T J Spira

National Health Laboratory Service, Johannesburg, Gauteng, South Africa

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Publications (135)1799.36 Total impact

  • Thomas J Spira, Tedd V Ellerbrock
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2012; 59(5):e82-4. DOI:10.1097/QAI.0b013e31824c1985 · 4.39 Impact Factor
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    ABSTRACT: Estimation of HIV-1 incidence is an important public health tool for understanding the status of the epidemic, identifying high-risk populations, and assessing various intervention strategies. Several laboratory-based methods have been developed for distinguishing recent from long-term HIV-1 infection; however, each exhibits some degree of misclassification, particularly among AIDS patients and those taking antiretroviral therapy (ART). To improve upon the limitations associated with measuring responses to a single analyte, we have developed a bead-based, multiplex assay for determination of HIV recent infection based on total antibody binding and antibody avidity to multiple analytes. An HIV-specific, multiplex panel was created by coupling the recombinant HIV-1 proteins p66, gp120, gp160, and gp41 to Bio-Plex COOH microspheres. Longitudinal plasma specimens from recent seroconverters were tested for reactivity to the coupled microspheres using the Bio-Plex 200 System. For each analyte, HIV-specific antibody binding and avidity increased for 1-2 years post-seroconversion, leading to a significant difference in reactivity between recent and long-term specimens. While the potential for misclassification of individuals diagnosed with AIDS or receiving ART appears to be minimal with avidity measures, the impact on total antibody binding was variable, depending on the individual analyte. This bead-based, HIV-specific multiplex assay measures several distinct immune responses in a single assay plate, allowing for sampling of multiple analytes in the determination of recent infection, which could aid in the development of improved statistical methods or algorithms that will more accurately estimate HIV incidence.
    AIDS research and human retroviruses 06/2011; 28(2):188-97. DOI:10.1089/AID.2011.0037 · 2.46 Impact Factor
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    ABSTRACT: Quality assurance (QA) is a systematic process to monitor and improve clinical laboratory practices. The fundamental components of a laboratory QA program include providing a functional and safe laboratory environment, trained and competent personnel, maintained equipment, adequate supplies and reagents, testing of appropriate specimens, internal monitoring of quality, accurate reporting, and external quality assessments. These components are necessary to provide accurate and precise CD4 T-cell counts, an essential test to evaluate start of and monitor effectiveness of antiretroviral therapy for HIV-infected patients. In recent years, CD4 testing has expanded dramatically in resource-limited settings. Information on a CD4 QA program as described in this article will provide guidelines not only for clinical laboratory staff but also for managers of programs responsible for supporting CD4 testing. All agencies involved in implementing CD4 testing must understand the needs of the laboratory and provide advocacy, guidance, and financial support to established CD4 testing sites and programs. This article describes and explains the procedures that must be put in place to provide reliable CD4 determinations in a variety of settings.
    American Journal of Clinical Pathology 10/2010; 134(4):556-67. DOI:10.1309/AJCPP7MCHFYLX2FM · 3.01 Impact Factor
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    ABSTRACT: The expansion of HIV/AIDS care and treatment in resource-constrained countries, especially in sub-Saharan Africa, has generally developed in a top-down manner. Further expansion will involve primary health centers where human and other resources are limited. This article describes the World Health Organization/President's Emergency Plan for AIDS Relief collaboration formed to help scale up HIV services in primary health centers in high-prevalence, resource-constrained settings. It reviews the contents of the Operations Manual developed, with emphasis on the Laboratory Services chapter, which discusses essential laboratory services, both at the center and the district hospital level, laboratory safety, laboratory testing, specimen transport, how to set up a laboratory, human resources, equipment maintenance, training materials, and references. The chapter provides specific information on essential tests and generic job aids for them. It also includes annexes containing a list of laboratory supplies for the health center and sample forms.
    American Journal of Clinical Pathology 07/2009; 131(6):887-94. DOI:10.1309/AJCPRID8CQY5THES · 3.01 Impact Factor
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    Nature Reviews Microbiology 11/2008; 6(11 Suppl):S29-38. DOI:10.1038/nrmicro2000 · 23.32 Impact Factor
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    ABSTRACT: Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.
    Journal of clinical microbiology 06/2008; 46(5):1588-95. DOI:10.1128/JCM.02196-07 · 4.23 Impact Factor
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    ABSTRACT: The global HIV/AIDS pandemic and guidelines for initiating anti-retroviral therapy (ART) and opportunistic infection prophylaxis demand affordable, reliable, and accurate CD4 testing. A simple innovative approach applicable to existing technology that has been successfully applied in resource-challenged settings, PanLeukogated CD4 (PLG), could offer solutions for cost saving and improved precision. Day-old whole blood from 99 HIV+ donors was simultaneously studied in five North-American laboratories to compare the performance of their predicate methods with the dual-platform PLG method. The predicate technology included varying 4-color CD45/CD3/CD4/CD8 protocols on different flow cytometers. Each laboratory also assayed eight replicate specimens of day-old blood from 10 to 14 local donors. Bias and precision of predicate and PLG methods was studied between- and within-participating laboratories. Significantly (P < 0.0001) improved between-laboratory precision/coefficient of variation (CV%) was noted using the PLG method (overall median 9.3% vs. predicate median CV 13.1%). Within-laboratory precision was also significantly (P < 0.0001) better overall using PLG (median 4.6% vs. predicate median CV 6.2%) and in 3 of the 5 laboratories. PLG counts tended to be 11% smaller than predicate methods (P < 0.0001) for shipped (median of predicate-PLG = 31) and local specimens (median of predicate-PLG = 23), both overall and in 4 of 5 laboratories (median decreases of 4, 16, 20, and 21% in shipped specimens); the other laboratory had a median increase of 5%. Laboratories using predicate CD4 methods similar to those in this study could improve their between-laboratory and their within-laboratory precision, and reduce costs, by switching to the PLG method after adequate training, if a change (usually, a decrease) in CD4 counts is acceptable to their health systems.
    Cytometry Part B Clinical Cytometry 01/2008; 74 Suppl 1(S1):S52-64. DOI:10.1002/cyto.b.20417 · 2.28 Impact Factor
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    ABSTRACT: Persons occupationally exposed to nonhuman primates (NHPs) can be persistently infected with simian foamy virus (SFV). The clinical significance and person-to-person transmissibility of zoonotic SFV infection is unclear. Seven SFV-infected men responded to annual structured interviews and provided whole blood, oral, and urogenital specimens for study. Wives were tested for SFV infection. Proviral DNA was consistently detected by PCR in PBMCs of infected men and inconsistently in oral or urogenital samples. SFV was infrequently cultured from their PBMCs and throat swabs. Despite this and a long period of intimate exposure (median 20 years), wives were SFV negative. Most participants reported nonspecific symptoms and diseases common to aging. However, one of two persons with mild thrombocytopenia had clinically asymptomatic nonprogressive, monoclonal natural killer cell lymphocytosis of unclear relationship to SFV. All participants worked with NHPs before 1988 using mucocutaneous protection inconsistently; 57% described percutaneous injuries involving the infecting NHP species. SFV likely transmits to humans through both percutaneous and mucocutaneous exposures to NHP body fluids. Limited follow-up has not identified SFV-associated illness and secondary transmission among humans.
    AIDS Research and Human Retroviruses 12/2007; 23(11):1330-7. DOI:10.1089/aid.2007.0104 · 2.46 Impact Factor
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    ABSTRACT: We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8). Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies. The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid. We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.
    AIDS 08/2007; 21(12):1541-5. DOI:10.1097/QAD.0b013e3282202b7d · 6.56 Impact Factor
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    ABSTRACT: The success of antiretroviral therapy is known to be compromised by drug-resistant HIV-1 at frequencies detectable by conventional bulk sequencing. Currently, there is a need to assess the clinical consequences of low-frequency drug resistant variants occurring below the detection limit of conventional genotyping. Sensitive detection of drug-resistant subpopulations, however, requires simple and practical methods for routine testing. We developed highly-sensitive and simple real-time PCR assays for nine key drug resistance mutations and show that these tests overcome substantial sequence heterogeneity in HIV-1 clinical specimens. We specifically used early wildtype virus samples from the pre-antiretroviral drug era to measure background reactivity and were able to define highly-specific screening cut-offs that are up to 67-fold more sensitive than conventional genotyping. We also demonstrate that sequencing the mutation-specific PCR products provided a direct and novel strategy to further detect and link associated resistance mutations, allowing easy identification of multi-drug-resistant variants. Resistance mutation associations revealed in mutation-specific amplicon sequences were verified by clonal sequencing. Combined, sensitive real-time PCR testing and mutation-specific amplicon sequencing provides a powerful and simple approach that allows for improved detection and evaluation of HIV-1 drug resistance mutations.
    PLoS ONE 02/2007; 2(7):e638. DOI:10.1371/journal.pone.0000638 · 3.53 Impact Factor
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    ABSTRACT: To examine trends in HIV prevalence in the US household population, serum or urine samples from 2 National Health and Nutrition Examinations Surveys (NHANES) (1988-1994 and 1999-2002), were tested for HIV antibody. In the 1999 to 2002 survey, data on risk behaviors, CD4 T lymphocytes, and antiretroviral therapy (ART) were also available. In the 1988 to 1994 survey, there were 59 positive individuals of 11,203 tested. In NHANES 1999 to 2002, there were 32 positive individuals of 5926 tested. The prevalence of HIV infection among those aged 18 to 39 years in NHANES 1988 to 1994 was 0.38% (95% confidence interval [CI]: 0.22-0.68) as compared with 0.37% (95% CI: 0.17 to 0.80) in 1999 to 2002. Prevalence did not change significantly between surveys in any race and/or ethnic or gender group among 18- to 39-year-old participants. HIV prevalence was 3.58% (95% CI: 1.88 to 6.71) among non-Hispanic blacks in the 40- to 49-year-old age group in 1999 to 2002, but the age range available in NHANES 1988 to 1994 was 18 to 59 years and does not allow direct comparison of prevalence. Cocaine use and the presence of herpes simplex virus-2 antibody were the only significant risk factors for HIV infection for non-Hispanic blacks. Fifty-eight percent of infected individuals not reporting ART had CD4 T-lymphocyte counts < 200 cells/mm3 compared with 18.2% on therapy and 12.5% of participants newly informed of their HIV status.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2006; 41(5):651-6. DOI:10.1097/01.qai.0000194235.31078.f6 · 4.39 Impact Factor
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    ABSTRACT: Use of the standard dual-platform flow cytometric method for determination of CD4(+) T-lymphocyte counts, which needs both a flow cytometer (FCM) and hematological analyzer, would inevitably lead to increased variability. The development of new single-platform (SP) FCMs that provide direct CD4(+) T-lymphocyte counts for improved assay precision and accuracy have recently attracted attention. This study evaluated one of those systems, CyFlow(green) (Partec), a single-parameter SP volumetric FCM. The performance of CyFlow(green) was compared with those of two reference standard SP microbead-based technologies of the three-color TruCOUNT tube with the FACScan FCM and a two-color FACSCount system (Becton Dickinson Biosciences). Absolute CD4(+) and CD8(+) T-lymphocyte counts in 200 human immunodeficiency virus type 1-seropositive blood specimens were determined. Statistical analysis for correlation and agreement were performed. A high correlation of absolute CD4 counts was shown when those obtained with CyFlow(green) were compared with those obtained with the bead-based three-color TruCOUNT system (R(2)=0.96; mean bias, -69.1 cells/microl; 95% confidence interval [CI], -225.7 to+87.5 cells/microl) and the FACSCount system (R(2)=0.97; mean bias, -40.0 cells/microl; 95% CI, -165.1 to+85.1 cells/microl). The correlation of the CD4(+) T-lymphocyte counts obtained by the two bead-based systems was high (R(2)=0.98). Interestingly, CyFlow(green) yielded CD4(+) T-lymphocyte counts that were 21.8 and 7.2 cells/microl lower than those obtained with the TruCOUNT and the FACSCount systems, respectively, when CD4(+) T-lymphocyte counts were <250 CD4(+) T-lymphocyte counts/microl range or 17.3 and 5.8 cells/microl less, respectively, when CD4(+) T-lymphocyte counts were <200 cells/microl. The single-parameter CyFlow(green) volumetric technology performed well in comparison with the performance of the standard SP bead-based FCM system. However, a multicenter comparative study is needed before this FCM machine is implemented in resource-limited settings.
    Clinical and Diagnostic Laboratory Immunology 01/2006; 12(12):1416-24. DOI:10.1128/CDLI.12.12.1416-1424.2005 · 2.51 Impact Factor
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    ABSTRACT: The combination of unique single nucleotide polymorphisms in the CCR5 regulatory and in the CCR2 and CCR5 coding regions, defined nine CCR5 human haplogroups (HH): HHA-HHE, HHF*1, HHF*2, HHG*1, and HHG*2. Here we examined the distribution of CCR5 HH and their association with HIV infection and disease progression in 36 HIV-seronegative and 76 HIV-seropositive whites from North America and Spain [28 rapid progressors (RP) and 48 slow progressors (SP)]. Although analyses revealed that HHE frequencies were similar between HIV-seronegative and HIV-seropositive groups (25.0% vs. 32.2%, p > 0.05), HHE frequency in RP was significantly higher than that in SP (48.2% vs. 22.9%, p = 0.002). Survival analysis also showed that HHE heterozygous and homozygous were associated with an accelerated CD4 cell count decline to less than 200 cells/microL (adjusted RH 2.44, p = 0.045; adjusted RH = 3.12, p = 0.037, respectively). These data provide further evidence that CCR5 human haplogroups influence HIV-1 disease progression in HIV-infected persons.
    AIDS Research and Human Retroviruses 03/2005; 21(2):111-5. DOI:10.1089/aid.2005.21.111 · 2.46 Impact Factor
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    ABSTRACT: To address whether human herpesvirus 8 (HHV-8) DNA in peripheral blood mononuclear cells (PBMCs) might be the product of latent or lytic infection and to shed light on sporadic detection of HHV-8 DNA in individuals seropositive for the virus, we studied the frequency of infected cells, total virus load, and virus load per infected cell in PBMCs from men coinfected with HHV-8 and human immunodeficiency virus (HIV), some of whom had Kaposi's sarcoma. The low frequencies of infected cells detected (fewer than one per million cells in some individuals) suggest that the prevalence of the virus in circulating leukocytes was underestimated in previous studies that employed more conventional sampling methods (single, small-volume specimens). Mean virus loads ranged from 3 to 330 copies per infected PBMC; these numbers can represent much higher loads in individual lytically infected cells (>10(3) genomes/cell) in mixtures that consist predominantly of latently (relatively few genomes) infected cells. The presence in some subjects of high HHV-8 mean genome copy numbers per infected cell, together with viral DNA being found in plasma only from subjects with positive PBMCs, supports earlier suggestions that the virus can actively replicate in PBMCs. In some individuals, mean virus loads were less than 10 genomes per infected cell, suggesting a tightly controlled purely latent state. HHV-8 genome copy numbers are substantially higher in latently infected cells derived from primary effusion lymphomas; thus, it appears that HHV-8 is able to adopt more than one latency program, perhaps analogous to the several types of Epstein-Barr virus latency.
    Journal of Virology 12/2004; 78(21):11707-14. DOI:10.1128/JVI.78.21.11707-11714.2004 · 4.65 Impact Factor
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    ABSTRACT: Although the introduction of HAART decreased substantially the incidence of Kaposi's sarcoma (KS), KS remains the most common cancer among individuals infected with human immunodeficiency virus (HIV). To define markers for progression to KS from the asymptomatic infection of human herpesvirus 8 (HHV-8), serologic responses against HHV-8 were compared between KS-negative and -positive men who were seropositive for both HIV and HHV-8. There was no difference in prevalence of detectable neutralizing antibodies between the two groups. The prevalence of anti-ORF73 antibodies among the dual seropositive patients increased in proportion to their risk of KS. In specimens obtained from 11 HIV+ patients at different intervals over a period of 4-12 years, increase of anti-ORF73 antibody titers was observed in the patients who developed KS but not in the patients who did not develop KS. These results suggest that there is a difference in serologic response against ORF73 between the HIV patients with and without KS.
    Journal of Medical Virology 10/2004; 74(2):202-6. DOI:10.1002/jmv.20167 · 2.22 Impact Factor
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    ABSTRACT: To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men. Longitudinal study of 87 HHV-8- and HIV-seropositive men [42 with Kaposi's sarcoma (KS)] during four visits over a 2 month period. : Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA. HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22]. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51). Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.
    AIDS 10/2004; 18(13):1819-26. DOI:10.1097/00002030-200409030-00011 · 6.56 Impact Factor
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    ABSTRACT: Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV-8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV-8 by children in low seroprevalence areas. Antibody screening was carried out for HHV-8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS-endemic area (Nigeria). For children in the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%). However, US children aged 6 months to 5 years had higher HHV-8 antibody titers than did 6-17-year-old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross-reactivity between assays for HHV-8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV-8 transmission among children where HHV-8 is not endemic occurs, but is uncommon. The findings also suggest that HHV-8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues.
    Journal of Medical Virology 01/2004; 72(1):126-31. DOI:10.1002/jmv.10548 · 2.22 Impact Factor
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    ABSTRACT: Primary immunodeficiency (PI) diseases are a group of primarily single-gene disorders of the immune system. Approximately 100 separate PI diseases have been described, but <20 probably account for >90% of cases. Although diverse, PI diseases share the common feature of susceptibility to infection and result in substantial morbidity and shortened life spans. Most important, prompt diagnosis and treatment can now lead to life-saving treatment and result in marked improvements in the quality and length of life for persons with PI diseases. In November 2001, a workshop was convened by CDC in Atlanta, Georgia, to discuss ways to improve health outcomes among persons with PI disease. A multidisciplinary panel of persons knowledgeable in PI diseases and public health met to identify and discuss public health strategies that can be applied to PI diseases and possibly for other genetic disorders. A systematic assessment based on the established public health framework was applied to the growing group of PI diseases, whose diverse genetic mutations span multiple components of the immune system but all lead to increased incidence and severity of infections. During the meeting, specialists in clinical immunology, public health, genetics, pediatrics, health communication, and ethics from state and federal agencies, academic centers, professional organizations, and advocacy foundations discussed the four components of the public health framework as they relate to PI diseases. These four components include 1) public health assessment (application of traditional public health methods to assess the occurrence and impact of PI diseases on communities); 2) population-based interventions (development, implementation, and evaluation of screening tests administered to newborns and clinical algorithms for early recognition of symptomatic persons to facilitate the earliest possible diagnosis and treatment for PI diseases); 3) evaluation of screening and diagnostic tools (to ensure their quality and appropriateness for identification of patients with PI diseases); and 4) communication (communication with and information dissemination to health-care providers and the public to facilitate prompt and appropriate diagnosis and intervention). The working group's deliberations focused on challenges and opportunities, priority research questions, and recommendations for future action for these four components. These recommendations, developed by workshop participants, will be useful to medical and public health professionals who are evaluating methods to increase recognition of PI diseases and other genetic disorders.
    MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control 01/2004; 53(RR-1):1-29.
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    ABSTRACT: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV. Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS. Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed. Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9-39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5-3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4-14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0-10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2-78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0-1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0-1.6) or oral fluids (OR, undefined; = 0.001). In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.
    AIDS 02/2003; 17(2):215-22. DOI:10.1097/01.aids.0000042943.55529.48 · 6.56 Impact Factor
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    ABSTRACT: Specific mutations in VPR and V2 potentially restrict HIV-1 replication in macrophages. Such restriction could potentially limit HIV replication in long-term non-progressors (LTNP), thus accounting for low viral load and delayed progression to AIDS. To examine whether a specific VPR phenotype (truncated versus non-truncated) correlates with disease progression and whether elongated V2 restricts viral replication in macrophages or alters viral tropism. Sequence analysis was carried for VPR and V1-V3 env from four rapid progressors (RPs), six late progressors (LPs), and three LTNPs in cohort of HIV-1-infected homosexual men. The replication kinetics of sequential isolates was examined in primary CD4 cells and macrophages and coreceptor usage was determined by GHOST infection assays. No differences were found in the VPR protein from RP and LTNP isolates. Analysis of the V2 region revealed that all RPs maintained similar V2 lengths (40 aa), whereas LPs and LTNPs acquired additional amino acids (2-13 aa) in the V2 region. Coreceptor specificity revealed that RP switch from CCR5 to multiple coreceptor usage, whereas LTNPs maintained R5 viruses. Sequential isolates from each group revealed comparable replication efficiencies in both T-cells and macrophages, regardless of the V2 length or coreceptor utilization. In addition, cross-section analysis of six LTNPs from Australia revealed extended V2 with consistent usage of CCR5 coreceptor. The present results suggest that acquisition of a V2 extension over time in HIV-1-infected LPs/LTNPs appears to correlate with maintenance of CCR5 usage among LTNPs. These findings may be important for a better understanding of the host interactions and disease progression.
    AIDS 10/2002; 16(14):1887-98. DOI:10.1097/00002030-200209270-00005 · 6.56 Impact Factor

Publication Stats

5k Citations
1,799.36 Total Impact Points


  • 2008
    • National Health Laboratory Service
      Johannesburg, Gauteng, South Africa
  • 2002
    • STD Med, Inc.
      Stoughton, Massachusetts, United States
  • 1983–2002
    • Centers for Disease Control and Prevention
      • • National Center for Emerging and Zoonotic Infectious Diseases
      • • Division of Viral Diseases
      Druid Hills, GA, United States
  • 1999
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
  • 1998
    • National Institute of Allergy and Infectious Diseases
      베서스다, Maryland, United States
    • Bar Ilan University
      Gan, Tel Aviv, Israel
  • 1993–1994
    • Emory University
      • • Department of Pediatrics
      • • Division of Infectious Diseases
      Atlanta, GA, United States
  • 1989
    • U.S. Department of Health and Human Services
      Washington, Washington, D.C., United States
  • 1983–1989
    • University of Innsbruck
      • Institut für Biochemie
      Innsbruck, Tyrol, Austria
  • 1987–1988
    • Beth Israel Medical Center
      • Department of Medicine
      New York City, NY, United States
  • 1986
    • Abbott Laboratories
      North Chicago, Illinois, United States
  • 1985
    • Zoo Atlanta
      Atlanta, Georgia, United States
  • 1984
    • University of New Mexico
      • Division of Hospital Medicine
      Albuquerque, New Mexico, United States