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The influence of host factors (tobacco use, dentition, bleeding gums, oral rinsing, nasal medications, and time since the last meal) on immunoglobulin G (IgG) concentration in oral fluids (OF) was determined by univariate and multivariate analysis. Significant differences in IgG concentration were found to be associated with human immunodeficiency virus (HIV) status (HIV antibody positive, +16.60 μg/ml, P = 0.0001), sex (female, +1.23 μg/ml, P = 0.004), dentition (+2.83 μg/ml, edentulous versus dentulous, P = 0.0001), bleeding gums (+6.35 μg/ml, P = 0.0001), and time since the last meal (+3.55 μg/ml, >6 h, P = 0.0001). These factors could impact diagnostic methods that rely on the immunoglobulin concentration in OF specimens.

Research has demonstrated that oral mucosal transudate (OMT), a serum-derived fluid that enters saliva from the gingival crevice and across oral mucosal surfaces, can be preferentially concentrated by a novel collecting system to yield detectable levels of immunoglobulins (i.e., IgG and IgM antibodies) against various bacterial and viral diseases. Assays based on OMT can aid in the diagnosis of disease and in the management of therapeutic drugs. A reliable and accurate OMT-based test to detect human immunodeficiency virus (HIV) antibodies is commercially available. Additional tests based on similar technologies may aid in the diagnosis of viral hepatitis, measles, mumps, and rubella as well as in monitoring levels of therapeutic drugs such as theophylline. The future use of OMT-based testing will likely increase because of the inherent advantages of this technology: convenience; avoidance of inadvertent transmission of blood-borne pathogens; ease of use in pediatric and geriatric populations; as well as the potential for blood-free home and workplace collection of patient samples.

Serologic reactivities of serum or plasma from 55 HIV-1 subjects in four countries—Brazil, Rwanda, Thailand, and Uganda—were examined by V3 peptide immunoassay. Forty-seven (85.5%) of the 55 specimens tested positive to the homologous peptide. A strong correlation between serotype (i.e., pattern of serologic reactivity with a panel of peptides) and genotype was not found. However, the V3 peptide immunoassays may be useful for epidemiologic studies to trace the distinctive HIV-1 strains from different geographic regions of the world. The serology data obtained may be useful for the development of effective V3-based vaccines.

Simian immunodeficiency viruses (SIVs) are primate lentiviruses that are morphologically similar and biologically related to human immunodeficiency viruses (HIVs)1–4. SIVs naturally infect some nonhuman primate species, such as African green monkeys and sooty mangabey monkeys, without causing immunodeficiency. In contrast, experimental SIV infection of other susceptible primate species, such as macaques, can cause chronic wasting syndromes and a disease similar to the human acquired immunodeficiency syndrome (AIDS)5–10. Because of the similarities between the human and nonhuman lentiviruses, SIV and its susceptible primate host have become the principal model for studying the pathogenesis of AIDS and developing . . .

A simplified human immunodeficiency virus 1 (HIV-1)-specific IgA capture enzyme immunoassay (IgA-CEIA) was evaluated and compared with IgA-Western blot assay for early diagnosis of HIV-1 infection in infants born to seropositive women. A total of 232 coded sera collected prospectively from 70 infants were tested. All 25 sera from 10 HIV-1-negative infants born to seronegative mothers (negative controls) were negative by both assays. All 111 sera from 37 seroreverting, uninfected infants were negative by IgA-CEIA (specificity, 100%), whereas 110 of 111 sera were negative by IgA-Western blot assay (specificity, > 99%). Overall IgA-CEIA detected HIV-IgA in 20 (87%) of 23 infected infants, and IgA-Western blot assay detected HIV-IgA in 21 (91.3%) of 23 infants; specimen-wise agreement between the 2 assays was > 80%. Analysis of results by age group indicated that after 2 months of age both assays were equivalent with sensitivity ranging from 60 to 80%. Quantitative data provided by IgA-CEIA suggests that the bulk of HIV-1 IgA synthesis in most HIV-1-infected infants occurs after 2 months of age.

We have developed a combination immunoblot (combi-blot) for simultaneous detection and differentiation of HIV-1 and HIV-2 antibodies using HIV-1 lysate and HIV-1 and HIV-2 synthetic peptide antigens in a single assay. Minimal modification in antigen strip preparation and no modification in assay procedure of the current HIV-1 Western blot protocol was required. Implementation of this combi-blot following the use of the combination HIV-1/-2 enzyme immunoassay would simplify the current HIV testing algorithm and increase the accuracy of HIV-2 surveillance.

The testing of neonatal blood specimens dried on filter paper for maternal HIV antibodies, using an enzyme immunoassay (EIA) with confirmation of repeatedly reactive specimens by immunoblot (IB), was first described in 1987. It has been used to conduct large, unlinked, anonymous HIV seroprevalence surveys for surveillance of HIV in child-bearing women in several countries. We directly assessed the sensitivity and specificity of this combination of tests to detect maternal HIV antibodies.Serum samples obtained from mothers delivering at a major hospital in Kinshasa, Zaire were screened for HIV antibody using the rapid assay HIVCHEK.Plasma from HIVCHEK-positive women and age-matched negative controls were tested by enzyme-linked immunosorbent assay (ELISA); repeatedly reactive specimens were confirmed by Western blot (WB). Two days after delivery, whole blood was obtained from each newborn by heel-stick, dried on filter paper, and tested by EIA. Repeatedly reactive specimens were confirmed by IB.The serologic status of neonatal filter-paper specimens was compared with that of corresponding maternal plasma.The testing of neonatal filter-paper specimens using EIA, with confirmatory testing of repeatedly reactive specimens using IB, was 100.0% sensitive [of the 192 ELISA-positive and WB-positive maternal plasma specimens, 192 of the corresponding newborn filter-paper specimens were EIA-positive and IB-positive; 95% confidence interval (CI), 98.1-100]. The detection of maternal HIV antibodies was 99.6% specific using this combination of tests (of the 281 ELISA-negative or ELISA-positive but WB-negative maternal plasma samples, 280 of the corresponding newborn filter-paper specimens were EIA-negative or EIA-positive but IB-negative; 95% CI, 98.0-100).Maternal HIV antibodies can be detected accurately by testing neonatal blood dried on filter paper, using EIA with confirmation of repeatedly reactive specimens by IB. This approach can facilitate the determination of HIV seroprevalence in child-bearing women in countries with neonatal screening programs, or where serum or plasma is difficult to obtain.Neonatal blood specimens dried on filter paper have been tested for maternal HIV antibodies in large, unlinked, anonymous HIV seroprevalence surveys toward the surveillance of HIV in child-bearing women in several countries. This study assesses the sensitivity and specificity of this combination of tests. The standard approach involves first testing the sample via an enzyme immunoassay (EIA), then confirming repeatedly reactive specimens through immunoblot (IB). To test this methodology, serum samples were obtained from mothers delivering at a major hospital in Kinshasa, Zaire, and screened with rapid assay HIVCHEK for antibody to HIV. Plasma from HIVCHEK-positive women and age-matched negative controls were then subjected to ELISA, with repeatedly reactive samples confirmed with Western blot. Whole blood was later obtained by heel-stick from each newborn 2 days after delivery, dried on filter paper, and tested by EIA and IB for confirmation. The serologic statuses of neonatal filter-paper specimens were then compared with those of corresponding maternal plasma. 100% sensitivity was achieved by testing neonatal filter-paper specimens with EIA and confirming with IB. The combination of tests also proved 99.6% specific for detecting maternal HIV antibodies; both results are at 95% confidence intervals. These results demonstrate that maternal HIV antibodies can therefore be detected accurately by testing neonatal blood dried on filter paper, using EIA, then confirming repeatedly reactive specimens via IB. This approach may help determine HIV seroprevalence in childbearing women in countries with neonatal screening programs or where serum or plasma is difficult to obtain.

Human immunodeficiency virus (HIV) infection, regardless of clinical stage, produces many biologic indicators of virus infection, replication, or both (Fig. 5.1). Such indicators include viremia, antibodies against viral proteins, circulating viral proteins, and nonspecific markers of infection such as neopterin, 32-microglobulins, and changes in the absolute number of and the ratio of CD4 and CD8 cells. Most of the markers can be detected and in many cases semiquantified by serologic tests (Table 5.1). These tests have been used to protect the blood supply, diagnose infections, monitor the progression of disease, monitor the efficacy of drug therapy, and diagnose infections in infants born to HIV-infected mothers. The availability of highly specific, inexpensive tests for HIV antibody, such as the enzyme immunoassay (EIA), have permitted public health agencies to conduct-large scale seroprevalence surveys to define the epidemic.

In the HIV Seroprevalence Survey among Childbearing Women (SCBW), antibodies to human immunodeficiency virus type 1 are detected using enzyme immunoassays (EIA) and Western blot (WB) methods modified to accommodate samples of blood dried on special collection paper. Dried blood spot (DBS) eluates positive by EIA are tested by one of two WB methods, the miniblot technique using equipment from Immunetics Corporation and the PBS Integra assay (pageblot) from Genetic Systems. In this report we compared the performance of the two WB methods. The identity and position of the viral proteins on the WB were identified using monoclonal antibodies and monospecific antisera. The blots differed substantially in their composition and concentration of viral glycoproteins. Performance of the WB assays with DBS elution buffers from different EIA kits was equivalent except for samples eluted in the Abbott buffer, which reduced detection of antibodies to the p31, p51, p55, and p66 viral proteins. Case classification of DBS, positive sera, dilution curve samples, and seroconversion panels was equivalent by both tests in the presence of all elution buffers. Proficiency evaluation panels sent to SCBW participating laboratories over a 3-year period were used to note the differences between the two WB methods in detection of antibodies to the viral glycoproteins.

The development and subsequent licensure by the U.S. Food and Drug Administration (FDA) of enzyme immunoassays (EIA) for human immunodeficrency virus (HIV) antibody provided a low-cost test that was well suited for diagnosis, mass screening of populations, and testing blood donations for HIV infection. Each year the number of tests performed as well as the number of laboratories performing tests increases in the United States, but programs for quality control (QC) of laboratory testing have not kept pace. Standard panels of serum for quality control and evaluation of EIA and western blot tests are not generally available. Quality control programs for serologic tests are crude compared to the sophisticated computer-driven programs used in clinical chemistry laboratories. In fact, some serology laboratories do no more than run the controls supplied by the kit manufacturer. Some serology laboratories, however, have adapted the QC procedures similar in design to those used for clinical chemistry to monitor testing for HIV infections. This chapter will describe these adaptations and recommend a simple and inexpensive system for quality control of HIV tests.

Persons infected with the human immunodeficiency virus (HIV) have a spectrum of clinical features, ranging from persons who are infected but appear completely healthy to those with rapid disease progression and mortality. All groups, regardless of clinical stage, possess several biologic indicators of viral infection or replication (Figure 5.1). These include viremia, antibodies against viral proteins, circulating viral proteins, and nonspecific markers such as neopterin, beta2-microglobulins, and T4 cell counts. A variety of immunologic tests currently exists for the detection of viral antibodies and protein antigens. These assays have permitted testing programs to protect the blood supply from infected units and to conduct seroprevalence surveys to define the epidemic. More recently, the presence or absence of viral and nonspecific markers have been used to predict the onset of clinical disease.

To identify cost-effective testing strategies for HIV-1 and HIV-2 infections, we evaluated different combinations of tests on serum specimens from 1134 consecutive patients attending tuberculosis treatment centers in Abidjan, Cote d'Ivoire. Virus-specific whole-virus enzyme-linked immunosorbent assay (WVE), Western blot (WB) and synthetic peptide enzyme-linked immunosorbent assay (SPE) were used in sequential fashion to determine the true prevalence of infection; 27% were reactive to HIV-1, 5% to HIV-2, and 10% to both viruses. Of 239 specimens positive on WB for both HIV-1 and HIV-2, SPE diagnosed 38% as HIV-1-reactive and 16% as HIV-2-reactive, while 46% remained reactive to both viruses. Using WVE or one of two rapid (5–10 min) mixed (HIV-1 and HIV-2) antigen tests (RMATs) as a screening test, followed by SPE as a supplemental test, gave results with sensitivity of 97.3–99.2%, specificity of 99.5–99.7%, and positive predictive value for diagnosing HIV infection of 99.4–99.6%, with important savings in time and reagent costs. SPE allows more specific distinction between HIV-1 and HIV-2 infections than WB, and could replace it as a supplemental test in many settings. WB may be required for specimens reactive on screening tests but negative on SPE, until sensitivity of the SPE is further evaluated. A mixed antigen screening test followed by SPE seems to be an efficient testing strategy for diagnosing HIV-1 and HIV-2 infections.

In Reply. —We agree with Dr Ryder's conclusion that "a positive EIA and indeterminate Western blot may be merely a false alarm." Oral mucosal transudate and blood HIV testing are subject to outcomes that are uncertain and require follow-up testing to arrive at a definitive result. When indeterminate HIV test results are interpreted by experts, inferences about true HIV status may be drawn from the magnitude of the EIA test signal and from the nature (viral vs nonviral) of individual Western blot bands. Thus, the tone of the message during counseling might differ depending on whether the test result is likely to be a false alarm or is distinctly worrisome. The predictive value of the "EIA component" of HIV testing may be of academic interest, but the clinically relevant factor is the full testing algorithm. Oral mucosal transudate testing never resulted in a false-positive outcome. Just as with blood, there are occasional

Objective. —To determine accuracy of a human immunodeficiency virus type 1 (HIV-1) antibody testing system using a device to collect and stabilize oral mucosal transudate (OMT), a fluid with increased levels of IgG; an enzyme immunoassay (EIA) screening test optimized for OMT; and a Western blot confirmatory test designed for use with OMT. Design. —The OMT specimens were tested by EIA and, if indicated, confirmatory Western blot according to a standard testing algorithm. The OMT results were compared with true HIV status as determined by serum testing and/or clinical diagnosis. Patients. —Specimens from 3570 subjects (2382 at low risk, 698 at high risk, 242 with acquired immunodeficiency syndrome [AIDS], and 248 "nonspecificity" [persons with diseases associated with an increased frequency of false-positive results in HIV testing]) were collected at 11 geographically diverse sites (including blood banks, public health clinics, general medical clinics, HIV clinics, sexually transmitted disease clinics, and a hemophilia center) in the United States. Main Outcome Measures. —Overall accuracy of testing OMT for HIV-1 antibodies compared with true HIV-1 antibody status; sensitivity and specificity of OMT EIA and Western blot. Results. —Sensitivity of OMT EIA testing in 673 true-positive subjects was 99.9% (672/673). The OMT Western blot results in the 673 true-positive subjects were positive in 665 and indeterminate in 8. The EIA followed by Western blot (if EIA was repeatedly reactive) yielded a negative result in 99.9% (2893/2897) of OMT samples from true negatives and an indeterminate result in 4. The OMT testing system provided the correct result or would trigger appropriate follow-up testing in 3569 (>99.9%) of 3570 cases. Conclusion. —HIV-1 antibody testing of OMT samples is a highly accurate alternative to serum testing.

Objective. —To compare mother-to-child transmission of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) and to assess the impact of maternal HIV-1 and HIV-2 infections on child survival. Design. —Prospective cohort study. Setting. —Maternal and child health center in a lower socioeconomic class district of Abidjan, Ivory Coast. Participants. —A total of 18 099 women delivering between 1990 and 1992 were tested for HIV-1 and HIV-2 antibodies. A cohort of 613 pregnant women and their infants was followed prospectively (138 women reactive to HIV-1,132 reactive to HIV-2, 69 reactive to both viruses, and 274 HIV-seronegative). Main Outcome Measures.—Rates of perinatal transmission for HIV-1, HIV-2, and both viruses, determined from results of serological and polymerase chain reaction tests on children; survival of infants born to HIV-1—positive, HIV-2—positive, dually reactive, and HIV-seronegative women. Results. —Of the 18 099 women tested, 9.4% were reactive to HIV-1 alone, 1.6% to HIV-2 alone, and 1.0% to both viruses. The rate of perinatal transmission of HIV-1 was 24.7% (95% confidence interval [CI], 15.8% to 33.7%), compared with 1.2% (95% CI, 0.0% to 3.5%) for HIV-2 (relative risk, 21.3; 95% CI, 2.9 to 154.3). Overall, 19.0% (95% CI, 9.0% to 29.0%) of infants of dually reactive women became infected; of the 11 children concerned, 10 were infected with HIV-1 and one with HIV-1 and HIV-2. Infants of HIV-seropositive mothers had a reduced survival; mortality rates were 15.1, 13.0, 6.5, and 3.4 deaths per 100 child-years, respectively, for children of HIV-1—positive, dually reactive, HIV-2—positive, and HIV-seronegative women. Conclusions. —The rate of perinatal transmission of HIV-2 (1.2%) was much lower than the rate of perinatal transmission of HIV-1 (24.7%), and this was associated with more favorable survival for infants of HIV-2—infected mothers. Dually reactive women could transmit both viruses, although transmission usually involved HIV-1 only. Public health guidelines should incorporate advice that perinatal transmission of HIV-2 is rare. ( JAMA . 1994;272:462-466)

WITHIN the past year, the US Food and Drug Administration (FDA) has licensed two combined human immunodeficiency virus type 1 (HIV-1)/human immunodeficiency virus type 2 (HIV-2) enzyme immunoassays (EIAs) for screening donated blood and plasma. The FDA has also mandated that by June 1, 1992, US blood centers must implement testing for antibodies to HIV-2 in addition to testing for antibodies to HIV-1. Implementation of this policy and reports of HIV-2—infected US residents have raised important public health and clinical questions about HIV-2 infection in the United States. This article summarizes current information regarding the epidemiology and diagnosis of HIV-2 infection and discusses public health considerations that arise from the presence of HIV-2 in the United States. BACKGROUND: WORLDWIDE DISTRIBUTION, TRANSMISSION, AND NATURAL HISTORY Infection with HIV-2 is endemic in many countries in West Africa, but generally much rarer elsewhere in the world. 1,2 The highest prevalence of HIV-2 infection

A national, population-based survey was initiated in 1988 to measure the prevalence of human immunodeficiency virus (HIV) infection in women giving birth to infants in the United States. Following standardized procedures, residual dried-blood specimens collected on filter paper for newborn metabolic screening were tested anonymously in state public health laboratories for maternal antibody to HIV. As of September 1990, annual survey data were available from 38 states and the District of Columbia. The highest HIV seroprevalence rates were observed in New York (5.8 per 1000), the District of Columbia (5.5 per 1000), New Jersey (4.9 per 1000), and Florida (4.5 per 1000). Nationwide, an estimated 1.5 per 1000 women giving birth to infants in 1989 were infected with HIV. Assuming a perinatal transmission rate of 30%, we estimate that approximately 1800 newborns acquired HIV infection during one 12-month period. Preventing transmission of HIV infection to women and infants is an urgent public health priority. (JAMA. 1991;265:1704-1708)

A comparative study was made of the single radial immunodiffusion test and the classical quantitative precipitin test for determining the amount of precipitable antibodies present in streptococcal groups A and C antisera. The potency of 21 group A and 54 group C antisera was determined by both methods; purified group-specific carbohydrates were used as antigens. The coefficient of correlation between the results from the two methods was 0.976 for group A antisera and 0.946 for group C antisera. When the concentration of antigen, the volume of antiserum used, and the depth of the antigen-agar mixture are kept constant, the diameter of the precipitin disc is directly related to the concentration of precipitable antibodies present in the antiserum. The use of the radial immunodiffusion test for evaluating and standardizing streptococcal grouping antisera is discussed as well as the advantages and disadvantages of using a concentrated vaccine for producing these antisera.

To determine risk factors for HIV infection among abandoned Romanian infants and children living in a public institution.A cross-sectional study was conducted in June 1990 among 101 children between 0 and 4 years of age living in an orphanage. Orphanage and hospital records were reviewed and a blood specimen for hepatitis B and HIV serologic testing obtained from each child. A case-control study was conducted using data from the cross-sectional study. Cases were HIV-positive children; one HIV-negative control, matched by age, was selected for each case.Overall, 20 (20%) children were HIV-positive, 88 (87%) tested positive for antibody to hepatitis B core antigen, and 32 (32%) were hepatitis B surface antigen-positive. In the case-control study, HIV-positive children had received more therapeutic injections [mean, 280; median, 231] than age-matched HIV-negative children [mean; 142, median, 155; P = 0.02]. Cases were more likely than controls to have received over 200 lifetime injections (odds ratio, 5.7; 95% confidence interval, 1.2-32.7). Blood transfusions and mother-to-child transmission were excluded as routes of HIV transmission. By reviewing sterilization records and interviewing local health-care workers, we determined that needles and syringes were often re-used without proper disinfection in the orphanage.These data provide strong epidemiologic evidence that indiscriminate injections with contaminated needles and syringes were responsible for HIV transmission in this population.