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Eric A Engels

Publications and source records attributed to Eric A Engels.

51 records · Page 3Linked to original sources
PubMed2003

Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDS-associated Kaposi's sarcoma.

OBJECTIVE: To identify immunologic and virologic predictors of AIDS-associated Kaposi's sarcoma (KS). DESIGN: Nested case-control analysis of KS risk in a cohort of 132 HIV-infected homosexual men in New York and Washington, DC, USA. METHODS: For each KS case, we selected two HIV-infected controls, matched for CD4 cell count and Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8; KSHV) serostatus (enzyme immunoassay for antibody to KSHV protein K8.1). Cell-associated KSHV and Epstein-Barr virus (EBV) viral loads were measured with quantitative real-time PCR assays on samples collected 1 year (median) before KS diagnosis. RESULTS: Thirty-one men developed AIDS-associated KS (incidence 3.1 per 100 person years). Among HIV-infected men, KS incidence was higher among those with K8.1 seropositivity (5.0 versus 1.4 per 100 person years; P = 0.004), low CD4 cell count [hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.24-1.79 per 100 x 10(6) cells/l decline), or high HIV RNA level (HR, 3.96; 95% CI, 2.19-7.16 per log(10)). In the case-control analysis, nine of 70 evaluated subjects had KSHV viremia, generally low level (median viral load 180 copies per 1 x 10(6) cells). KSHV viremia was associated with increased KS risk (unadjusted odds ratio, 9.1; 95% CI, 1.7-48; odds ratio, 11.7; 95% CI, 1.8-76 after adjustment for K8.1 serostatus, CD4 cell count, and HIV RNA). Among K8.1-seropositive subjects, KS incidence was tenfold higher in those with KSHV viremia (30.3 per 100 person years versus 3.4 per 100 person years in those without viremia). Also, EBV viral loads were higher in cases than in controls (P = 0.07). CONCLUSIONS: Among individuals with HIV-KSHV coinfection, KSHV viremia identifies a subgroup with extremely high risk for developing KS.

Adult↗
PubMed2003

Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies.

The cause of thymoma is unknown. No population-based study has described demographic patterns of thymoma incidence. Previous reports have linked thymoma with diverse subsequent malignancies, but these associations are uncertain. We used Surveillance, Epidemiology and End Results (SEER) data to study the incidence of malignant thymoma by sex, age and race in the United States (1973-1998). Incidence was modeled with joinpoint regression (for age) and Poisson regression. We also used SEER data to compare malignancies following thymoma diagnosis with those expected from general population rates, calculating the standardized incidence ratio (SIR, observed/expected cases) to measure risk. The overall incidence of malignant thymoma was 0.15 per 100000 person-years (849 cases). Thymoma incidence increased into the 8th decade of age and then decreased. Incidence was higher in males than females (p=0.007) and was highest among Asians/Pacific Islanders (0.49 per 100000 person-years). Following thymoma, there were 66 malignancies (SIR 1.5, 95%CI 1.2-1.9). The most notable excess risk for subsequent malignancy was for non-Hodgkin's lymphoma (B immunophenotype) where the SIR was 4.7 (95%CI 1.9-9.6, 7 cases). There were also excess digestive system cancers (SIR 1.8, 95%CI 1.1-2.9) and soft tissue sarcomas (SIR 11.1, 1.3-40.1). No other cancers were increased after thymoma. In conclusion, malignant thymoma is extremely rare. The peak in late adulthood deserves further study. Variation in incidence by race suggests a role for genetic factors. Our study did not demonstrate broadly increased risk for malignancies following thymoma.

Adult↗
PubMed2003

Lack of serological evidence for an association between simian virus 40 and lymphoma.

Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain.

Antibodies, Viral↗
PubMed2003

Immune deficiency and risk for malignancy among persons with AIDS.

BACKGROUND: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset. METHODS: We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm3, 50-99 cells/mm3, 100-199 cells/mm3, and > or =200 cells/mm3) was modeled using Poisson regression. RESULTS: The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm3, RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR =1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm3) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p =.74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts. CONCLUSION: SKS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.

Adolescent↗
PubMed2003

Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40.

BACKGROUND: Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts. METHODS: Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0-4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided. RESULTS: After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955-1961) or children (i.e., born 1946-1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964-1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0-4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95%CI = 1.36 to 4.92; P =.004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40. CONCLUSION: Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence.

Child, Preschool↗
PubMed2003

Seroprevalence of human herpesvirus 8 among injection drug users in San Francisco.

The association between injection drug use and human herpesvirus 8 (HHV-8) was examined to investigate bloodborne transmission of the virus. In all, 1905 injection drug users (IDUs) enrolled in a cross-sectional study were tested for K8.1 antibodies to HHV-8 lytic antigen. Logistic regression was used to adjust for demographic and sexual behavior variables. HHV-8 seroprevalence was 10% among women, 10% among heterosexual men, and 23% among men who have sex with men. In adjusted analyses, HHV-8 seroprevalence increased with longer duration of injection drug use for each of these groups (P = .01, P = .03, and P = .049 for trend, respectively). HHV-8 infection is relatively common among IDUs in San Francisco, and longer duration of injection drug use is associated with an increase in the risk of HHV-8 infection that is not explained by sexual behavior or demographic differences. These results are consistent with the occurrence of bloodborne transmission of HHV-8 among IDUs.

Adult↗
PubMed2003

Immunoblastic lymphoma in persons with AIDS-associated Kaposi's sarcoma: a role for Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus, the viral agent of Kaposi's sarcoma, is associated with two lymphoproliferative disorders: primary effusion lymphoma and multicentric Castleman's disease. To identify other lymphoproliferative conditions linked with Kaposi's sarcoma-associated herpesvirus, we studied non-Hodgkin's lymphomas arising in individuals with AIDS-associated Kaposi's sarcoma. Formalin-fixed tissues from 24 such lymphomas were examined. As expected, two primary effusion lymphomas were Kaposi's sarcoma-associated herpesvirus-positive, with immunohistochemistry demonstrating the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen in the nuclei of all neoplastic cells. Additionally, three of seven evaluable cases of the immunoblastic variant of diffuse large B-cell lymphoma (immunoblastic lymphoma) showed similar latency-associated nuclear antigen staining. These Kaposi's sarcoma-associated herpesvirus-positive immunoblastic lymphomas resembled primary effusion lymphoma histologically but were not known to involve body cavities (sites included lymph nodes, soft tissues of the neck, and spleen). Notably, 5-20% of the neoplastic cells in the Kaposi's sarcoma-associated herpesvirus-positive immunoblastic lymphomas also showed cytoplasmic staining for viral interleukin-6, a biologically active cytokine homologue found in primary effusion lymphoma. We conclude that Kaposi's sarcoma-associated herpesvirus is present in some immunoblastic lymphomas in persons with AIDS-associated Kaposi's sarcoma.

AIDS-Related Opportunistic Infections↗
PubMed2002

Prevalence of hepatitis C virus infection and risk for hepatocellular carcinoma and non-Hodgkin lymphoma in AIDS.

Hepatitis C virus (HCV) infection is highly prevalent in some subpopulations with AIDS. HCV is linked to hepatocellular carcinoma (HCC) and possibly non-Hodgkin lymphoma (NHL), but the impact of AIDS on these associations is uncertain. We used U.S. registry data to study HCC and NHL risk in 304,411 adults with AIDS, comparing cohort subgroups with high prevalence (hemophiliacs and injection drug users) or low prevalence (homosexual men, heterosexuals, and others) of HCV infection. The ratio of observed to expected cancer cases (standardized incidence ratio [SIR]) measured risk relative to the general population. Sixty-one HCC cases were observed (SIR, 7.5; 95% confidence interval, 5.7-9.6). Risk for HCC was higher in subgroups with high prevalence of HCV infection than in subgroups with low prevalence of HCV infection (SIR: 11.4 versus 5.5, respectively; p =.004). Subjects developed the following NHL grades: low, 35 cases; intermediate, 1035 cases; high, 784 cases; and unspecified, 1395 cases. For each NHL grade, SIRs were highest in subgroups with low prevalence of HCV infection. These data suggest an effect of HCV infection on HCC risk among adults with AIDS. On the other hand, NHL risk was not higher for groups in whom HCV infection was prevalent.

AIDS-Related Opportunistic Infections↗
PubMed2002

Antibody reactivity to latent and lytic antigens to human herpesvirus-8 in longitudinally followed homosexual men.

Tests for human herpesvirus-8 (HHV-8) often disagree on which individuals are infected. To evaluate HHV-8 antibody changes over many years, 245 homosexual men enrolled in a prospective study between 1982 and 1999 were studied. Samples collected annually were evaluated by immunofluorescence to HHV-8 latent nuclear antigen and by an ELISA for antibody against the HHV-8 lytic antigen K8.1. When positive, samples from most subjects were persistently reactive in both assays. Titers to both lytic and latent antibodies increased for many years, usually in parallel, and were higher in human immunodeficiency virus-infected men. The increasing titers and expanding epitope recognition suggest ongoing, low-grade replication of HHV-8. Use of multiple assays is important in determining prevalence in asymptomatic populations. Because persons with more advanced infections have higher antibody titers, they are easier to detect, which may skew our understanding of the epidemiology of HHV-8.

Antibodies, Viral↗
PubMed2002

Absence of simian virus 40 in human brain tumors from northern India.

Simian virus 40 (SV40), a monkey polyomavirus, was a contaminant of early poliovirus vaccines administered to millions of individuals in the 1950s and early 1960s. SV40 causes brain tumors in laboratory animals, and SV40 DNA sequences have been variably identified in human choroid plexus tumors and ependymomas. We studied the possible association between SV40 and human brain tumors in northern India, where humans have frequent contact with SV40-infected rhesus macaques. DNA from pathologic specimens from 33 ependymomas, 14 choroid plexus tumors and 18 control brain tissues (contused brain, brain metastases) was extracted and analyzed under masked conditions. We used real-time PCR to detect and quantify SV40 (T antigen) and human (GAPDH) DNA sequences. The SV40 PCR assay detected as few as 10 copies of SV40 DNA and had a linear range from 1 x 10(2) to 1 x 10(6) copies. SV40 DNA was detected in 1 specimen (an ependymoma). However, few SV40 DNA copies were detected in this sample (<10 copies, equivalent to <1 copy/350 cells, based on simultaneous GAPDH quantification), and SV40 was not detected when this sample was retested. Our findings do not support a role for SV40 in choroid plexus tumors or ependymomas from northern India.

Adolescent↗
PubMed2002

Pleural and peritoneal lymphoma among people with AIDS in the United States.

OBJECTIVE: To describe the occurrence and characteristics of pleural and peritoneal lymphoma in a large cohort of persons with AIDS in 11 regions in the United States. METHODS: We used AIDS and cancer registries to identify cases of non-Hodgkin lymphoma (NHL) among 304,439 adults with AIDS. NHLs were categorized by site codes into pleural/peritoneal lymphoma and other NHLs. Data on age, sex, HIV exposure category, histology, history of Kaposi sarcoma (KS), CD4 counts, and survival were analyzed. RESULTS: Fourteen lymphomas were identified (four within the pleura, 10 in the peritoneum) representing 0.13% (95% confidence interval [CI], 0.05-0.20) of 10,510 cases of NHL. Those with pleural/peritoneal lymphoma were similar to those with other NHLs in age (median, 43 years), race (79% white, 7% black, 14% Hispanic), and HIV transmission category (86% homosexual men), but they tended to have a higher prevalence of prior KS (29% vs. 12%; p =.06). More cases of pleural/peritoneal lymphoma had immunoblastic histology than did other NHLs (43% vs. 22%; p =.06). CD4 counts for pleural/peritoneal lymphomas were also higher than for other NHLs (median 203 vs. 65 cells/mm3; p =.05), but post-NHL survival was similar (median 7.1 vs. 5.1 months, respectively; p =.32). CONCLUSIONS: Pleural and peritoneal lymphomas are a rare subtype of AIDS-associated NHL, occurring with less severe immune deficiency than for other NHLs. The increased frequency among persons with prior KS suggests a common etiology, presumably infection with KS-associated herpesvirus, as found in primary effusion lymphoma.

Adult↗
PubMed2002

Merkel cell carcinoma and HIV infection.

Merkel cell carcinoma (MCC) is a rare skin cancer that occurs more frequently after organ transplantation or B-cell malignancy, conditions of suppressed or disordered immunity. To assess further whether immune suppression increases MCC risk, we studied its occurrence in a cohort of 309365 individuals with acquired immunodeficiency syndrome (AIDS) by using linked AIDS and cancer registries. We identified six cases of MCC, corresponding to a relative risk of 13.4 (95% CI 4.9-29.1) compared with the general population. These results suggest that immune suppression induced by the human immunodeficiency virus increases MCC risk.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Kaposi's sarcoma-associated herpesvirus infection in elderly Jews and non-Jews from New York City.

BACKGROUND: Worldwide, Kaposi's sarcoma (KS) occurs in immunocompetent elderly adults, especially men. Elderly Jews have relatively high KS risk, but it is unclear whether this indicates heightened prevalence of KS-associated herpesvirus (KSHV), the KS agent. We studied Jewish and non-Jewish patients at a New York City geriatrics clinic. METHODS: We measured plasma antibodies against K8.1 (a KSHV glycoprotein) by enzyme immunoassay and against viral latency antigens by immunofluorescence assay. Individuals positive by either were considered KSHV-seropositive. Titres were performed for positive subjects. We used polymerase chain reaction to quantify circulating KSHV DNA. RESULTS: Of 467 subjects (median age 80 years), 40 were KSHV-seropositive (8.6%). Seroprevalence was 8.8% among Jews (18 of 204), similar to other religious groups, and did not differ by sex or region of birth. However, K8.1 antibody titres were higher in men than women (geometric mean titre 177 versus 35, P = 0.03) and increased with age (P = 0.02). The K8.1 titres were higher in three people from Central/Eastern Europe (1,280, 1,280, 320), all of whom were Jewish, than in others (geometric mean titre 39, P = 0.006). The single person with detectable circulating KSHV (457 copies/million cells) had the highest titre (5,120). CONCLUSIONS: The KSHV seroprevalence was not elevated among elderly Jews, despite their known high risk for KS. However, among KSHV-seropositive individuals, K8.1 titres were highest in subgroups at greatest risk for KS (men, older individuals, people from Central/Eastern Europe) and may identify individuals with poor immune control of KSHV replication during asymptomatic infection.

Age Distribution↗