Search

Background: Human herpesvirus 8 (HHV8), the infectious cause of Kaposi sarcoma, varies dramatically across Africa, suggesting that cofactors correlated with large-area geographic or environmental characteristics may influence risk of infection. Variation in HHV8 seropositivity across small-area regions within countries in Africa is unknown. We investigated this issue in Uganda, where Kaposi sarcoma distribution is uneven and well described.Methods: Archival samples from individuals aged 15-59 years randomly selected from a nationally representative 2004-2005 human immunodeficiency virus-AIDS serobehavioral survey were tested for HHV8 seropositivity with use of enzyme immunoassays based on synthetic peptides from the K8.1 and orf65 viral genes. Adjusted odds ratios and 95% confidence intervals (CIs) of association of HHV8 seropositivity with demographic risk factors were estimated.Results: Among 2681 individuals tested, HHV8 seropositivity was 55.4%. HHV8 seropositivity was lower in female than in male persons (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]) and increased 2.2% (95% CI, 1.0%-3.6%) in female persons and 1.2% (95% CI, 1.0%-2.3%) in male persons per year of age. HHV8 seropositivity was inversely associated with education ( P = .01, for trend) and was elevated in the West Nile region, compared with the Central region (adjusted odds ratio, 1.49 [95% CI, 1.02-2.18]) but not with other regions.Conclusions: Our findings suggest that HHV8 seropositivity in Uganda may be influenced by cofactors correlated with small-area geography, age, sex, and education. [ABSTRACT FROM AUTHOR]

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 99.6% (95% CI; 98.5%, 99.9%), the specificity was 98.8% (95% CI; 98.1%, 99.3%), the positive predictive value was 96.5% (95% CI; 94.5%, 97.8%), and the negative predictive value was 99.9% (95% CI; 99.5%, 100%). It took less than 5 min to perform a single test, and results were returned to clients in less than an hour, during which time clients were counselled. This resulted in a 27% increase in the proportion of clients who learned their serostatus and received counselling. We conclude that simple, rapid HIV tests can be performed accurately on-site within the time frame of a clinic visit, increasing the number of clients who learn their serostatus and receive post-test counselling. [ABSTRACT FROM AUTHOR]

Risk of Kaposi sarcoma (KS) is linked to detection of Kaposi sarcoma-associated herpesvirus (KSHV) DNA in plasma, but little is known about the prevalence and risk factors for plasma KSHV DNA detection among the general population where KS is endemic. Correlates of KSHV plasma detection were investigated in a population-based sample of adult Ugandans (15-59 years) who participated in an HIV/AIDS serobehavioral survey in 2004/2005. KSHV DNA was measured in plasma of 1,080 KSHV seropositive and 356 KSHV seronegative persons using polymerase chain reaction (PCR). KSHV DNA in plasma was detected in 157 (8.7%) persons; of these 149 (95%) were KSHV seropositive and 8 (5%) were seronegative. Detection of KSHV DNA in plasma was significantly associated with male sex (P < 0.001), older age (P = 0.003), residence in a rural versus urban area (P = 0.002), geographic region (P = 0.02), and being KSHV seropositive (13.8% seropositive vs. 2.3% seronegative, P < 0.001). In a multivariable model, KSHV DNA plasma quantity was significantly higher in men (P = 0.002), inversely associated with age (P = 0.05), and residing in an urban area (P = 0.01). In Uganda, KSHV is detected more frequently in the plasma of adult males and residents of rural regions, potentially explaining the increased risk of KS in these subsets of the Ugandan population., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA)., Methods: The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity., Results: Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (ptrend = 0.012) and Socioeconomic components (ptrend = 0.0001), but not with the Sexual-behavioral component (ptrend = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (ptrend = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region., Conclusions: Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally.

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi's sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0-5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients.

Introduction: Sexual transmission of human herpesvirus 8 (HHV8) has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood., Materials and Methods: The study population was a subset of participants (n = 2681) from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software., Results: The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend)<0.0001). In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97) and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08), and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89). HHV8 seropositivity was not associated with HIV (P = 0.660) or with herpes simplex virus 2 (P = 0.732) seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity., Conclusion: Our findings are compatible with the conclusion that sexual transmission of HHV8 in Uganda, if it occurs, is weak.

Background: Infant immunization against hepatitis B began in Uganda in 2002., Objective: To determine the baseline prevalence of hepatitis B virus (HBV) infection and explore risk factors., Methods: A hepatitis B prevalence study was nested in the 2005 national HIV/AIDS serobehavioural survey. Demographic characteristics and risk factors were explored by questionnaire. One third of blood specimens (n=5875) from adults aged 15 to 59 years were tested for hepatitis B core antibodies (HBcAb); positive specimens were tested for hepatitis B surface antigen (HBsAg)., Results: HBcAb was present in 52.3% (95% CI: 51.0-53.6) of adults, and HBsAg in 10.3% (9.5-11.1). By 15-19 years of age, 40.0% had been infected with HBV. Prevalence of both markers was significantly higher across northern Uganda, in rural areas, among the poor and least educated, and in uncircumcised men. Other independent predictors of infection were age, ethnic group, occupation, number of sex partners, and HIV and HSV-2 status., Conclusion: Hepatitis B virus infection is highly endemic in Uganda, with transmission occurring in childhood and adulthood. More than 1.4 million adults are chronically infected and some communities disproportionately affected. The hepatitis B infant immunization programme should be sustained and catch-up vaccination considered for older children.

Objective: HIV programs in generalized epidemics have traditionally relied on antenatal clinic (ANC) sentinel surveillance data to guide prevention and to model epidemic trends. ANC data, however, come from a subset of the population, and their representativeness of the population has been debated., Methods: Data from a national population-based Uganda HIV/AIDS Sero-Behavioral Survey (UHSBS) were compared with those from ANC sentinel surveillance. Using geographic information system, UHSBS clusters within a 30 km radius of the ANC sites were mapped. Estimates of HIV prevalence from ANC surveillance were compared with those from UHSBS., Results: The ANC-based HIV prevalence, 6.0% [confidence interval (CI) 5.5% to 6.5%], was similar to that from UHSBS, 5.9% (CI 5.4% to 6.4%). The ANC-based estimate correlated with that of UHSBS catchment area women who were pregnant and those who had given birth in the 2 years preceding the survey. ANC data overestimated prevalence in the 15-year to 19-year age group, were similar to UHSBS for ages 20-29 years, and underestimated prevalence in older respondents. ANC data underestimated HIV prevalence among women (6.0% vs. 7.4%; CI 6.6% to 8.2%) and urban women (7.6% vs. 12.7%) but was similar for rural women (5.3% vs. 4.9%)., Conclusions: ANC-based surveillance remains an important tool for monitoring HIV/AIDS programs. ANC and UHSBS data were similar overall and for 15-year to 29-year olds, women who were pregnant, and women who had a birth in the 2 years before the survey. ANC estimates were lower in those > or = 30 years and in urban areas. Periodic serosurveys to adjust ANC-based estimates are needed.

Introduction: Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether peripheral blood viral load is a marker of KS burden (total number of KS lesions), KS progression (the rate of eruption of new KS lesions), or both is unclear. We investigated these relationships in persons with AIDS., Methods: Newly diagnosed patients with AIDS-related KS attending Mulago Hospital, in Kampala, Uganda, were assessed for KS burden and progression by questionnaire and medical examination. Venous blood samples were taken for HHV8 load measurements by PCR. Associations were examined with odds ratio (OR) and 95% confidence intervals (CI) from logistic regression models and with t-tests., Results: Among 74 patients (59% men), median age was 34.5 years (interquartile range [IQR], 28.5-41). HHV8 DNA was detected in 93% and quantified in 77% patients. Median virus load was 3.8 logs10/10(6) peripheral blood cells (IQR 3.4-5.0) and was higher in men than women (4.4 vs. 3.8 logs; p=0.04), in patients with faster (>20 lesions per year) than slower rate of KS lesion eruption (4.5 vs. 3.6 logs; p<0.001), and higher, but not significantly, among patients with more (>median 20 KS lesions) than fewer KS lesions (4.4 vs. 4.0 logs; p=0.16). HHV8 load was unrelated to CD4 lymphocyte count (p=0.23)., Conclusions: We show significant association of HHV8 load in peripheral blood with rate of eruption of KS lesions, but not with total lesion count. Our results suggest that viral load increases concurrently with development of new KS lesions.

To monitor the relative prevalence and evolutionary trends of HIV-1 in Uganda, we conducted a retrospective study of pregnant women over the time period 1989-2000. From a total of 300 women sampled, we defined subtypes by heteroduplex mobility assay for 230 subjects and by partial sequencing and phylogenetic analyses of the env gene for 216 subjects. Subtypes A and D were most prevalent, and there were no significant trends in relative frequencies of subtypes A (45%), D (41%), C (5%), or recombinants (9%) over the 11 years sampled. There was also no phylogenetic clustering of subtypes related to geography (clinic location) or year of collection. Mean pairwise nucleotide diversity of subtype A (pi = 0.163) and subtype D (pi =0.156) samples did not differ significantly between subtypes, nor did these levels change over the period of the study. This report suggests that among pregnant women in Uganda A and D subtypes are transmitted without geographic constraints, and are not associated with significantly different transmission rates.

Kaposi sarcoma (KS) occurs with relatively high frequency in immunosuppressed transplant recipients and in patients with AIDS. Recently, Italian investigators reported transplant-related KS tumors bearing donor-derived antigens, suggesting possible parenteral transmission of KS as whole cells, i.e., chimeric tumors. To investigate the hypothesis that KS whole cells may also be transmitted into immunocompromised persons via heterosexual acts, we tested nodular KS lesions and matched normal tissue obtained from female patients with AIDS for the presence of the Y-chromosome specific sex determining sequence (SRY). Among 25 unique tumors tested, none was positive for SRY sequence. While our results do not exclude sexual cellular transmission of whole KS cells, they suggest that if it occurs, it is rare.

This study aims at estimating the recent trends in HIV-1 prevalence and the factors associated with infection among pregnant women in the Gulu District of north Uganda, a rural area severely affected by civil strife. In 2000-2003, a total of 4459 antenatal clinic attendees of Lacor Hospital were anonymously tested for HIV-1 infection. The overall and age-specific prevalence did not show any significant trend over time. The age-standardized prevalence slightly declined, from 12.1% in 2000 to 11.3% in 2003. Increased age [20-24 years: adjusted odds ratio (AOR) 1.63; 95% CI 1.18-2.25; >or=25 years: AOR 2.56; 95% CI 1.91-3.44], residence in urban areas (AOR 1.76; 95% CI 1.41-2.18), being unmarried (AOR 1.60; 95% CI 1.27-2.01), increased age of partner (25-34 years: AOR 1.87; 95% CI 1.29-2.73; >or=35 years: AOR 2.68; 95% CI 1.72-4.16), modern occupation of partner (AOR 1.98; 95% CI 1.53-2.58), and short time of residence at the current address (AOR 1.36; 95% CI 1.05-1.76) were associated with infection. The HIV-1 prevalence in this rural district is high and similar to that observed in urban antenatal clinics, probably reflecting the effect of the last 18 years of civil strife.

Objective: To determine whether data from voluntary counseling and testing (VCT)/prevention of mother-to-child transmission (PMTCT) programs can be used for HIV surveillance., Methods: Women attending an antenatal clinic at the district hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered counseling and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided for HIV-positive women and their babies. Those who declined VCT were tested for HIV anonymously., Results: Overall, 2635 women accepted VCT; 883 were tested anonymously. HIV prevalence was higher in VCT than in anonymously tested women in the first month of the program (20% vs. 11%, P=0.05) and in months with <70% VCT uptake (17% vs. 8%, P<0.001) but was similar in months with high uptake. Uptake of VCT was higher in women who had risk factors for HIV, especially those who believed themselves to have been exposed (84% vs. 73%, P<0.001)., Conclusion: There was a bias to accepting VCT in women with HIV, or risk factors for HIV infection, the former most apparent when there was low coverage. Data from VCT/PMTCT programs cannot replace anonymous surveillance for monitoring of HIV epidemic trends where coverage is incomplete within clinics or communities.