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A total of 4,626 mammals were serologically tested for antibodies to Sin Nombre virus. All nonrodent species were antibody negative. Among wild rodents, antibody prevalence was 8.5% in murids, 1.4% in heteromyids, and < 0.1% in sciurids. Of 1,921 Peromyscus maniculatus (deer mice), 226 (11.8%) were antibody positive, including one collected in 1975. The highest antibody prevalence (71.4% of 35) was found among P. maniculatus on Santa Cruz Island, off the southern California coast. Prevalence of antibodies among deer mice trapped near sites of human cases (26.8% of 164) was significantly higher than that of mice from other sites (odds ratio = 4.5; 95% confidence interval = 1.7, 11.6). Antibody prevalence increased with rising elevation (> 1,200 meters) and correlated with a spatial cluster of hantavirus pulmonary syndrome cases in the Sierra Nevada.

Objective: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population.Participants: The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies.Evidence: MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources.Consensus Process: Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft.Conclusions: A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period. [ABSTRACT FROM AUTHOR]

Objective: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population.Participants: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine.Evidence: The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement.Consensus Process: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members.Conclusions: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing. [ABSTRACT FROM AUTHOR]

Objective: This study sought to identify risk factors associated with an unfavorable outcome after elective abdominal aortic aneurysm (AAA) repair in patients with chronic obstructive pulmonary disease (COPD)., Methods: The clinical records of 158 patients who underwent elective open AAA repair with COPD determined from preadmission International Classification of Diseases-ninth revision codes during a 12-year period at the University of Michigan were reviewed. Patients with uncomplicated outcomes (group I) were compared with those with unfavorable postoperative outcomes (group II). The unfavorable outcomes were defined as myocardial infarction, acute renal failure, worsening respiratory insufficiency necessitating tracheostomy, or death within 30 days of surgery. Logistic regression analyses of variables that were identified as being statistically significant in the univariate analysis were used to develop a predictive model of these events., Results: Group I included 133 patients (77 men, 56 women) with a mean age of 70.1 years, and group II included 25 patients (13 men, 12 women) with a mean age of 71.4 years. Preoperative factors statistically related (P =.002) to an unfavorable outcome in group II patients included: suboptimal COPD management (fewer prescribed inhalers), lower hematocrit, preoperative renal insufficiency, and coronary artery disease. Importantly, abnormal preoperative spirometry and arterial blood gases were not predictive of a poor outcome. Univariate analysis also revealed increased hospital (25 versus 13 days; P =.0001) and intensive care unit (14 versus 4 days; P =.001) length of stays and a greater need for prolonged ventilation (8 versus 1 day; P =.039) for group II patients compared with group I patients. The 30-day mortality rate in the entire experience was 3.2% (5/158). No specific variables associated with mortality were identified., Conclusion: Fewer prescribed inhalers, lower hematocrit, renal insufficiency, and coronary artery disease are preoperative factors associated with unfavorable outcomes after open elective surgical repair of AAA in patients with COPD. Intensive management of these factors may reduce the hazards of AAA operations in these patients. COPD alone should not be considered a deterrent to the surgical treatment of AAAs.

Objective: To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population., Participants: The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions., Evidence: MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed., Consensus Process: Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft., Conclusions: Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

Objective: To review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population., Participants: The working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies., Evidence: MEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources., Consensus Process: The first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations., Conclusions: Specific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.

Objective: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population., Participants: The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies., Evidence: MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000., Consensus Process: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members., Conclusions: An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.

Objective: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of smallpox as a biological weapon against a civilian population., Participants: The working group included 21 representatives from staff of major medical centers and research, government, military, public health, and emergency management institutions and agencies. Evidence The first author (D.A.H.) conducted a literature search in conjunction with the preparation of another publication on smallpox as well as this article. The literature identified was reviewed and opinions were sought from experts in the diagnosis and management of smallpox, including members of the working group., Consensus Process: The first draft of the consensus statement was a synthesis of information obtained in the evidence-gathering process. Members of the working group provided formal written comments that were incorporated into the second draft of the statement. The working group reviewed the second draft on October 30, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members., Conclusions: Specific recommendations are made regarding smallpox vaccination, therapy, postexposure isolation and infection control, hospital epidemiology and infection control, home care, decontamination of the environment, and additional research needs. In the event of an actual release of smallpox and subsequent epidemic, early detection, isolation of infected individuals, surveillance of contacts, and a focused selective vaccination program will be the essential items of an effective control program.

Objective: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of anthrax as a biological weapon against a civilian population., Participants: The working group included 21 representatives from staff of major academic medical centers and research, government, military, public health, and emergency management institutions and agencies., Evidence: MEDLINE databases were searched from January 1966 to April 1998, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of references identified by this search led to identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources., Consensus Process: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. Members of the working group provided formal written comments which were incorporated into the second draft of the statement. The working group reviewed the second draft on June 12, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members., Conclusions: Specific consensus recommendations are made regarding the diagnosis of anthrax, indications for vaccination, therapy for those exposed, postexposure prophylaxis, decontamination of the environment, and additional research needs.

To estimate the prevalence and predictors of hepatitis C virus (HCV) infection among inmates, a cross-sectional survey was conducted in 1994 among inmates entering six reception centers of the California Department of Corrections. Discarded serum samples were tested for antibodies to human immunodeficiency virus (HIV), HCV, hepatitis B core, and hepatitis B surface antigen (HBsAg). Of 4,513 inmates in this study, 87.0% were men and 13.0% were women. Among male inmates, 39.4% were anti-HCV-positive; by race/ethnicity, prevalences were highest among whites (49.1%). Among female inmates, 53.5% were anti-HCV-positive; the prevalence was highest among Latinas (69.7%). In addition, rates for HIV were 2.5% for men and 3.1% for women; and for HBsAg, 2.2% (men) and 1.2% (women). These data indicate that HCV infection is common among both men and women entering prison. The high seroprevalence of anti-HCV-positive inmates may reflect an increased prevalence of high-risk behaviors and should be of concern to the communities to which these inmates will be released.

The central paradox of HIV pathogenesis is that the viral burden, either free or cellular, seems too low to deplete the CD4 population by direct killing. Until recently, little data could be used to compare direct and indirect pathogenic theories critically. Clinical trials with potent new antiviral agents have measured important kinetic parameters of HIV infection, including viral and infected cell half-lives. This has led to the construction of explicit models of direct killing. Using a worst-case dynamic analysis, we show that such cytopathic models are untenable. Rates of infected cell removal are orders of magnitude too low to suppress steady state CD4 counts significantly in the face of lymphocyte replenishment, especially in early infection. Furthermore, the direct cytopathic models, as proposed, predict an extremely variable disease course across the broad range of observed viral burdens (five orders of magnitude), which is inconsistent with the relatively small differences in disease progression observed between patients. In contrast, immunologic theories of pathogenesis, such as homeostatic dysregulation based on immune activation, do not suffer from these difficulties and are more consistent with the natural history of HIV infection.

Plasma samples from HIV-infected (HIV+) rapid progressors (RP) and nonprogressors (NP) in the San Francisco Men's Health Study showed significantly elevated levels of RANTES but not macrophage inflammatory protein 1 (MIP1) alpha or MIP1 beta in comparison to HIV-seronegative (HIV-) controls. In 32 individuals who became infected with HIV during the course of this study, RANTES levels were significantly higher in plasma samples collected at the time antibodies to HIV were first detected than in pre-seroconversion plasma samples. Both RP and NP showed significant temporal increases in plasma RANTES concentrations. No significant associations were observed, however, between plasma levels of these chemotactic cytokines and progression or known predictors of progression to AIDS including viral burden, levels of beta 2-microglobulin or neopterin, and levels of activated CD8+ lymphocytes. These findings are consistent with the results of a number of recent reports which suggest that these chemokines do not play a major systemic role in the long-term control of viremia or protection against the progression of HIV disease. It remains possible that chemotactic cytokines may contribute locally to control HIV in lymph nodes or other organs but it is also possible that they may be mediators of potentially harmful inflammatory responses.

We evaluated the associations of specific recreational drugs and alcohol with laboratory predictors of AIDS at entry into the San Francisco Men's Health Study (SFMHS) in 1984 and with the development of the acquired immunodeficiency syndrome (AIDS) during 6 years of follow-up. Marijuana use was associated with a decreased rate of progression to AIDS in the univariate analysis (RR = 0.7; P = 0.01). Marijuana use was more common among individuals with elevated HIV viral core protein antibody (p24Ab) titer (> 1:16) at baseline (P = 0.03); this finding suggests that marijuana users were healthier at baseline. When the data were adjusted for p24 Ab and other laboratory parameters, no association with progression to AIDS was observed for marijuana, suggesting that the observed univariate result was due to a difference in HIV-related disease at the time of enrollment. No statistically significant associations were observed for nitrites, methylene dioxyamphetamines, ethyl chloride, downers, cocaine, stimulants, narcotics, or psychedelic drugs. These data suggest no substantial association between use of these drugs and the development of AIDS among HIV-infected men.

Sin Nombre virus (SNV) causes the zoonotic disease hantavirus pulmonary syndrome (HPS). Its mechanisms of transmission from rodent to human are poorly understood. It is possible that specific genetic signature sequences could be used to determine the probable site of each case-patient's exposure. Environmental assessments suggested 12 possible sites of rodent exposure for 6 HPS patients. Rodents were captured at 11 of the 12 sites and screened for SNV infection within 2 weeks of the patient's diagnosis. Viral sequences amplified from tissues of rodents at each site were compared with those from case-patients' tissues. Rodents bearing viruses with genetic sequence identity to case-patients' viruses across 2 genomic segments were identified in 4 investigations but never at >1 site. Indoor exposures to rodents were especially common at implicated sites. By distinguishing among multiple possible sites of exposure, viral genotyping studies can enhance understanding of the conditions associated with infection by SNV.

A flow cytometric assay based on expression of the activation antigen CD69 was developed to analyze immunological responses of T cells from human immunodeficiency virus (HIV)-infected (HIV+) or HIV-seronegative (HIV-) donors after in vitro simulation by antigens and polyclonal activators. The levels of CD69 on freshly-isolated or unstimulated, cultured CD3+, CD4+, or CD8+ peripheral blood lymphocyte (PBL) subsets were low and did not differ greatly between HIV+ and HIV- donors. The frequencies of CD3+, CD4+, and CD8+ lymphocytes from HIV+ donors that expressed CD69 after culture with antigenic or mitogenic stimuli were significantly lower than in HIV- donors. Comparison of CD69 expression with [3H]thymidine incorporation revealed that both assays could detect lymphocyte responses to antigenic or mitogenic stimuli. The CD3+ PBL from HIV+ or HIV- donors did not show increased CD69 expression after culture with soluble or cross-linked recombinant envelope glycoprotein, gp120. The gp120, however, significantly inhibited CD69 expression in phytohemagglutinin-stimulated T cells in vitro and may also affect T-cell activation in vivo. These studies demonstrate the usefulness of this CD69 expression assay for the rapid assessment of defects in immune responses of phenotypically defined lymphocyte subsets in HIV+ patients and for testing the effects of agents that modulate immune activation.

A fatal case of hantavirus pulmonary syndrome (HPS) in northern California prompted our attempt to isolate viruses from local rodents. From tissues of two deer mice, Peromyscus maniculatus, two hantaviruses (Convict Creek virus 107 and 74, CC107 and CC74) were established in cell culture. Viral antigens, proteins, and RNAs of the first and archetypical isolate (CC107) were examined, and portions of the medium (M) and small (S) genome segments of both isolates were sequenced. Antigenically, CC107 virus and the second isolate, CC74 virus, were more closely related to Puumala virus than Hantaan (HTN) virus, though distinct from both. Northern blots of viral RNAs showed the large and M segments of CC107 to be the same size as those of HTN virus, whereas the S segment was larger. Protein gels did not reveal CC107 to have a substantially larger nucleocapsid protein than HTN virus. Partial nucleotide sequence comparisons of CC107 and CC74 viruses revealed their M segments to be highly similar to one another, while their S segments differed by more than 10%. Nucleotide and deduced amino acid sequence comparisons showed the California isolates to be closely related to the newfound hantaviruses first detected in the Four Corners area and since incriminated in HPS through wide areas of the United States.

Immune system activation is gaining attention as a central part of HIV pathogenesis. Although there is no consensus yet as to the source of the signal or the result of the signalling, this line of thinking represents a significant shift in the paradigm away from considering HIV disease like any other cytopathic viral infection. Hopefully, completion of studies focussed on this approach will lead to more complete understanding of AIDS and more effective therapies, and will at least bring to the fore some of the central unanswered questions in modern cellular immunology.

We report two cases of hantavirus pulmonary syndrome that were probably acquired in California. Genetic analysis of tissue specimens from one of the patients revealed that the virus isolated is a variant of the strain (Sin Nombre virus) identified in the outbreak of hantavirus pulmonary syndrome that occurred in the Four Corners region of the southwestern United States in 1993. In addition to presenting the clinical features of the two cases, we discuss the possible risk factors for infection.

Objective: To identify and characterize individuals with long-term HIV-1 infection who have experienced little or no progressive CD4+ T-cell loss during follow-up., Patients and Methods: The rate of CD4+ T-cell loss (CD4 slope) was determined for each of the 290 participants in the San Francisco Men's Health Study who were seropositive at study entry in 1984. The study population was stratified, by CD4 slope, into 10 groups of 29 individuals and each group was characterized using a variety of cross-sectional and longitudinal laboratory measurements., Results: Approximately 10% of the HIV-1-infected men experienced no net CD4+ T-cell loss during 78 months of follow-up. Compared with all other seropositive subjects, these 'non-progressors' were the extreme cases in a relatively continuous distribution of CD4 slopes, rather than a discrete subpopulation. Although they had no net cell loss, their mean CD4+ cell count was approximately 400 x 10(6)/l lower and their mean CD8+ cell count approximately 250 x 10(6)/l higher than seronegative subjects, suggesting early changes followed by stabilization. The CD4 slope was associated with the levels of beta 2-microglobulin, neopterin, p24 antibody, erythrocyte sedimentation rate, viral burden, and the proportion of HIV-1 isolates with tropism for the MT-2 T-cell line. Multivariate cluster analysis of these laboratory markers did not distinguish the non-progressors as a distinct subgroup., Conclusions: These findings support both a biphasic natural history and the suggestion that the broad range in HIV disease progression rates may be the result of several independent factors interacting in a variety of combinations. Recent changes in laboratory markers, known to predict both CD4+ cell loss and AIDS, suggest that non-progressors are undergoing slow HIV disease progression.

A hypothesis identifying substance abuse as a main cause of AIDS has naturally excited much publicity. But such claims have no basis in fact.

Infection with HIV-1 and < 200 CD4+ lymphocytes/mm3 has been proposed as an AIDS-defining condition. We have evaluated the effects of using this and other T-cell subset measurements, in the diagnosis of AIDS in two cohorts of homosexual/bisexual men in San Francisco. Among 762 HIV-1 infected men, 200 CD4+ lymphocytes/mm3 corresponded to 13 percent CD4+ lymphocytes and a CD4+/CD8+ ratio of 0.23. If these AIDS-defining criteria had been implemented in mid-1991, the number of living AIDS cases would have increased by 106 (212%), 133 (266%), and 136 (272%), respectively. When these criteria were first met, either before or in the absence of a clinical AIDS diagnosis, about half of the subjects were asymptomatic and the median clinically AIDS-free interval was approximately 2 years. Using two consecutive tests or pair-wise combinations of criteria reduced the number of cases identified by testing error or transient biological variation, but the number of living AIDS cases would still be increased more than twofold. Finally, any AIDS case definition using a specific T-cell subset value will be compromised by the inherent variability in these measurements and the substantial overlap in the results for those with and without clinical manifestations of HIV infection.

To evaluate the distribution of the human immunodeficiency virus type 1 (HIV-1) epidemic among California women, we analyzed HIV-1 seroprevalence and risk factors among women attending sexually transmitted disease (STD) clinics in 21 local health jurisdictions. Using standardized protocols developed by the Centers for Disease Control, we tested unlinked serum specimens from women attending participating STD clinics in 1989. We analyzed demographic characteristics, HIV risk exposure groups, and results of HIV-1 antibody testing on 17,210 specimens with an overall HIV-1 seroprevalence of 0.57%. Seroprevalence rates were highest for African-American women, women 25 to 29 years of age, injection drug users, and women attending STD clinics in San Francisco. After multiple logistic regression analysis, HIV-1 seropositivity remained highest for these four groups. The rate of HIV-1 infection among women attending STD clinics in California underscores the continued need to make HIV counseling and testing an integral component of routine services for women being evaluated for, or presenting with, sexually transmitted diseases.

To assess the prevalence of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) infections among potentially high-risk populations in the city of Tijuana, Mexico, the prevalence of specific antibodies was determined and information on risk behaviors was obtained between June and October 1988. The study involved 631 presumably healthy individuals, randomly selected from a study population recruited sequentially from prisoners, prostitutes, and injecting drug users (IDUs), and randomly from homosexual and bisexual men. The presence of HTLV-1/2 antibodies was determined by enzyme immunoassay and an immunofluorescence method, and positive reactions were confirmed by a radioimmunoprecipitation assay and Western blot. The prevalence of HTLV-1/2 was 2% (2 of 105) among prostitutes, 7% (29 of 410) among prisoners, 1% (1 of 105) among homosexual/bisexual men, and 21% (22 of 106) among IDUs. To properly identify the specific HTLV type, a subsequent sample of 41 imprisoned IDUs were voluntarily and anonymously recruited in June 1990 and asked to donate 20 ml of whole blood. Twenty-two percent (9 of 41) were serologically positive for HTLV-1/2, and polymerase chain reaction analysis performed on peripheral blood mononuclear cells identified HTLV-2 as the specific virus prevalent in this group. Two individuals were positive for human immunodeficiency virus type 1 (HIV-1). One of these individuals was coinfected with HTLV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of blind proficiency testing (PT) to examine analytic performance of human immunodeficiency virus type 1 (HIV-1) antibody testing. A total of 32 hospital, blood bank, public health, and commercial laboratories were included in this study. Test sera were introduced as clinical specimens for HIV-1 testing from private practitioners, group practices, clinics, and hospitals in Southern California. A total of 26 laboratories were located throughout California, with six laboratories located in six other states. Results from 306 enzyme immunoassay screening tests and 192 supplemental tests for HIV-1 were reported. Although one positive specimen was reported as indeterminate in almost 30% of results, screening and supplemental testing performances were excellent, with accuracy levels comparable to performance reported on open PT and performance evaluation surveys in the United States. The indeterminate results were attributed to the interpretive criteria used rather than to laboratory errors. Blind PT can be an important tool in improving the quality of total laboratory testing, the usefulness of laboratory results in patient care, and ultimately the health of the public.

We conducted an unlinked seroprevalence survey for human immunodeficiency virus-type 1 (HIV-1) of 9821 persons who had a routine personal health appraisal examination in 1989 while members of the Kaiser Permanente Medical Care Program in northern California. An outside laboratory performed enzyme immunoassay (EIA) analyses, and the California Viral and Rickettsial Diseases Laboratory confirmed EIA-reactive samples by immunofluorescent assay and Western blot assay. Only 20 specimens (0.2%) were confirmed as positive, and 18 were from men. These data suggest that, at the time of this survey, HIV-1 infection was not widespread in the northern California population represented by this health plan membership.

Study Objective: To determine the seroprevalence rates of hepatitis B virus (HBV) and human T-lymphotropic virus (HTLV-I/II) and to compare these rates with the HIV-1 seroprevalence rate in a sample of injured patients admitted through ten California emergency departments., Design: Prospective blinded testing for serologic markers for HBV, HTLV-I/II, and HIV-1 on routinely collected blood samples., Setting: Ten California hospitals were chosen to reflect geographic and demographic diversity., Type of Participants: All injured adult patients who were admitted to a participating hospital through the ED during consecutive three-month periods from June through November 1989., Measurements: Serum samples were tested for HIV-1 antibody, HTLV-I/II antibody, and hepatitis B surface antigen (HBsAg) using standard methods. Mann-Whitney U tests, chi 2 tests for independence, sign tests, chi 2 tests for goodness of fit, and logistic regression were used as appropriate., Results: Seroprevalence rates were as follows: HBV, 2.6% (57 of 2,209); HTLV-I/II, 2.0% (46 of 2,262); and HIV-1, 1.4% (31 of 2,264)., Conclusion: The seroprevalence rate of HBV was slightly higher than that of HIV-1 in this sample of injured patients. Mortality estimates suggest, however, that HBV and HIV-1 pose roughly similar risks to emergency personnel, although the risk of HBV infection can be markedly reduced by vaccination. The data from this and other studies suggest that the ED incidence of HTLV-I/II in United States is low. The relative health risks to emergency personnel from HTLV-I/II appear to be minimal at this time.

The incidence of acquired immunodeficiency syndrome (AIDS) is increasing among California heterosexuals and children. To assess human immunodeficiency virus (HIV)-1 infection in childbearing women, we conducted a blinded serosurvey of newborns. Dried blood specimens taken from 99% of California births during the third quarter of 1988 (n = 135,808) and linked only to maternal demographic categories were tested for HIV-1 antibody by enzyme immunoassay and confirmed by Western blot. Period prevalence of HIV-1 infection was 7.4 per 10,000 childbearing women. Prevalence was highest for Black women and was also elevated for Hispanic and San Francisco Bay Area women. Findings suggest that California Hispanic women will make up an increasing proportion of new AIDS cases.

A hypothesis is presented in which the immunodeficiency and cell loss leading to acquired immune deficiency syndrome and the clonal deletion associated with immunologic tolerance occur through a common mechanism. In a previous publication we proposed that the interaction of human immunodeficiency virus (HIV) with CD4 delivers activation signals that disrupt immune system regulation. In this article, we compare the biology of HIV infection with recent discoveries concerning the "two-signal" molecular mechanism for thymic selection. We propose that two-signal activation is normally followed by clonal expansion and the programmed death of most or all daughter cells through mechanisms that are proportional to the strength and duration of the activation signals. In the thymus, self-reactive cells are trapped in the continuous presence of both antigen signals (signal 1) and costimulatory signals (signal 2), leading to clonal deletion. In mature lymphocytes, we propose that HIV infection contributes a chronic high-affinity signal 2, which shifts the equilibrium of antigen-activated T-cell populations further toward programmed death. This leads to incremental memory cell deficits and gradual clonal deletion at a rate dependent on the frequency of antigen exposure and the ability of an HIV quasispecies to induce signal 2.

Infection with human immunodeficiency virus (HIV) results in progressive deterioration of the cell-mediated immune system characterized by T-helper-cell dysfunction and loss in the face of signs of generalized immune-system activation. The final stage of HIV disease, AIDS, has a myriad of opportunistic infections and malignancies as its hallmarks. The causal relationship between HIV and this complex disease pattern is clear but the mechanisms by which it occurs are not well understood. There are a number of new developments in our understanding of the natural history of HIV infection from a laboratory standpoint. Our review of this information raises further questions as to the validity of the conventional "cytopathic" model and all its direct descendants. In response to these conflicts, we have developed and present an alternative hypothesis in which AIDS pathogenesis, in all its manifestations, is seen as the outcome of one central process, excess immune activation generated by the interaction of virus with the CD4 receptor. The implications of this hypothesis on therapy of HIV infections are discussed.

Study Objectives: To measure the HIV seroprevalence of injured emergency department patients in a number of California hospitals and to examine the relationship between ED seroprevalence and local AIDS incidence., Design: Prospective blinded testing for HIV-1 antibody was performed on routinely collected blood samples., Setting: Ten California hospitals; group 1 included three hospitals from counties of high AIDS incidence (more than 40 cases per 100,000 population), group 2 included three hospitals from counties of intermediate AIDS incidence (20 to 40 cases per 100,000 population); and group 3 included four hospitals from counties of low AIDS incidence (less than 20 cases per 100,000 population)., Type of Participants: Eligible patients were all adult trauma victims admitted to a participating hospital through the ED during a consecutive three-month period occurring between June and November 1989., Measurements: HIV-1 antibody testing was done using enzyme immunoassay confirmed by immunofluorescence assay. Equivocal results were confirmed by Western blot. Mann-Whitney U test, chi 2 test, and multiple logistic regression were used where appropriate., Results: There were 2,264 patients with adequate blood samples for serologic testing. The seroprevalence rates for hospitals in groups 1, 2, and 3 were significantly different (chi 2 = 8.44, P = .02): Group 1, 2.5% (19 of 756: 95% confidence interval [CI], 1.5% to 3.9%); group 2, 0.9% (10 of 1,078; CI, 0.5% to 1.7%); and group 3, 0.5% (two of 430; CI, 0.06% to 1.7%)., Conclusion: This study suggests that local AIDS incidence rates do not necessarily predict the seroprevalence rates of injured patients who are admitted through local EDs.

The immune response to the p24 core antigen of human immunodeficiency virus type 1 (HIV-1) was studied in serial samples collected prospectively from 52 homosexual males in two separate cohorts from Amsterdam and San Francisco. p24 antibody levels were quantified with an antigen sandwich immunoassay using p24 recombinant antigen as capture and probe. Titers and slopes of dilution curves reflecting antibody affinity were analyzed. Only 45 of 52 men developed a measurable primary immune response to p24. In 17 (33%) patients there was a low response with maximum antibody titer below 66, shallow (low affinity) dilution curve, and 10 of the 17 became HIV antigen positive over a 2 year period. In 24 (46%) of the 52 patients titers ranged from 100-4000, steeper dilution curves were noted, and none became HIV antigen positive. Four (8%) men developed a strong immune response with high titers (greater than 12,000) and high affinity type dilution curve. Over time, after the peak immune response, antibody titer declined in some individuals related in part to the formation of immune complexes between HIV-1 p24 antigen and antibody which were dissociable. In vitro, the addition of increasing amounts of purified p24 antigen corresponded to decreasing antibody titer and a shallower dilution curve suggesting a preferential consumption of high affinity antibodies for complex formation. The magnitude of immune response to HIV-1 p24 antigen varies widely in infected homosexual men. Both the intrinsic ability to mount an immune response and immune complex formation contribute to the measurable antibody level.

The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing. Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory. Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories. The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%. The average specificity was 94.7%, varying between 90.5 and 100%. The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%. Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications. Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples. This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.

A study was conducted to assess the relative contribution of the HIV-1-specific immune response and -nonspecific immune activation to HIV disease progression. The titer of antibody to the p24 core protein and the concentration of serum neopterin were measured in 238 HIV-1-seropositive subjects in a prospective cohort study of homosexual men. Antibody titers were extremely variable among cohort participants but relatively stable over time, suggesting inherent differences in the initial immune response capacity. Neopterin concentrations were also variable at cohort entry but generally increased over time. These two markers, measured at cohort entry, had powerful and independent predictive value for the development of AIDS up to 54 months before diagnosis. Subjects with low antibody titers and high levels of neopterin, had the highest incidence of AIDS (60% over 54 months). Patients with low antibody or high neopterin alone had an intermediate risk (34% incidence) and less than 10% of those with high antibody and low neopterin developed AIDS. We propose that the initial immune response to HIV and virus-mediated immune system activation are independent and innately variable components of an individual's response to HIV infection that interact to determine the clinical outcome.