The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men.

To investigate the relationship between cytomegalovirus (CMV) infection and progression of HIV-1 disease, a group of 234 asymptomatic, HIV-1 antibody-positive homosexual men were examined for CMV isolation and levels of CMV IgM antibodies, CMV IgG antibodies, and CD4+ and CD8+ T-lymphocytes. CMV IgG antibodies were present in 100% and CMV IgM antibodies in 22% of the men. CMV was isolated from the semen of 45% of the men. No relationship was observed between CMV IgM antibodies and CMV in semen or CD4+ levels. CD4+ cell levels were significantly lower in those from whose semen CMV was isolated. In addition, an inverse relationship was observed between the concentration of CMV in semen and CD4+ levels. We postulate that the seminal tract may be a reservoir for systemic CMV infection in HIV-infected homosexual men. Reinfection from this or other sources may result in recurrent stimulation of HIV-1 replication and lead to a further decline in CD4+ cells. Clarification of whether persistent CMV infection is secondary to HIV-1-induced immunodeficiency or, conversely, promotes a more rapid decline in immunocompetency will require follow-up studies.

Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children.

To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed. Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively. These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient). Forty of the 249 days included treatment with vancomycin or amphotericin B. Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy. Two children developed renal dysfunction and eventually succumbed. In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction. Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration. We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized.

Epidemiology of human herpesvirus 6 (HHV-6) infection in pregnant and nonpregnant women.

BACKGROUND: Human herpesvirus 6 (HHV-6) is a ubiquitous virus primarily associated with benign conditions such as febrile syndromes and exanthem subitum (roseola infantum). Sexual, horizontal, and vertical transmission have been suggested. Little information is available regarding HHV-6 infection in women of reproductive age. OBJECTIVE: Describe epidemiology of HHV-6 infection in pregnant and nonpregnant women. STUDY DESIGN: The study sample consisted of 569 women, age 18-45, who attended a university family planning clinic (nonpregnant, n=224) and two obstetrics clinics (pregnant [first trimester], n=345) in San Antonio, TX between October 1995 and May 1998. Blood and a vaginal swab, as well as sociodemographic information, were collected from each participant. Plasma was tested for HHV-6 IgG antibodies using a standard immunofluorescence assay (IFA). Lysed material from vaginal swabs was tested for HHV-6 DNA by polymerase chain reaction (PCR). Products were screened by enzyme-linked immunosorbent assay and positive tests were confirmed by repeat PCR followed by Southern analysis. PCR-positive samples were subtyped using an established method. RESULTS: All subjects were HHV-6 antibody positive. Geometric mean titers of HHV-6 antibodies were significantly higher among nonpregnant versus pregnant women. Moreover, a higher proportion of nonpregnant versus pregnant women had antibody titers >/=160 and >/=320. This association persisted even after adjusting for a number of sociodemographic and clinical factors. Low rates of HHV-6 shedding in the genital tract were observed for both groups (pregnant, 7/297 [2.0%]; nonpregnant, 8/214 [3.7%]). Of 14 samples subtyped, four (29%) were subtype A. CONCLUSION: The present study showed that 100% of the study sample was infected with HHV-6. Higher HHV-6 antibody titers, however, were noted in nonpregnant women. Both groups shed virus at low rates in the genital tract. HHV-6 subtype A was identified more commonly than previously reported. Further longitudinal studies are required to assess the consequences of maternal HHV-6 infection.

The spectrum of mucosa-associated lymphoid tissue lesions in pediatric patients infected with HIV: A clinicopathologic study of six cases.

Mucosa-associated lymphoid tissue (MALT) lesions in nonimmunocompromised individuals include reactive lymphoid proliferations and both low- and high-grade lymphoid neoplasms. These lesions occur at extranodal mucosal sites, such as the gastrointestinal tract, bronchus, salivary gland, and other locations. The spectrum of MALT lesions in children with HIV infection had not been previously described. In this study, six cases that demonstrated the spectrum of MALT lesions in pediatric patients, aged 28 months to 23 years, who had HIV infection were described. Half the patients acquired the infection perinatally, and half acquired it by transfusion. Mucosal sites of involvement included the salivary gland (4 patients), bronchiolar mucosa (2 patients), and oropharyngeal mucosa (1 patient). One patient had lesions in lung and oropharynx sequentially; all others had involvement of solitary sites. The histologic diagnoses included myoepithelial sialadenitis (MESA), MESA with low-grade MALT lymphoma, typical low-grade MALT lymphoma, diffuse large cell lymphoma (DLCL), and atypical pulmonary lymphoid hyperplasia and lymphoid interstitial pneumonitis complex. The two cases of high-grade DLCL were confined to mucosal sites (tonsil and parotid); in one of these patients, a previous biopsy specimen showed a MALT lesion with low-grade features. In two cases, quantitation of the Epstein-Barr virus (EBV) genome by the polymerase chain reaction showed a very high copy number in peripheral blood mononuclear cells but a low copy number in the MALT lesion, which suggested that MALT lesions may not be directly associated with EBV infection. Two patients who had high-grade tumors (DLCL) were successfully treated with chemotherapy and radiation therapy. The remaining patients, all of whom had low-grade MALT lesions, received either corticosteroids or alpha-interferon or no specific therapy; in all patients, the lesions followed an indolent clinical course. Clinicians and pathologists should be alert to the possibility that MALT lesions, including MALT lymphomas, may be present in children who have AIDS.

Prevalence of Cryptosporidium parvum infection in children along the Texas-Mexico border and associated risk factors.

We examined the epidemiology of Cryptosporidium parvum in children aged 6 months to 13 years living in 1) colonias along the border (n = 105), 2) a clinic in an urban border community (n = 65), and 3) clinics in a large urban nonborder area (n = 109). Serum IgG and IgA anticryptosporidial antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Overall, 70.2% (196/279) of subjects had detectable C. parvum antibodies. Prevalence rates were higher (93/105 [89%]) in the colonias and urban border community (53/65 [82%]) compared to the urban nonborder community (50/109 [46%]). Within colonias, independent risk factors for C. parvum infection included consumption of municipal water instead of bottled water, older age, and lower household income. Children living along the Texas-Mexico border have a higher rate of infection with C. parvum compared to children living in a large nonborder urban area. Within colonias, C. parvum infection was associated with source of water supply, age, and socioeconomic status.

Benign and malignant smooth muscle tumors containing Epstein-Barr virus in children with AIDS.

Smooth muscle tumors (leiomyosarcomas) are the second most prevalent malignancy of children with the acquired immunodeficiency syndrome (AIDS). We have investigated the tumors, plasma, and peripheral white blood cells of eight children with AIDS with smooth muscle tumors for evidence of tumor association with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Very low levels of HIV were found in the tumors of the AIDS patients, probably resulting from blood-borne carriage of virus. These smooth muscle tumors had very high quantities of EBV in all the tumor cells by in situ hybridization, with an average of 4.5 EBV genomes per cell by quantitative polymerase chain reaction amplification. Increased amounts of EBV were found in the peripheral blood cells of two AIDS patients before the time of tumor diagnosis. EBV clonality studies demonstrated different monoclonal EBV infection of two separate colonic tumors from one patient, and dual or mixed monoclonal EBV infection in another patient. The muscle cells of leiomyomas and leiomyosarcomas of patients with AIDS demonstrated prominent staining with antibodies to the EBV receptor. The uniform distribution and striking amount of EBV in the tumor cells demonstrates that EBV is capable of infecting smooth muscle cells and that these cells support EBV replication. Clonal EBV proliferation suggests that EBV infection occurs at an early stage of tumor development. These findings indicate that EBV has a causal role in the oncogenesis of leiomyosarcomas of patients with AIDS.

Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes.

Human herpesvirus-6 (HHV-6) and -7 (HHV-7) infections typically are silent or manifested as mild febrile illnesses including classic roseola. In addition, case reports and epidemiologic data support the rare occurrence of HHV-6 encephalitis in immunocompromised as well as immunocompetent subjects. Although many other diseases have been putatively associated with HHV-6 or HHV-7, these associations are not well documented due to small numbers, use of tests incapable of distinguishing latent from replicating virus, potential virus cross-reactivity, or contradictory results. Further careful studies are needed to confirm these disease associations. Laboratory tests for diagnosing active HHV-6 and HHV-7 infections include virus culture, antigen detection, and polymerase chain reaction of cell-free biologic fluid. Although HHV-6 and HHV-7 are inhibited by several antiviral drugs in the laboratory, including ganciclovir and foscarnet, no clinical trials have assessed their benefit. Nevertheless, treatment may be considered for patients with serious HHV-6- or HHV-7-associated disease confirmed with accurate virologic tests.

Antiretroviral prescribing patterns in the Texas prison system.

Although the prevalence of human immunodeficiency virus (HIV) infection among prison inmates is reported to be high, little is known about anti-HIV treatment patterns in correctional institutions. The present study assessed antiretroviral prescribing patterns for 2360 Texas Department of Criminal Justice (TDCJ) inmates infected with HIV. In 1998, 66.8% of all TDCJ inmates infected with HIV who had CD4 lymphocyte counts < 500 cells/mm(3) were treated with highly active antiretroviral therapy (HAART). However, no substantial differences in the use of HAART were exhibited according to the sociodemographic factors under study. While the majority of inmates receiving HAART in 1998 were prescribed a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 protease inhibitor, 11.2% were prescribed a combination of 2 NRTIs and 1 non-NRTI. In view of the elevated rate of HIV infection in correctional settings, it will be important to continue to document the pharmacotherapy patterns among prison inmates, both during and following incarceration.

The epidemiology of viral hepatitis in children in South Texas: increased prevalence of hepatitis A along the Texas-Mexico border.

An initial retrospective study of 194 children demonstrated a high prevalence of hepatitis A but not hepatitis B or C infection among children living along the Texas-Mexico border. A larger prospective study of hepatitis A was conducted with 285 children (aged 6 months to 13 years) living in 3 sociodemographically dissimilar areas of South Texas. Children living in colonías along the border had a significantly higher prevalence of hepatitis A virus infection (37%) than children living in urban border communities (17%) or in a large metropolitan area (San Antonio [6%]). Independent risk factors for hepatitis A infection included increased age, colonía residence, and history of residence in a developing country. Use of bottled water (vs. municipal or spring/well water) and years of maternal secondary education were protective. Improved sanitation or routine hepatitis A vaccination in early childhood may reduce the prevalence of hepatitis A in these areas.

Human herpesvirus 6 infection of the female genital tract.

Four of the seven human herpesviruses are recognized to replicate in the female genital tract and may be transmissible to sexual partners and newborn infants. Several of these viruses have also been implicated in the etiology of various human cancers, including tumors of epithelial cell origin. Human herpesvirus 6 (HHV-6) is a newly identified herpesvirus that causes exanthem subitum. The pathogenicity of HHV-6 within the genital tract is largely unexplored. Acellular vaginal secretions from 29 women attending a sexually transmitted diseases clinic were examined for the presence of HHV-6 DNA sequences by polymerase chain reaction. Three samples (10%) were consistently positive for HHV-6 DNA. Since HHV-6 DNA is shed in the genital tract of some women, it is possible that infectious virus is transmissible through sexual contact and to newborn infants by perinatal spread.

Evaluation of human herpesvirus type 8 infection in childhood langerhans cell histiocytosis.

The etiology of Langerhans cell histiocytosis (LCH) is unknown. Viral causes, including human herpesvirus type 6 (HHV6), have been suggested but remain unproved. The recently discovered human herpesvirus type 8 (HHV8), the cause of Kaposi's sarcoma, infects dendritic cells in the bone marrow associated with multiple myeloma. Evidence for an association of HHV8 infection with LCH in children was studied by two approaches: indirectly by HHV8-specific serologic assays and directly by detection of HHV8 sequences using polymerase chain reaction in affected bone marrow samples. Using three different assays specific for HHV8 antibodies, 3 of 10 (30%) children with LCH had detectable HHV8 antibodies, which was not different from the prevalence of 5 of 30 (17%) in healthy controls of similar age (P = 0.65). Of bone marrow samples from three additional children with LCH, all had amplifiable DNA but were negative for HHV8 sequences. These studies of a small number of patients do not demonstrate an increased prevalence of HHV8 infection in children with LCH, and they do not suggest a causal role for HHV8 in the etiology of LCH.

A longitudinal study of cytomegalovirus infection in human immunodeficiency virus type 1-seropositive homosexual men: molecular epidemiology and association with disease progression.

Cytomegalovirus (CMV) isolates from 234 asymptomatic human immunodeficiency type 1 (HIV-1)-positive men were analyzed for molecular relatedness using junctional hybridization. Of isolates shed simultaneously at two or more body sites, 36% from 22 men were different. Of 180 isolates collected from 67 men over 15 months, different strains were isolated serially from 27 men (40%), most from semen. After follow-up of 58 months (mean), the relative hazard of HIV infection progressing to AIDS was 1.8 (95% confidence interval [CI], 0.9-3.7) for men shedding the same strain of CMV and 3.0 (95% CI, 1.4-6.1) for men shedding different strains compared with men not shedding CMV in semen. The prevalence of CMV-specific IgM was higher in men shedding different versus same CMV strains (32% vs. 18%; P = .244). Thus, presence of multiple CMV strains in HIV-1-positive homosexual men is associated with progression to AIDS, possibly via activation of HIV-1-infected CD4 cells.

Relapsing pneumococcal bacteremia in immunocompromised patients.

Relapse of Streptococcus pneumoniae bacteremia after appropriate therapy is thought to be rare, even in immunocompromised patients. We describe three immunodeficient patients who experienced repeated episodes of pneumococcal bacteremia within 8 weeks after receiving appropriate therapy. Serotyping and DNA fingerprinting of respective isolates strongly suggested that each patient's bacteremic relapse was caused by the same pneumococcal strain. Relapsing and recurrent infections with an identical pneumococcal strain, especially in immunodeficient individuals, may be more common than is generally appreciated.

Persistent cytomegalovirus infection of semen increases risk of AIDS.

To evaluate if persistent cytomegalovirus (CMV) infection of semen in human immunodeficiency virus type 1 (HIV-1) antibody-positive men increases AIDS risk, serial cultures for CMV every 3-6 months were attempted four or more times from 164 men followed 3 years. CMV was never isolated from 58 men, in 1 or 2 samples from 54 (intermittently positive), and in > or = 3 samples from 52 (persistently positive). The Cox model was used to estimate relative hazards while controlling for CD4 cell number. The relative hazard was 2.9 for those intermittently and 4.0 for those persistently positive (P < .001). No Kaposi's sarcoma occurred in culture-negative men, 3 cases (5.6%) in intermittently positive men, and 4 cases (7.7%) in persistently positive men (P < .04). Persistent CMV in semen increases the hazard of AIDS in HIV-1 antibody-positive men, possibly by activating CD4 cells to produce HIV-1. Thus, control of CMV in HIV-1-infected persons may slow progression to AIDS.

Elastin covalent structure as determined by solid phase amino acid sequencing.

The amino acid sequences of 16 large tryptic fragments of aortic tropoelastin have been determined establishing the presence of several repeating structures: GVP, GGVP, PGVGV, PGVGVA, and AGVPGFGVG. The methodologies for achieving these results by solid phase sequencing are reviewed and also the possible biologic significance of the unusual primary structures of elastin are discussed.

Frequency of unrecognized Bordetella pertussis infections in adults.

To investigate the frequency of unrecognized Bordetella pertussis infections in adults, we performed IgA and IgG ELISA antibody studies with four B. pertussis antigens--i.e., lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in 51 health care workers from whom six consecutive yearly serum samples (from 1984 to 1989) were available. Overall, 90% of the subjects had a significant increase in antibody (IgA or IgG) to one or more antigens between 2 consecutive years during the 5-year study period; 55% of subjects had evidence of two infections, 17% had three infections, and 4% had four infections. Infections occurred in all study years, with the following rates: 1984-1985, 32%; 1985-1986, 24%; 1986-1987, 40%; 1987-1988, 29%; and 1988-1989, 43% (P = .12). Some antibody rises may have been due to responses to cross-reacting antigens (Bordetella parapertussis, nontypable Haemophilus influenzae), but overall these data suggest that B. pertussis infections in adults are common, endemic, and usually unrecognized.

Molecular and virologic characteristics of lymphoid malignancies in children with AIDS.

PURPOSE: To characterize AIDS-associated lymphoid malignancies in children. PATIENTS AND METHODS: We studied lymphomas and B-cell leukemias from 25 children with AIDS for immunoglobulin heavy chain gene clonality, c-myc oncogene abnormalities, and presence of HIV and Epstein-Barr virus. RESULTS: Monoclonal immunoglobulin gene rearrangements were identified in 22 of 23 cases tested, the single exception being one of mucosa-associated lymphoid tissue. Immunoglobulin gene/c-myc translocations were found in 3 of 4 cases of B (surface immunoglobulin-positive)-acute lymphoblastic leukemia, 8 of 11 small noncleaved cell lymphomas, and 1 of 5 large cell lymphomas. Mutations of c-myc were found in 2 of 13 small noncleaved cell lymphomas, 1 of 2 Epstein-Barr virus-positive mucosa-associated lymphoid tissue neoplasms, and 1 of 4 Epstein-Barr virus-negative B-acute lymphoblastic leukemia. Six small noncleaved cell lymphomas, both mucosa-associated lymphoid tissue neoplasms and one of large cell lymphoma had high levels of Epstein-Barr virus in tumor tissue. Hodgkin's disease tissue and B-acute lymphoblastic leukemia tumors were negative for EBV. Proviral HIV-1 was not detected in any tumor. CONCLUSIONS: AIDS-associated lymphoid malignancies in children appear to have a different distribution of histologic subtypes than adult HIV-infected individuals, fewer large cell lymphomas occur in children. The small noncleaved cell lymphomas exhibit a lower frequency as well as different locations of c-myc mutations than AIDS-associated small noncleaved cell lymphomas in adults.

Antibodies to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma.

Kaposi's sarcoma-associated herpesvirus (KSHV) serologic assays were used to detect specific antibodies to KSHV lytic and latent antigens in 27 patients with multiple myeloma, 27 control patients with other cancers, and 50 random blood donors. Antibodies to KSHV recombinant minor capsid antigen orf65 were found in 81% of patients with multiple myeloma, 22% of control patients with other cancers, and 6% of the blood donors. Antibodies to KSHV latent nuclear antigens were found in 52% of patients with multiple myeloma, 26% of control patients with other cancers, and 2% of the blood donors. All of the 11 patients with progressive multiple myeloma were KSHV-seropositive. Antibodies to Epstein-Barr virus nuclear antigen 1 were present in 89% of patients with multiple myeloma, 93% of control patients with other cancers, and 88% of the blood donors. These data support the possible association of KSHV infection with multiple myeloma, particularly with progressive disease.

Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS.

BACKGROUND: Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein-Barr virus (EBV). METHODS: Tissue specimens of five leiomyosarcomas and two leiomyomas from six children with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed. RESULTS: In situ hybridization showed EBV genomes in all muscle cells of the five leiomyosarcomas and the two leiomyomas from the six HIV-infected children. Quantitative PCR demonstrated strikingly high levels of EBV in tumor tissue, with as many as 4.3 genome copies per cell. Two colonic leiomyosarcomas obtained from different sites at different times from one patient contained different episomal EBV clones, signifying the presence of distinct monoclonal EBV-related tumors. We found biclonal EBV infection in the leiomyosarcoma of another patient. No EBV was detected in normal muscle or tumor specimens from HIV-negative patients. Immunostaining for the EBV receptor was strongly positive in six of the seven leiomyomas and leiomyosarcomas from the patients with AIDS. CONCLUSIONS: EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in children with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative children.