Donor-derived Kaposi's sarcoma in a liver-kidney transplant recipient.

Human herpes virus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver-kidney transplant. The donor had multiple risk factors for HHV-8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)-positive persons seeking organ transplantation and serving as organ donors for HIV-positive recipients, HHV-8 prevalence among donors and recipients will likely increase and with that the risk for post-transplant KS. Predetermination of HHV-8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV-8 antibody screening.

Varicella zoster virus in American Samoa: seroprevalence and predictive value of varicella disease history in elementary and college students.

The epidemiology of varicella is believed to differ between temperate and tropical countries. We conducted a varicella seroprevalence study in elementary and college students in the US territory of American Samoa before introduction of a routine varicella vaccination programme. Sera from 515 elementary and 208 college students were tested for the presence of varicella-zoster virus (VZV) IgG antibodies. VZV seroprevalence increased with age from 76·0% in the 4-6 years group to 97·7% in those aged ⩾23 years. Reported history of varicella disease for elementary students was significantly associated with VZV seropositivity. The positive and negative predictive values of varicella disease history were 93·4% and 36·4%, respectively, in elementary students and 97·6% and 3·0%, respectively, in college students. VZV seroprevalence in this Pacific island appears to be similar to that in temperate countries and suggests endemic VZV circulation.

Molecular epidemiology of varicella zoster virus.

Varicella zoster virus has highly conserved genome 125,000 base pairs. The different molecular genetic methods of analyzing VZV genome are discussed, as well as their results with regards to the virus phylogenesis, geographic distributions, possible recombination and virulence of different VZV strains.

Genomic analysis of varicella-zoster virus: primers for individual open reading frames.

The genome of varicella-zoster virus (VZV) contains nearly 125,000 bp. Preliminary genomic analysis has revealed that VZV may be less immutable than once thought. Through the investigation of the VZV genome using specifically designed oligonucleotides, it has been learned that sequence variation within VZV open reading frame 62 can distinguish between vaccine and wild-type virus. Additionally, the presence of single nucleotide polymorphisms within the VZV genome has identified distinct VZV populations originating from circumscribed geographic locations. In order for future studies of VZV genetic diversity to be carried out, amplifying and sequencing primers for individual VZV genes have been catalogued. Additionally, this report will facilitate the selection of VZV primers by which to distinguish clinical VZV isolates from vaccinia virus isolates.

Rapid genotyping of varicella-zoster virus vaccine and wild-type strains with fluorophore-labeled hybridization probes.

We developed a single-tube rapid method for the detection and differentiation of varicella-zoster virus (VZV) vaccine and wild-type strains that combines rapid-cycle PCR with wild-type-specific fluorescent probe melting profiles for product genotyping. A region including the polymorphic site in VZV open reading frame (ORF) 62 was amplified in the presence of two fluorescence-labeled hybridization probes. During the annealing step of the thermal cycling, both probes bound to their complementary sequences in the amplicon, resulting in resonance energy transfer, thus providing real-time fluorescence monitoring of PCR. Continuous acquisition of fluorescence data during a melting curve analysis at the completion of PCR revealed that loss of fluorescence occurred in a strain-specific manner as the detection probe, which was fully complementary to the wild-type VZV ORF 62 region, melted off the template. Use of this method allowed genotyping of samples within minutes after the completion of PCR, eliminating the need for post-PCR sample manipulation. In addition to reducing the time required to produce a result, this method substantially reduces the risk of contamination of the final product as well as the risk of sample tracking errors. The genotypes of 79 VZV-positive samples determined by this fluorescent resonance energy transfer (FRET) method were identical to the genotypes obtained by conventional PCR and restriction fragment length polymorphism analysis. The genotyping of VZV strains by the FRET method is a rapid and reliable method that is suitable for typing and that is also practical for use for the processing of large numbers of specimens.

Improved identification and differentiation of varicella-zoster virus (VZV) wild-type strains and an attenuated varicella vaccine strain using a VZV open reading frame 62-based PCR.

A new method was developed to identify and differentiate varicella-zoster virus (VZV) wild-type strains from the attenuated varicella Oka vaccine strain. The PCR technique was used to amplify a VZV open reading frame (ORF) 62 region. A single specific amplicon of 268 bp was obtained from 71 VZV clinical isolates and several laboratory strains. Subsequent digestion of the VZV ORF 62 amplicons with SmaI enabled accurate strain differentiation (three SmaI sites were present in amplicons of vaccine strain VZV, compared with two enzyme cleavage sites for all other VZV strains tested). This method accurately differentiated the Oka vaccine strain from wild-type VZV strains circulating in countries representing all six populated continents. Moreover, the assay more reliably distinguished wild-type Japanese strains from the vaccine strain than did previously described methods.

HIV-1 and other sexually transmitted infections in a cohort of female sex workers in Chiang Rai, Thailand.

OBJECTIVES: To determine demographic and behavioural factors and sexually transmitted infections (STIs) associated with prevalent HIV-1 infection among brothel based and other female sex workers (FSWs) in Chiang Rai, northern Thailand. METHODS: Data were collected from questionnaires, physical examinations, and laboratory evaluations on Thai FSWs enrolled in a prospective cohort study in Chiang Rai, Thailand, from 1991 to the end of 1994. RESULTS: HIV-1 seroprevalence was 32% among 500 women: 47% for 280 brothel workers and 13% for 220 other FSWs (p < 0.001); 96% of infections were due to HIV-1 subtype E. At enrolment, other STIs were common: chlamydia, 20%; gonorrhoea, 15%; active syphilis (serological diagnosis), 9%; genital ulcer, 12%; seroreactivity to Haemophilus ducreyi, 21%, and herpes simplex virus type 2 (HSV-2), 76%. On multiple logistic regression analysis, HIV-1 was associated with brothel work, birth in upper northern Thailand, initiation of commercial sex at < 15 years of age, syphilis, HSV-2 seropositivity, and genital ulcer. CONCLUSIONS: Young Thai FSWs working in brothels in northern Thailand in the early phase of the HIV epidemic have been at very high risk for HIV-1 infection and several other STIs. Programmes are needed to prevent girls and young women from entering the sex industry and to reduce the risk of infection with HIV-1 and other STIs.

Analysis of herpes simplex virus 1 and 2 infection in women with high risk sexual behaviour in Mexico.

BACKGROUND: This paper describes the seroprevalence and risk factors of Herpes simplex virus (HSV) infection in a group of female prostitutes from Mexico City. METHODS: Women who consented to participate in the study voluntarily attended a sexually transmitted disease (STD) clinic during 1992. A standardized questionnaire was administered and a blood sample was obtained from each participant. Type-specific Western blot serology was performed to determine the serostatus of HSV-1 and HSV-2 for participants. Bivariate and multivariate analyses were applied to identify variables associated with an increased risk for HSV infection. RESULTS: Prevalences of infection among the 997 prostitutes studied were 93.9% for HSV-1 and 60.8% for HSV-2. Only 1.8% of the women were seronegative for both viruses. The only variable associated with HSV-1 seropositivity was crowding index. The following variables were associated with an increased risk for infection with HSV-2: age, level of education, working site, born outside Mexico City and increasing time as a prostitute. CONCLUSIONS: This is the first assessment of HSV infection in Mexico and may be useful for the development and application of control and preventive measures among the prostitute population at risk of acquiring and transmitting human immunodeficiency virus (HIV) and other STD.

Herpes in the time of AIDS: a comparison of the epidemiology of HIV-1 and HSV-2 in young men in northern Thailand.

OBJECTIVES: To compare the epidemiologic pattern of HIV-1, a recently introduced sexually transmitted disease (STD) agent in Thailand, with the pattern of HSV-2, a well-established STD agent, so that future trends for both viruses can be better understood. METHODS: We obtained questionnaire data and determined HSV-2 (by specific gG-2) and HIV-1 seroreactivity in a cohort of 1,115 young male army conscripts who entered service in northern Thailand in 1991. RESULTS: Seroprevalence of HIV-1 and HSV-2 was 6.9% and 14.9%, respectively. For HSV-2-seropositive men who reported previous genital ulcers, HIV-1 seroprevalence was 32%. For most variables, there was a close correspondence between the prevalence ratios for HIV-1 and for HSV-2, except that prevalence ratios for HIV-1 tended to be greater than the corresponding ratios for HSV-2. The seroprevalence of both viruses was strongly related to early and frequent contact with female sex workers (FSWs), infrequent use of condoms with FSWs, and residence in the upper north region of Thailand. When differences in sexual behavior between the upper north and lower north were controlled for, the seroprevalence of both viruses still differed significantly by region. CONCLUSIONS: Although the seroprevalence levels of HSV-2 and HIV-1 were quite different in this cohort of Thai army conscripts in 1991, the patterns of infection in terms of demographic, residential, and behavioral variables were similar. Seroprevalence studies of HSV-2 in other populations, particularly where the HIV-1 epidemic is just beginning, may be useful in predicting which subgroups might be most vulnerable to the epidemic and could therefore benefit the most from public health intervention. Where differences in the patterns of the two viruses have been noted, we hypothesize that the pattern for HIV-1 will evolve toward that seen for HSV-2.

PIP: Herpes simplex virus type 2 (HSV-2) has been in Thailand longer than has been HIV-1. The epidemiology of the 2 viruses was compared in an attempt to gain insight into likely future trends of the dissemination of HIV-1 and HSV-2 in the country. Findings are based upon questionnaire and serostatus data on a cohort of 1115 young male army conscripts who entered service in northern Thailand in 1991. The 1061 conscripts were 21 years old and the remainder were 22-27 years old. 879 were unmarried, 598 were farmers, and 55 were students. 6.9% of the young men were infected with HIV-1 and 14.9% with HSV-2. Among HSV-2-seropositive men who reported previous genital ulcers, HIV-1 seroprevalence was 32%. For most variables, there was a close correspondence between the prevalence ratios for HIV-1 and HSV-2, except that prevalence ratios for HIV-1 tended to be greater than the corresponding ratios for HSV-2. The seroprevalence of both viruses was strongly related to early and frequent contact with female prostitutes, infrequent condom use with such prostitutes, and residence in the upper northern region of Thailand. The patterns of infection were similar for the 2 viruses, suggesting the direction in which HIV-1 seroprevalence levels will go.

Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2.

Type-specific serologic assays for herpes simplex virus (HSV) types 1 and 2 based on glycoprotein G-1 (gG-1) (HSV-1) and gG-2 (HSV-2) discriminate between antibodies against HSV-1 and HSV-2. We previously developed a Western blot assay using gG-1 and gG-2 expressed in baculovirus, performed extensive validation studies, and determined that it was both sensitive and specific for type-specific detection of HSV antibody. Here we report that, among a cohort of Thai military recruits, the serostatus of some individuals changed from positive to negative over time (6.6% among those ever positive for HSV-1, and 14.9% among those ever positive for HSV-2). We tested a subset of these specimens in three other gG-based assays: an enzyme-linked immunosorbent assay, an immunoblot strip assay, and a Western blot assay. Positive-to-negative shifts occurred in every assay; the frequency of the shifts ranged from 6. 1% to 21.2% of the specimen sets tested. There was only limited agreement among the assays concerning which individuals lost reactivity. This inaccuracy, exhibited by all of the assay protocols, was not predicted by validation studies employing specimens from cross-sectional studies and was most pronounced in HSV-2 testing. This argues for the inclusion of serial blood specimens in serologic assay validation procedures.

Surveillance for chronic fatigue syndrome--four U.S. cities, September 1989 through August 1993.

PROBLEM/CONDITION: Although chronic fatigue syndrome (CFS) has been recognized as a cause of morbidity in the United States, the etiology of CFS is unknown. In addition, information is incomplete concerning the clinical spectrum and prevalence of CFS in the United States. REPORTING PERIOD COVERED: This report summarizes CFS surveillance data collected in four U.S. cities from September 1989 through August 1993. DESCRIPTION OF SYSTEM: A physician-based surveillance system for CFS was established in four U.S. metropolitan areas: Atlanta, Georgia; Wichita, Kansas; Grand Rapids, Michigan; and Reno, Nevada. The objectives of this surveillance system were to collect descriptive epidemiologic information from patients who had unexplained chronic fatigue, estimate the prevalence and incidence of CFS in defined populations, and describe the clinical course of CFS. Patients aged > or = 18 years who had had unexplained, debilitating fatigue or chronic unwellness for at least 6 months were referred by their physicians to a designated health professional(s) in their area. Those patients who participated in the surveillance system a) were interviewed by the health professional(s); b) completed a self-administered questionnaire that included their demographic information, medical history, and responses to the Beck Depression Inventory, the Diagnostic Interview Schedule, and the Sickness Impact Profile; c) submitted blood and urine samples for laboratory testing; and d) agreed to a review of their medical records. On the basis of this information, patients were assigned to one of four groups: those whose illnesses met the criteria of the 1988 CFS case definition (Group I); those whose fatigue or symptoms did not meet the criteria for CFS (Group II); those who had had an identifiable psychological disorder before onset of fatigue (Group III); and those who had evidence of other medical conditions that could have caused fatigue (Group IV). Patients assigned to Group III were further evaluated to determine the group to which they would have been assigned had psychological illness not been present, the epidemiologic characteristics of the illness and the frequency of symptoms among patients were evaluated, and the prevalence and incidence of CFS were estimated for each of the areas. RESULTS: Of the 648 patients referred to the CFS surveillance system, 565 (87%) agreed to participate. Of these, 130 (23%) were assigned to Group I; 99 (18%), Group II; 235 (42%), Group III; and 101 (18%), Group IV. Of the 130 CFS patients, 125 (96%) were white and 111 (85%) were women. The mean age of CFS patients at the onset of illness was 30 years, and the mean duration of illness at the time of the interview was 6.7 years. Most (96%) CFS patients had completed high school, and 38% had graduated from college. The median annual household income/for CFS patients was $40,000. In the four cities, the age-, sex-, and race-adjusted prevalences of CFS for the 4-year surveillance period ranged from 4.0 to 8.7 per 100,000 population. The age-adjusted 4-year prevalences of CFS among white women ranged from 8.8 to 19.5 per 100,000 population. INTERPRETATION: The results of this surveillance system were similar to those in previously published reports of CFS. Additional studies should be directed toward determining whether the data collected in this surveillance system were subject to selection bias (e.g., education and income levels might have influenced usage of the health-care system, and the populations of these four surveillance sites might not be representative of the U.S. population). ACTIONS TAKEN: In February 1997, CDC began a large-scale, cross-sectional study at one surveillance site (Wichita) to describe more completely the magnitude and epidemiology of unexplained chronic fatigue and CFS.

Immune responses associated with chronic fatigue syndrome: a case-control study.

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies. In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population. However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen.

Characterization of T cell responses to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) using a TNF-beta ELISpot cytokine assay.

We examined the suitability of a TNF-beta cytokine ELISpot assay for assessing various aspects of the T cell response to herpes simplex viruses. The number of T cells responding to HSV-1 or HSV-2 was measured by TNF-beta ELISpot assay. The number of T cells producing TNF-beta in response to HSV-1 was high, ranging from 76 to 222 per 10(5). HSV-1-specific TNF-beta-secreting responder cell frequencies fluctuated over time in individual donors. Comparable fluctuations were not observed in the T cell frequencies to phytohemaglutinin (PHA). Responder cell frequencies to glycoproteins gB and gD of HSV-2 accounted for a large number of the HSV-2-specific T cells as measured using the TNF-beta ELISpot assay. Type-specific and type-common components of the T cell response to HSV-1 and HSV-2 could be estimated with this assay. Type-common responder cells typically accounted for 25-30%. Finally, CD4+ and CD8+ TNF-beta-producing T cells were stimulated by HSV-1 at a CD4:CD8 ratio of 2:1, indicating that both major subsets of T lymphocytes are activated by HSV.

Crack cocaine smoking and oral sores in three inner-city neighborhoods.

Crack cocaine causes blisters, sores, and cuts on the lips and in the mouths of persons who smoke it, and such sores may facilitate the oral transmission of HIV. We recruited young adults aged 18-29 years, who either were current regular crack smokers, or who had never smoked crack, from inner city neighborhoods in New York, Miami, and San Francisco. Participants were interviewed for HIV risk behaviors and history of recent oral sores and were tested for HIV, syphilis, and herpes simplex virus (HSV) antibodies. Among the 2,323 participants recruited, 1,404 (60%) were crack smokers. Crack smokers (10.0%) were more likely than nonsmokers (4.5%) to report having had oral sores in the past 30 days [prevalence odds ratio (POR) 2.4, 95% confidence interval (CI) 1.7-3.4]. Sores were also more prevalent among those who had ever injected drugs (14.3%) than among those who had not (6.7%; POR 2.3, 95% CI 1.7-3.4), and among those with HIV infection (14.3%) than among those without it (8.0%; POR 1.9, 95% CI 1.3-2.8). Among the 429 participants who reported receptive oral sex, those who reported oral sores were more likely than those who did not to have HIV infection, after other HIV risk factors were controlled for (adjusted POR 1.9, 95% CI 1.0-3.6). Our results confirm that crack smokers have a high prevalence of oral sores and provides evidence that these sores, although infrequently, may facilitate oral transmission of HIV.

Seroepidemiology of chronic fatigue syndrome: a case-control study.

We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.