Chikungunya and O'nyong-nyong Viruses in Uganda: Implications for Diagnostics.

Background: A serosurvey of healthy blood donors provided evidence of hemorrhagic fever and arthropod-borne virus infections in Uganda.

Methods: Antibody prevalence to arthropod-borne and hemorrhagic fever viruses in human sera was determined using enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT).

Results: The greatest antibody prevalence determined by ELISA was to chikungunya virus (CHIKV) followed in descending order by West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Ebola virus (EBOV), dengue virus (DEN), yellow fever virus (YFV), Rift Valley fever virus (RVFV), Marburg virus (MARV), and Lassa virus (LASV).

Sex and Urbanicity Contribute to Variation in Lymphocyte Distribution across Ugandan Populations.

Management of patient care and interpretation of research data require evaluation of laboratory results in the context of reference data from populations with known health status to adequately diagnose disease or make a physiological assessment. Few studies have addressed the diversity of lymphocyte subsets in rural and urban Ugandan populations. Here, 663 healthy blood bank donors from semi-urban centers of Kampala consented to participate in a study to define lymphocyte reference ranges.

Reference intervals in healthy adult Ugandan blood donors and their impact on conducting international vaccine trials.

Background: Clinical trials are increasingly being conducted internationally. In order to ensure enrollment of healthy participants and proper safety evaluation of vaccine candidates, established reference intervals for clinical tests are required in the target population.

Methodology/principal Findings: We report a reference range study conducted in Ugandan adult blood bank donors establishing reference intervals for hematology and clinical chemistry parameters.

Large-scale human immunodeficiency virus rapid test evaluation in a low-prevalence ugandan blood bank population.

The use of rapid tests for human immunodeficiency virus (HIV) has become standard in HIV testing algorithms employed in resource-limited settings. We report an extensive HIV rapid test validation study conducted among Ugandan blood bank donors at low risk for HIV infection. The operational characteristics of four readily available commercial HIV rapid test kits were first determined with 940 donor samples and were used to select a serial testing algorithm.

Transmission of human herpesvirus 8 by blood transfusion.

Background: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic.

Methods: We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001.

Prevalence and screening costs of hepatitis C virus among Ugandan blood donors.

Background: Screening donated blood for hepatitis C virus (HCV) is important for HCV prevention and is routinely practiced in North America and Europe. However, in many African countries little is known about HCV prevalence or cost-effectiveness of HCV antibody (anti-HCV) screening.

Methods: We investigated 2592 plasma specimens collected consecutively from blood donors in central Uganda in 1999.

Kaposi's sarcoma in Uganda: risk factors for human herpesvirus 8 infection among blood donors.

Human herpesvirus 8 (HHV-8) is etiologically linked to Kaposi's sarcoma, a common cancer in Uganda. The authors assessed HHV-8 seroprevalence, risk factors for infection, and HHV-8 assays in a cross-sectional study of Ugandan blood donors. Of 3,736 specimens, the authors selected 203 reactive for HIV, hepatitis B surface antigen (HBsAg), or syphilis, and, randomly, 203 nonreactive specimens.

Phase I/II trial of HIV-1 hyperimmune globulin for the prevention of HIV-1 vertical transmission in Uganda.

Objectives: To assess the safety, tolerance, pharmacokinetics, and virologic and immunologic changes associated with the use of Ugandan HIV hyperimmune globulin (HIVIGLOB) in HIV infected pregnant Ugandan women and their infants.

Design: A prospective, phase I/II, three-arm dose escalation trial of HIVIGLOB.

Methods: HIVIGLOB was prepared from discarded HIV infected units of blood collected from the National Blood Bank in Kampala.

HIV-1 ICD p24 antigen detection in ugandan infants: use in early diagnosis of infection and as a marker of disease progression.

The objective of this study was to determine the use of immune-complex dissociated (ICD) p24 antigen detection for the diagnosis and prognosis of HIV-1 infection in Ugandan children. Plasma collected prospectively from children born to HIV-1 infected Ugandan women was stored and later analyzed for the presence of neutralizable HIV-1 p24 antigen using the Coulter ICD p24 antigen and neutralization kits. HIV-1 infection status, disease progression, and survival of the children were determined.

Identification of diverse HIV type 1 subtypes and dual HIV type 1 infection in pregnant Ugandan women.

Vertical (mother-to-child) transmission accounts for the majority of pediatric HIV-1 infections. Many factors are involved in vertical transmission, however it is not clear which factors are most important for determining whether a mother will transmit HIV-1 to her infant. It has been suggested that HIV-1 subtype may influence vertical transmission and that subtype D viruses may be less likely to be transmitted in this setting.

Analysis of HIV type 1 protease and reverse transcriptase in antiretroviral drug-naive Ugandan adults.

We analyzed plasma HIV-1 from 27 antiretroviral drug-naive Ugandan adults. Previous subtype analysis of env and gag sequences from these samples identified subtypes A, C, D, and recombinant HIV-1. Sequences of HIV-1 protease and reverse transcriptase (RT) were obtained with a commercial HIV-1 genotyping system.

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients.

Rapid HIV testing with same-day results: a field trial in Uganda.

Rapid, on-site HIV testing with same-day results may improve services and increase the number of clients who learn their serostatus in developing countries. To validate test performance under field conditions and assess the change in the proportion of clients who learn their serostatus, we conducted a field trial using the Capillus HIV-1/HIV-2 assay (Cambridge Diagnostics) at the AIDS Information Centre counselling and testing sites in Uganda. Compared to the standard 2-EIA testing algorithm, the sensitivity of Capillus was 99.

Serologic and phylogenetic characterization of HIV-1 subtypes in Uganda.

Objectives: To determine the HIV genetic subtypes present in HIV-1-infected asymptomatic blood donors in Uganda and to evaluate serologic detection of infection by commercial immunoassays; to evaluate samples for HIV-1 group O infections.

Methods: Sixty-four HIV-seropositive plasma samples were collected from the Nakasero Blood Bank, Kampala, Uganda. The plasma were evaluated using commercial HIV enzyme immunoassays (EIA) and a research immunoblot.

Detection of human immunodeficiency virus type 1 (HIV-1) DNA and RNA sequences in HIV-1 antibody-positive blood donors in Uganda by the Roche AMPLICOR assay.

The ability of commercially available PCR-based assays to accurately detect or quantitate human immunodeficiency virus type 1 (HIV-1) DNA or RNA in individuals predominantly infected with HIV-1 subtypes A and D is not known. Therefore, peripheral leukocytes from 43 individuals in Kampala, Uganda, positive for HIV by the Western blot (immunoblot) assay were tested by using the Roche AMPLICOR HIV-1 assay for the detection of DNA gag sequences. Plasma from these same individuals was tested by using the Roche HIV-1 AMPLICOR MONITOR HIV-1 assay for the quantitation of HIV-1 RNA gag sequences.

Comparison of saliva and serum for human immunodeficiency virus type 1 antibody testing in Uganda using a rapid recombinant assay.

The accuracy and acceptability of saliva human immunodeficiency virus type 1 (HIV-1) antibody testing were compared with serum testing in a study of paired specimens from HIV-1-seropositive and HIV-1-seronegative Ugandan adults attending a clinic for sexually transmitted diseases. Saliva collection was performed with the Omni-sal device (Saliva Diagnostic Systems, Vancouver, Wash.), and antibody testing was performed by a rapid filter paper assay (Test-Pack; Abbott Laboratories, Abbott Park, Ill.

Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission.

Objective: To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk, the duration of breastfeeding, and vertical transmission of HIV-1 infection in Ugandan women.

Methods: A prospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1-seropositive and 86 HIV-1-seronegative Ugandan women approximately 6 weeks after delivery.

Maternal HIV-1 RNA serum levels at delivery and vertical transmission in Uganda.

Objective: To evaluate the clinical utility of maternal HIV-1 RNA serum levels at delivery in predicting the rate of HIV-1 vertical transmission.

Design And Methods: HIV-1 RNA levels were determined by the Roche Amplicor Monitor assay in serum specimens collected at the time of delivery from 94 transmitting and 107 nontransmitting infected mothers and 12 seronegative mothers in Uganda. Nonparametric Wilcoxon-Rank sum tests were used to identify significant differences in medians and RNA level distributions by transmission status.

Relative reactivity of the V3 loop PND of HIV-1 subtypes A, B, C, D, and F with sera from selected Ugandan localities.

Synthetic peptides comprising the predicted principal neutralizing determinant (PND) in new African and North American HIV-1 clones were tested in ELISA for reactivity with ninety six serum samples from asymptomatic donors in six selected localities in Uganda. Irrespective of the geographical origin of the samples, the majority of the test sera cross-reacted at high intensities with the peptides derived from the North American clone, BRT3.6 (Group B), the Ugandan clone, CUG045, (Group C), and the Romanian clone, FRMA (Group F).

Lack of association between anti-V3 loop antibodies and perinatal transmission of HIV-1 in Kampala, Uganda.

This study evaluated the association between reactivity of maternal antibody to human immunodeficiency virus type 1 (HIV-1) V3 loop peptides and perinatal transmission in Uganda. Plasma from 40 HIV-1-infected mothers (20 transmitting and 20 nontransmitting mothers) and 31 uninfected mothers in Uganda were tested for reactivity and antibody titer to synthetic peptides representing V3 loop sequences from HIV-1 strains MN, SF2, LAI, ZR6, and CM235 and consensus peptides CA, CB, and CD. No significant differences were found between 20 transmitting mothers and 20 nontransmitting mothers in terms of percent reactivity or titer of antibody to any of the V3 loop peptides tested.

Peptide serology for analysis of the inter- and intra-individual variation in the HIV-1 V3 domain.

Objective: To investigate whether the specificity of antibody responses to the gp120 V3 domain in HIV-1-infected individuals is related to the variability of this region.

Methods: Sera from a cohort of 22 HIV-1-infected Ugandans were tested against peptides derived from each individual's autologous proviral V3 apex sequence. Autologous peptide reactivity was compared with reactivity to peptides derived from two Ugandan consensus sequences and previously isolated US/European and African viruses.

A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

Objective: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers.

Design: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer.

Setting: University research hospitals in both the United States and Africa.