HIV fulfills Koch's postulates as the cause of AIDS.
Among many criteria used over the years to prove the link between putative pathogenic (disease-causing) agents and disease, perhaps the most-cited are Koch's postulates, developed in the late 19th century. Koch's postulates have been variously interpreted by many scientists, and modifications have been suggested to accommodate new technologies, particularly with regard to viruses (Harden. Pubbl Stn Zool Napoli [II] 1992;14:249; O'Brien, Goedert. Curr Opin Immunol 1996;8:613). However, the basic tenets remain the same, and for more than a century Koch's postulates, as listed below, have served as the litmus test for determining the cause of any epidemic disease:
1. Epidemiological association: the suspected cause must be strongly associated with the disease.
2. Isolation: the suspected pathogen can be isolated - and propagated - outside the host.
3. Transmission pathogenesis: transfer of the suspected pathogen to an uninfected host, man or animal, produces the disease in that host.
With regard to postulate #1, numerous studies from around the world show that virtually all AIDS patients are HIV-seropositive; that is they carry antibodies that indicate HIV infection. With regard to postulate #2, modern culture techniques have allowed the isolation of HIV in virtually all AIDS patients, as well as in almost all HIV-seropositive individuals with both early- and late-stage disease. In addition, the polymerase chain (PCR) and other sophisticated molecular techniques have enabled researchers to document the presence of HIV genes in virtually all patients with AIDS, as well as in individuals in earlier stages of HIV disease.
Postulate #3 has been fulfilled in tragic incidents involving three laboratory workers with no other risk factors who have developed AIDS or severe immunosuppression after accidental exposure to concentrated, cloned HIV in the laboratory. In all three cases, HIV was isolated from the infected individual, sequenced and shown to be the infecting strain of virus. In another tragic incident, transmission of HIV from a Florida dentist to six patients has been documented by genetic analyses of virus isolated from both the dentist and the patients. The dentist and three of the patients developed AIDS and died, and at least one of the other patients has developed AIDS. Five of the patients had no HIV risk factors other than multiple visits to the dentist for invasive procedures (O'Brien, Goedert. Curr Opin Immunol 1996;8:613; O'Brien, 1997; Ciesielski et al. Ann Intern Med 1994;121:886).
In addition, through December 1999, the CDC had received reports of 56 health care workers in the United States with documented, occupationally acquired HIV infection, of whom 25 have developed AIDS in the absence of other risk factors. The development of AIDS following known HIV seroconversion also has been repeatedly observed in pediatric and adult blood transfusion cases, in mother-to-child transmission, and in studies of hemophilia, injection-drug use and sexual transmission in which seroconversion can be documented using serial blood samples (CDC. HIV AIDS Surveillance Report 1999;11[2]:1; AIDS Knowledge Base, 1999). For example, in a 10-year study in the Netherlands, researchers followed 11 children who had become infected with HIV as neonates by small aliquots of plasma from a single HIV-infected donor. During the 10-year period, eight of the children died of AIDS. Of the remaining three children, all showed a progressive decline in cellular immunity, and two of the three had symptoms probably related to HIV infection (van den Berg et al. Acta Paediatr 1994;83:17).
Koch's postulates also have been fulfilled in animal models of human AIDS. Chimpanzees experimentally infected with HIV have developed severe immunosuppression and AIDS. In severe combined immunodeficiency (SCID) mice given a human immune system, HIV produces similar patterns of cell killing and pathogenesis as seen in people. HIV-2, a less virulent variant of HIV which causes AIDS in people, also causes an AIDS-like syndrome in baboons. More than a dozen strains of simian immunodeficiency virus (SIV), a close cousin of HIV, cause AIDS in Asian macaques. In addition, chimeric viruses known as SHIVs, which contain an SIV backbone with various HIV genes in place of the corresponding SIV genes, cause AIDS in macaques. Further strengthening the association of these viruses with AIDS, researchers have shown that SIV/SHIVs isolated from animals with AIDS cause AIDS when transmitted to uninfected animals (O'Neil et al. J Infect Dis 2000;182:1051; Aldrovandi et al. Nature 1993;363:732; Liska et al. AIDS Res Hum Retroviruses 1999;15:445; Locher et al. Arch Pathol Lab Med 1998;22:523; Hirsch et al. Virus Res 1994;32:183; Joag et al. J Virol 1996;70:3189).
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