with M. tuberculosis from a single AIDS patient (22). These HIV-mediated TB epidemics translate as especially threatening in the context of the total population when one considers routine transmission by the aerosol route, the increased HIV-related susceptibility, the failure of antimicrobial therapy to eliminate disease in HIV carriers even when treating susceptible strains (23), and the 6% rise in drug-resistant strains of tuberculosis since the mid-1970s (24). ATYPICAL MYCOBACTERIA
Atypical or nontuberculous mycobacteria have recently received increased scrutiny due to their significance in relation to the AIDS epidemic. Up to 53% of AIDS patients on autopsy have nontuberculous bacterial infections categorized as Mycobacterium avium complex (MAC) (25). In deference to the belief that these infections are only opportunistic, healthy young people with no evidence of impaired cellular immunity can and do acquire this disease (26); and, in contrast to those who would look upon these organisms’ transmissions as largely environmental, one review (27) cites reports that suggestperson-to-person transmissions, intrafamilial spread, and acquisition by health care workers. One outbreak in 1987 resulted in Mycobacterium chelonae infecting 17 persons as a result of contaminated ENT instruments (28). Culture analysis has shown that isolates of atypical mycobacteria in sputum of patients with associated pulmonary disease usually were different from those of the patient’s environmental strains (29), leading one to conclude that the organisms responsible for their diseasewere less likely to have been environmental in origin, leaving person-to-person transmissions a more likely source of infection. Serotype analysis has shown that certain serotypes of M. intracellulare were associated with the production of disease and these differed from the serotypes found in that environment, indicating that certain serotypes had higher pathogenicity and the human body probably served as a selective media (30). The relationship between MAC and AIDS may explain the increasing prevalence of MAC in the United States (31) due to the population’s increasing immune incompetence. Particularly disconcerting is that nontuberculous disease is being seen in increased incidence in areas considered previously to have relatively low isolation rates (Philadelphia) and among elderly females without predisposing conditions (32). The clinical observation that these infections are frequently fatal despite multiple drug regimens even in persons without underlying predisposing conditions (33) is significant; and, in those with severe immune deficits, therapy is rarely successful (34). Nontuberculous mycobacterium remain viable for long periods in the environment (35), are assumedto be spread by the air-borne route, and have been shown recently to have contaminated the water supplies of hos-
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pitals where AIDS patients are in high prevalence (36), indicating a potential for increasing nosocomial spread. SALMONELLA
Salmonellahas been recently seen in epidemic proportions in the United States (37-39). Although salmonellaoutbreaks have been attributed to Grade A eggs(40) and pasteurized milk (41), New England and the Mid-Atlantic States during the period 19761988 saw approximately an eight- to ninefold increased isolation rate for Salmonella enteritidis (42). The incidence of typhoid fever (Salmonella typhi) in the United States increased in 1989to a cumulative case rate 25% greater than the median levels for 1984-1988(43). Recent salmonella outbreaks in New York City, an area endemic for HIV, such as those at Mt. Vernon Hospital (involving 15 patients, 2 nurses, and a physician) and at Coler Memorial Hospital (that claimed 175 victims and 3 lives) (44), and a typhoid fever outbreak in the San Francisco area (45) appear to bear a geographical and associative relationship to the HIV epidemic since AIDS patients are 20 times more likely than the general population to be Salmonella carriers and most have persistent infections or recurrences despite appropriate antimicrobial therapy (46). HEPATITIS A
In the United States from 1983 to 1989 there has been a 58% increase in the incidence of reported hepatitis A infections (47,48). Were this country undergoing a major deterioration in the standard of living, sanitation, or Public Health Department activity, alternative explanations could be strongly supported; however, the increased prevalence of persons with deficient immune systemsthat allow the hepatitis A infections to be prolonged or inefficiently neutralized by protective antibody is an especially intriguing explanation since these previously unrecognized risk factors have an equally common association in that they are both likely to be associated with HIV infection. Prior to the advent of the HIV epidemic, hepatitis A had only been associated with crowding, poor personal hygiene, improper sanitation, and (less commonly) contamination of food or water and the recognized risk factors of intimate contact with infected persons, day care, and travel to underdeveloped countries. Most recently, an outbreak has been identified among at least 80 students and staff at the University of Southern California in Los Angeles (49), which is not a characteristic environment to sustain an epidemic requiring the previously cited conditions if they are considered prerequisites. A valid factor contributing to the most prolonged hepatitis A outbreak in the history of the Centers for Disease Control is probably that the source case(s) had immunosuppressioninduced by human immunodeflciency virus infection. Two of the pantry worker source casesin a study of 103 casesof hepatitis A in a Florida restaurant (50) were described as male homosexuals,promiscuous, and practitioners of anal intercourse. One had engagedin anal intercourse three to four times per month and shortly afterward acquired hepatitis B. Although all of these activities were recognized risk factors for HIV, the workers were unfortunately not
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tested for HIV; however, according to the author of the study, they “could reasonably be assumedto have been infected by HIV” (51). A large outbreak in Texas at a salad-bar restaurant (52) and two other foodborne outbreaks in Alaska were traced to homosexual male source cases (53). In the past 10 years, nearly 50% of source casesassociatedwith food-borne hepatitis A outbreaks in California have been homosexual men (54). Intravenous drug users have been only recently identified as sources of type A hepatitis in New York state and northern California (55). This association is strengthened by a geographical correlation since California and New York are the states of highest AIDS incidence. Previously it had been held that hepatitis A outbreaks were not sustained by blood-borne routes due to the short duration of the viremia. However, in persons with immunodeticiencies, it is reasonable to assume that the viremia would be prolonged enough to sustain such outbreaks and, thus, provide an explanation for this new association. CRYPTOSPORIDIOSIS
The immunity of the U.S. “herd” had been sufficient in the past to keep cryptosporidiosis at an incidence so low that it was not observed by the medical community. Prior to the advent of the AIDS epidemic it went unreported as a human pathogen in the United Statesuntil 1976(56). Only recently has this enteric pathogen been identified as one of the more common causes of intractable diarrhea among AIDS victims-being seenin as much as 15%(57) to 20% (58) of those with chronic diarrhea, but, retrospectively, can be assumed to have been contributing to the late 1970sphenomenon known as “Gay Bowel Syndrome.” In the period 1976-1981,the first seven cases of human cryptosporidiosis were reported and in five of the seven cases the patients were immunocompromised (59). Since then, it has been linked to day care centers in San Francisco (60) and elsewhere (61,62) and has infected nearly 13,000people in Western Georgia after it contaminated a water supply (63). It is highly infectious (64), can kill children (65), and can be transmitted when the spores dry out and carried through the air (66); and person-to-person spread has been documented (67). It appears that the emergence of this organism as a human pathogen in the United States has been relatively recent. Its association with the immunocompromised may have allowed it to attain sufficient concentrations in human hosts to increase its prevalence. SYPHILIS
Decreasing syphilis rates from the 1940s to the 1950swere largely due to a combination of serologic testing, public health measures, and the availability of a cure. With the often described successesin educational efforts to reduce sexual behaviors that put individuals at high risk for sexually transmitted diseases, especially HIV, one would assume that syphilis rates should still be declining; however, the opposite is true. The previous downward trends were reversed in 1987when the United States experienced at least a 25% increase over the previous year (68). Geographically, this increase has predominately occurred in areas of high HIV prevalence. Eighty-three percent of the national increase and 57% of all
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casesoccurred in New York City, California, and Florida (69). Between 1981and 1989, the incidence of primary and secondary syphilis in the United States increased 34%, from 13.7 to 18.4 cases per 100,000 persons (70), with a 9.7% increase in 1989,representing a 52% increase over the median incidence for 19841988(71). Numerous explanations have been advanced, including sexual promiscuity related to drug use, use of spectinomycin (which does not cure incubating syphilis), and decreased public health resources (72). Neglected in these explanations are the influences consequent to herd immunity decline due to the prevalence of HIV which allows those with concomitant HIV and syphilis infections (who continue to practice sexual behaviors) to transmit syphilis more efficiently. High therapeutic failure rates occur amongpatients infected with both HIV and syphilis even when recommendedlevels of antibiotics are administered (73), leading to the conclusion that spirochetes sequesteredin the central nervous system and elsewhere in the immunoincompetent can serve as sources for reinfection of the host and infection of his/her sexual contacts that would have otherwise been prevented in the presence of immunocompetence. Others have recognized an association between genital ulcer disease and HIV (74, 75). On the basis of this association, some would conclude that behavioral considerations and/or the presence of blood contact with the syphilitic ulcer predisposed the acquisition of HIV. An equally plausible explanation is that the disease causing the ulcer was present largely due to the HIV-induced loss of immunity in either the transmitter or the recipient of disease. Attempts to determine which condition preceded the other so that a cause-effect relationship can be substantiatedwould be difficult to elaborate, but the association cannot be denied. MEASLES
Measles vaccination programs were effective in steadily and markedly reducing the occurrence of this diseaseduring the years 1962-1983.However, concurrent with the AIDS Era, the period 1983 thorugh the present has seen an overall increase in measlesincidence, continuing with substantial increases in 1989(76). During 1989,a 430% increase in caseswas reported over the same period in 1988 (77). Consistent with other recent epidemics, measlesoutbreaks have been observed in areas with relatively high HIV seroprevalence, such as Los Angeles (78) and Dade County, Florida (79)) indicating (in the absenceof a more virulent organism) a loss in herd immunity to measles demographically associated with relatively high HIV prevalence. The larger part of this epidemic occurrence cannot be explained on the basis of an increasingfailure to have children immunized. In 1988,68.9%of reported cases occurred among school-age children who had been previously vaccinated and most vaccine failures occurred in persons 12-19 years of age (80) who earlier were believed to be sufficiently protected. HIV-infected persons with measlesdo not necessarily demonstrate the typical, diagnostic rash (81). Therefore, these carriers can serve as more efficient sources of outbreaks for longer periods becausethe absenceof typical clinical symptoms
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precludes diagnosis, thereby delaying or preventing initiation of treatment, outbreak control measures, or appropriate isolation procedures (82). It is likely that a substantial number of HIV-infected individuals transmit the measles virus due to a failure of vaccine-induced humoral immunity. This phenomenon has been described in a previously immunized 16year-old HIV carrier who had been immunized with live-attenuated measlesvaccine at 15 months and again at 9 years of age yet still developed serologically confirmed measles (83). In deference to claims that a primary vaccine performance failure may be responsible (84), it is reasonable to assume that a stable rate of individual vaccine performance failures had been present throughout the history of measles immunization programs; yet a failure had not been observed because the prevalence of the measlesvirus was kept low enough by national vaccine performance (induced herd immunity) to prevent the percentage of poor vaccine responders from being epidemiologically observed. However, when higher numbers of measles carriers exist in the population, the statistical probability of an inadequately immunized individual (either from a primary vaccine failure or a waning of vaccine-induced immunity) being exposed, infected, and becoming infectious correspondingly increases. An increase in infections among previously immunized persons would not have been observed if the herd immunity had remained constant or increased. By exclusion, this event could only have occurred in the presence of a reduction in herd immunity. INFLUENZA
A reduction in herd immunity also serves to explain the currently and continuously increasing influenza activity (85). The mortality from pneumonia and influenza reported by vital records offices in 121 U.S. cities recorded from 1979 through 1989has shown a progressive increase from approximately 3.5 to 5.5% (86). Data from the Centers for Disease Control have shown that during the 1980s the number and percentage of deaths attributable to pneumonia and influenza among persons ages 25-44 years more than doubled in cities with high AIDS incidence (87). Nationally, the number of deaths from influenza and pneumonia during 1988was higher than that for the preceding 4 years. The association with AIDS and influenza is significant enough for some authors to advocate annual immunization of the HIV-infected’s household contacts (88). Again, it has been shown that more than half of persons with AIDS or ARC (AIDS-related complex) do not produce antibodies considered to be protective in response to four different influenza vaccines (89). It can be assumed, then, that once infected by the initial wild-type influenza virus, the HIV-afflicted host will retain and be infectious for this organism for significantly longer periods than their immunocompetent counterparts. DISCUSSION
When members of a population with faulty immune systems are increasingly distributed throughout a population, the incidence and prevalence of other communicable diseases increase as herd immunity declines. No single factor better serves to explain the multiple epidemic increases being seen in the United States
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since the advent of the AIDS Era than the effect of HIV itself. If the abovedescribed epidemics were the only infectious diseaseconsequencesto be considered, the population damage occasioned by the destruction of herd immunity might be limited to a degree commensuratewith society’s ability to managethese select organisms. However, these epidemics may be serving as currently quantifiable heralds for the human population’s profound future interaction with all infectious diseasesif preemptive measuresare not employed. Because immunocompetence exists more as a spectrum of varying degree rather than as a qualitative distinction and because susceptibility to morbidity depends upon variable genetic, environmental, and other pathogenic influences, that large segmentsof the population have preexisting disease or are relatively immunosuppressed for a wide variety of reasons exclusive of HIV infections cannot be ignored. Especially at risk in an era of declining herd immunity are the young, pregnant women, the elderly, and those with chronic disease. The propensity for the HIV-infected to influence the transmission of diseasefor even those pathogens generally accepted to be exclusively opportunistic has been shown in relation to Pneumocystis carinii pneumonia. In a Texas cancer center, a nearly dose-related infection acquisition response in cancer patients that increasedwith the number of AIDS admissionsand declined equivalently when the number of AIDS registrations fell was observed (90). Beyond direct diseasetransmissions there are other less obvious ramifications to be considered as herd immunity is compromised. A substantial number of currently used serologic screensand diagnostic modalities rely upon humoral and cell-mediated immunocompetencefor proper function at both the individual and the population level. As a population’s immunocompetenceis lost, modem medicine’s ability to cheaply and efficiently screen for the presence or absence of disease is jeopardized. In the case of tuberculosis, anergy to skin testing is seen in up to 29% of AIDS patients (91) and the absenceof cavitations on chest X-ray cannot be relied upon since this is a cell-mediated response and distinctly uncommon in AIDS (92). Hicks et al. (93) have described this phenomenon wherein HIV-infected patients’ faulty immune systems fail to produce sufficient antibody against treponemal antigens to allow seropositivity to be recognized on the standard tests (VDRL and FTA-ABS) that rely upon these antibodies for proper function. Societies that have come to rely upon these types of sophisticated medical technologies can expect a substantial quantity of disease to go undetected for longer periods, giving rise to both prolonged carrier states and increased frequencies of infectious transmissions. Also, the ability to induce and benefit from the herd immunity that has served as a basis for broad-basedvaccination strategies(94) will be significantly impaired as a consequence of the HIV epidemic’s influence. The effort to increase herd immunity has long been evoked as a justification for mandatory immunization programs that require children to be vaccinated against diseasesbefore allowing them to enter schools. Acting upon that logic was demonstrably successful. As with measles,diseaseresurgence has also been observed with regard to mumps.
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During the period 1985-1987,the annual incidence rate rose almost fivefold (95), and 1989 saw a 15% increase over the previous year (96). The human population can expect a future increase not only in the numbers of sameserotype epidemics but also in the number of serologically different epidemics. This can be predicted because the bulk of human infectious diseases do not reproduce in the environment. They require human hosts in which to undergo the successiveand successful mutations that allow antigenic drift and shift to occur. One limiting factor in the rate of antigenic shift or drift is the immunity generated by individuals in the population that eradicates the organisms from the host prior to their production of new immunologically distinct strains. These strains most probably originate in hosts, and it is logical to assume that they originate in humans who are infected with the progenitor strain. When a declining herd immunity allows pathogens to thrive for prolonged periods of time and the number of human hosts to increase, the statistical probability that new serotypes will develop can only be increased. HIV infections in the hosts provide precisely that environment by preventing an appropriate immune response from eradicating the organisms before they undergo sufficient mutational events that allow the creation of novel, serologically distinct strains. It is not unreasonable to consider that the use of live-attenuated viral vaccines in the HIV-infected might be allowing the production of subclinical infections with reversion mutations that are as transmissible and pathogenic as the original strains. The HIV itself appears to capitalize upon its induction of immunoincompetence combined with a prolonged duration of infection and propensity for mutagenicity to produce variant surface morphologies that allow increased infectivity and the creation of successiveHIV serotypes that require specific immune responseseach more progressively difficult to generate in order to effect successful antibody neutralization. This prolonged period of virus presence that predisposes an increased opportunity for viral mutagenicity and variant clone creation has been previously described in relation to a continuous varicella-zoster infection in a child with AIDS who developed an acyclovir resistance during the course of her treatment (97), an acyclovir-resistant herpes simplex in AIDS patients (98), and a ganciclovirresistant cytomegalovirus in AIDS patients (99). These findings raise the specter of yet another threat (100) to the ability of “the herd” to avoid associated disease and are consistent with the recently increasing frequency and rapid development of antimicrobial resistance in both viruses (101) and bacteria (102, 103). CONCLUSION
Out of necessity, the HIV epidemic causes us to reevaluate the relationships that individuals have with their society and how society relates to its members in the context of infectious disease. The belief that our society had evolved beyond the catastrophic consequencesof infectious diseaseshas had to be abandoned in light of the entry of the human immunodeficiency virus into the grand equation of life and death. At the very least, the epidemiological findings of temporal, risk group, and geographical associations make the relationship between the HIV
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epidemic and superimposed secondary epidemics worthy of heightened epidemiological exploration and intervention. These considerations may require a reexamination of the function and designation of institutions, facilities, equipment, procedures, and even laws that our society designed in a past era of heightened herd immunity. Vaccination recommendations (such as BCG inoculation, repetitive measles boosters, influenza vaccine) must evolve to bolster the immunity in health care workers, prisoners, prison employees, or any others routinely exposed to populations with high HIV carrier rates. Since HIV will undoubtedly influence the epidemiology of communicable diseases (especially as they relate to subsequent environmental transmissions of enteric pathogens) public health departments should consider including preferential investigative HIV testing of source casesin local infectious diseaseoutbreaks and those persons in the food service industry implicated in outbreaks of any food-borne pathogen. In addition, frequent laboratory and/or clinical monitoring of HIV-infected health care, child care, or food service employees should be implemented so that, if infected with a communicable superimposedsecondary infection (whether specifically symptomatic or not), they can be removed from that environment until it can be demonstrated that they no longer pose a risk for contagion. Ultimately, a strategy of confidential HIV testing, identification, and monitoring of the infected (whenever an individual’s contact can be seen to put other persons at risk) would efficiently allow a focused surveillance for the HIV-related superimposed secondary infections and would be cdrrtistent with a public health policy that places a priority on disease prevention. It must realize that HIV carriers, too, are at especially higher risk of acquiring superimposeddiseasewhen they are in contact with any population experiencing a reduction in herd immunity. Without question, the HIV carriers would benefit by limiting their exposure to pathogens as well as by being afforded the opportunity for early diagnosis and treatment (particularly those unaware that they are infected with superimposed secondary infections). Most certainly, the HIV-uninfected majority of society would benefit since the transmission of technologically preventable diseasewould be significantly reduced. REFERENCES 1. Vento S, Di Petri G, et al. Reactivation of hepatitis B in AIDS. Lancer 1989; 2:109-110. 2. Lynch JP. When opportunistic viruses infiltrate the lung. .I Respir Dis 1989; 10~25-30. 3. Reuler JB, Chang MK. Herpes zoster: Epidemiology, clinical features, and management. Sourh Med J 1984; 77(9): 1149-1156. 4. Tuberculosis and acquired immunodeficiency syndrome-New York City. MMWR 1987; 36(48):785-795. 5. Harries AD. Tuberculosis and human immunodeliciency virus infection in developing countries.
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36. Stine TM, Harris AA, et al. A pseudoepidemic due to atypical mycobacteria in a hospital water supply. JAMA 1987; 258(6):809-811. 37. Ryan CA, Nickels MK, et al. Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk. JAMA 1987; 258(22):3269-3274. 38. St. Louis ME, Morse DL, Potter ME, et al. The emergence of grade A eggs as a major source of Salmonella enteritidis infections. JAMA 1988; 259:2103-2107. 39. Centers for Disease Control. Increasing Rate of Salmonella enteritidis infections in the northeastern United States. MMWR 1987; 36(1):1&11. 40. St. Louis, op. cit., p. 2103. 41. Ryan, op. cit., p. 3269. 42. Centers for Disease Control. Update: Salmonella enteritidis infections and grade A shell eggsUnited States, 1989. MMWR 1989; 38(51, 52):877-880. 43. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 44. Editor. Third patient dies of salmonella poisoning. American Medical News, September 4, 1987:63. 45. Bodovitz K. East Bay officials seek source of typhoid cases. San Francisco Chronicle, August 26, 1988. 46. Laurence J. Gastrointestinal infections in AIDS patients. Infect Med 1986; October:318-326. 47. Centers for Disease Control. Summary-Cases of Notifiable Diseases, United States. MMWR 1990; 38(51, 52):891. 48. Data supplied by Craig N. Shapiro, M.D., Medical Epidemiologist, Public Health Service, Hepatitis Branch Div. of Viral and Rickettsial Diseases, Centers for Disease Control, Atlanta, as reported in San Francisco Chronicle, 4115190. 49. Los Angeles Daily News, Hepatitis A Outbreak in Los Angeles, 12/28/1989, quoting Donnell Ewert of LA County Health Department. 50. Lowry PW, Levine R, et al. Hepatitis A outbreak on a floating restaurant in Florida, 1986. Am J Epidemiol 1989; 129(1):155-164. 51. Lowry PW, Personal communication, November 21, 1989. 52. Centers for Disease Control. Food-borne hepatitis A-Oklahoma, Texas. MMWR 1983; 32:652659. 53. Kosatsky T, Middaugh JP. Linked outbreaks of hepatitis A in homosexual men and in food service patrons and employees. West J Med 1986; 144~307-310. 54. Lowry PW, Levine R, et al. Hepatitis A outbreak on a floating restaurant in Florida, 1986. Am J Epidemiol 1989; 129(1):163. (quoting personal conversation with Dr. R. Roberto, CA Department of Health Serv., 1987) 55. Hepatitis A among drug abusers. MMWR 1988; 37:297-300, 305. 56. Nime FA, Burek JD, Page DL, et al. Acute enterocolitis in a human being infected with the protozoan Cryptosporidium. Gastroenterology 1976; 70~592-598. 57. Smith PD, Lane HC, Gill VJ, et al. Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Ann Zntern Med 1988; 108:328-333. 58. Nelson JA, Reynolds-Kohler C, Margaretten W, et al. Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms. Lancet 1988; 1:259-262. 59. Soave R, Armstrong D. Cryptosporidium and cryptosporidiosis. Rev Znfect Dis 1986; 8(6):10121023. 60. Infectious Disease Section California State Department of Health Services. Cryotosporidiosis: A newly recognized cause of diarrheal illness in day care centers. California Morbidity Weekly Report 1984; 41, October 19:l. 61. Alpert G, et al. Outbreak of cryptosporidiosis in a day care center. Pediatrics 1986; 77:1X2-157. 62. Gallaher M. Cryptosporidiosis outbreak linked to day-care center. Am J Public Health 1988; 7939-42. 63. Hayes EB, Matte TD, O’Brien TR, et al. Large community outbreak of cryptosporidiosis due to contamination of a faltered public water supply. N Engl J Med 1989; 328~1372-1376. 64. Soave, op. cit., p. 1015. 65. Peck P. Animal rights: Terrorists strike medicine. Physician’s Management 1989; June:49-68.
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66. Ibid. 67. Koch KL, Phillips DJ, Aber RC. Cryptosporidiosis in hospital personnel; evidence for personto-person transmission. Ann Intern Med 1985; 102:593-5%. 68. Centers for Disease Control. Syphilis and congenital syphilis-United States 1985-1988.MMWR 1988; 37486. 69. Centers for Disease Control. Continuing increase in infectious syphilis-United States. JAMA 1988; 259(7):975-977. 70. Rolfs RT, Nakashima AK. Epidemiology of primary and secondary syphilis in the United States, 1981through 1989. JAMA 1990; X4(11):1432. 71. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 72. Centers for Disease Control. Continuing increase in infectious syphilis-United States. JAMA 1988; 259(7):975-977. 73. McGuire R. Neurosyphilis: Menacing AIDS companion. Medical Tribune 1989;January 193-18. 74. Simonsen JN, Cameron DW, Gakinya MN, ef al. Human immunodeficiency virus infection among men with sexually transmitted disease: Experience from a center in Africa. N Engl J Med 1988; 319:274. 75. Stamm WE, Handslield HH, Rompalo AM, ei al. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA 1988; 260:1429. 76. Centers for Disease Control. Measles-United States, 1988. MMWR 1989;38(35):601~5. 77. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 78. Centers for Disease Control. Measles-Los Angeles County, California, 1988. MMWR 1989; 38(4):49-57. 79. Centers for Disease Control. Measles-Dade County Florida. MMWR 1987; 3ti45-48. 80. Ibid., p. 603. 81. Krasinski K, Holzman RS, Lacouture R, et al. Nosocomial measles: Are current vaccination guidelines for staff adequate? (Abstract). In: Program and Abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4-7, 1987. Described in: CDC, Measles in HIV-Infected Children, United States. MMWR 1988; 37(11, 12) (Obtained from JAMA) Leads from MMWR 1988; 259(16):2352-2357. 82. Enders JF, McCarthy K, Mitus A, Cheatham WJ. Isolation of measles virus at autopsy in cases of giant-cell pneumonia without rash. N Engl. J Med 1959; 261:875-881. 83. Centers for Disease Control. Measles in HIV-infected children, United States. MMWR 1988; 37(11, 12) (Obtained from JAMA) Leads from MMWR 1988; 259(16):2352-2357. 84. Markowitz LE, Preblud SR, Fine PEM, Orenstein WA. Duration of live measles vaccine-induced immunity. Pediutr Infect Dis J, in press. From: CDC, Measles-United States, First 26 Weeks, 1989. MMWR 1989; 38:863-872. 85. Centers for Disease Control. Influenza Activity-United States, 1989.MMWR 1989; 3k863-872. 86. Tipple MA, Kendal AP. Influenza epidemiology: Lessons from recent outbreaks. J Respir Dis Suppl. Influenza in the 1990’s: Use of Antiviral Agents in Prophylaxis and Treatment 1989; December:Sll. 87. Centers for Disease Control. Increase in pneumonia mortality in young adults and the HIV epidemic in New York City, United States. MMWR 1988; 32593. 88. Nelson KE. Annual influenza vaccination indicated for HIV-infected patients. Medical Aspects of Human Sexuality 1989; December:l. 89. Nelson KE, Clements ML, Miotti P, et al. The influence of HIV infection on antibody responses to influenza vaccines. Ann Intern Med 1988; 109:383. 90. Haron E, Bodey GP, Luna MA, et al. Has the incidence of Pneumocystis carinii pneumonia in cancer patients increased with the AIDS epidemic? Lancer 1988; 2904-905. 91. Mann J, Snider DE, Francis H, et al. Association between HTLV-III/LAV infection and tuberculosis in Zaire. JAMA 1986; 256(3):346. 92. Anon. TB making a comeback as AIDS-related pathogen. Med World News 1986; July 28:61. (Quoting Dr. Philip Hopewell, University of California, San Francisco)
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93. Hicks CB, Benson PM, Lupton GP, et al. Seronegative secondary syphilis in a patient infected with the human inununodeficiency virus (HIV) with Kaposi sarcoma. Ann Zntern Med 1987; lOT492-495. 94. Centers for Disease Control. Prevention and control of influenza. MMWR 1988; 37:361-364, 369-373. 95. Centers for Disease Control. Mumps prevention. MMWR 1989; 38(22):388-t00. %. Centers for Disease Control. Summary-Cases of specified notifiable diseases, United States. MMWR 1990; 38(52):891. 97. Pahwa S, Biron K, Lim W, et al. Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA 1988; 260(19):2879-2882. 98. Erlich KS, Mills JM, Chatis P, Mertz GJ, et al. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320(5):293-2%. 99. Erice A, Chou S, Biron KK, Stanat SC, et nl. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N Engl J Med 1989; 32q5):289-293. 100. Zoler ML. Hospital infections got tougher. Medical World News 1990; September:12-13. 101. Norris SA, Kessler HA, Fife KH. Severe, progressive herpetic whitlow caused by acyclovirresistant virus in a patient with AIDS. J Infect Dis 1988; 157:209-210. 102. Handwerger S. Bacterial resistance to antibiotics seen increasing. Mod Med 1989; February(57):37. 103. Schwartz SK, Zenilman JM, et al. National surveillance of antimicrobial resistance in Neisseria gonorrhoeae. JAMA 1990; X4(11):1413-1417. Received June 15, 1990 Revised September 28, 1990 Accepted October 9, 1990