Human herpesvirus 8 infections

Human herpesvirus 8 (HHV-8) or Kaposi’s sarcoma (KS)-associated herpesvirus is a recently identified virus that is associated with KS, multicentric Castleman’s disease, and body cavity-based lymphomas. KS is the most common kind of cancer in AIDS patients and the initial AIDS-defining condition in over 20% of patients. HHV-8 DNA has now been detected in over 95% of KS tissue samples supporting the concept that HHV-8 has a causal role in KS. The discovery has opened new avenues for understanding the epidemiology, pathogenesis, and treatment of KS and related conditions.     

Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman's disease.

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystemic disorder associated with osteosclerotic myeloma and multicentric Castleman's disease (MCD). Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in lymph nodes of about 40% of human immunodeficiency virus (HIV)-negative patients with MCD, and in bone marrow stromal cells of patients with multiple myeloma. Considering these data, we investigated the presence of HHV-8 in 18 patients with POEMS syndrome (9 with MCD), by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in various cells and tissues obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to detect anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had MCD). Detection of HHV-8 DNA was performed using three different N-PCR, targeting nonoverlapping regions in open reading frame (ORF) 25 and ORF26. Seven of 13 (54%) POEMS patients had HHV-8 DNA sequences in their tissues, as assessed by all three N-PCR, and 9 of 18 (50%) had circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the subset of POEMS patients with MCD (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in lymph nodes than in bone marrow samples (P <.02). Sequencing of amplicons showed a homogeneous restricted variability in the ORF26 region, characteristic of the minority subgroup B defined by Zong, and responsible for isoleucine and glycine substitutions at amino acid positions 134 and 167. These findings strongly suggest an association of HHV-8 infection with POEMS syndrome-associated MCD.     

Human herpesvirus 8 infection and Kaposi's sarcoma among human immunodeficiency virus-infected and -uninfected women

Little is known about the epidemiology of human herpesvirus 8 (HHV-8) infections among women. A cross-sectional study was conducted of HHV-8 infection among human immunodeficiency virus (HIV)-infected and high-risk HIV-uninfected women. Serological tests with noninduced (latent) and induced (lytic) HHV-8 antigens were used to detect infection among 2483 participants of a multisite cohort. Reactivity to latent antigen was present in 4.1% and to induced antigens in 12.0% of women. Seven of 8 women who reported Kaposi's sarcoma had HHV-8 antibodies. Among HIV-positive women, HHV-8 infection was associated with use of crack, cocaine, or heroin (76% vs. 65%; P<.001), past syphilis (29% vs. 20%; P<.001), an injection drug-using male sex partner (61% vs. 53%; P=.014), black race (P=.010), and enrollment site (P=.015). In multivariate analysis, HIV infection, older age, past syphilis, black race, and enrollment site were independently associated with HHV-8 infection. In this cohort of North American women, HHV-8 infection was associated with HIV infection, drug use, and risky sexual behavior.     

Diagnosis and epidemiology of human herpesvirus 8 infection

There is consensus that human herpesvirus 8 (HHV-8) is a necessary, albeit not sufficient, causal agent of Kaposi's sarcoma (KS). In the past several years, there have been rapid advances in our understanding of HHV-8 infection. In diagnosis, antibody detection is more sensitive than nucleic acid-based techniques. While initial serologic assays have proven useful in epidemiologic work, their application to individual patient diagnosis is problematic. The major aspects of the epidemiology of HHV-8 infection have been described, but many questions remain. For example, it is not known why there are distinct differences in worldwide distribution, with high prevalence throughout Africa and the Middle East, moderate prevalence in the Mediterranean, and low prevalence in the United States and Northern Europe. There is more than one mode of transmission, and the importance of the type of transmission varies by region. In the United States and Northern Europe, sexual transmission among homosexual men is the most common route of spread, but the specific sexual act(s) responsible are not clear. In high prevalence areas, nonsexual horizontal transmission during childhood is dominant. While saliva is the likely conduit for transmission in highly endemic areas, the precise mechanism for person-to-person spread-and whether this is preventable-is not understood.     

Spread of HIV infection in a rural area of Tanzania.

OBJECTIVE: To assess the spread of HIV into rural areas. METHODS: Since 1994 a demographic surveillance system (with 5-monthly rounds) and open adult cohort study have been established in a rural ward in Tanzania. Two sero-surveys of all resident adults aged 15-44 and 15-46 years were conducted in 1994 1995 and 1996-1997 respectively. Qualitative data were collected on mobility, bars and commercial sex. RESULTS: Attendance of the two rounds of survey was 5820 (78%) and 6413 (80%) in 1994/1995 and 1996/1997 respectively. HIV prevalence increased from 5.8% to 6.6%. HIV incidence was 0.73 and 0.84 per 100 person years among men and women respectively. HIV incidence under the age of 20 years was low among both sexes. Striking differences in HIV prevalence and incidence were observed within the small geographic area studied: HIV prevalence in the trading center was twice that in the area surrounding the trading center (within 2 km) and three to four times that in the rural villages (within 8 km of the trading center). Aggregate level data showed significant differences between the trading center and nearby rural villages in terms of sexual behavior, commercial sex workers, mobility of the population, and alcohol use. CONCLUSION: This study documents the existence of very substantial HIV prevalence and incidence differences within a small geographic rural area. The rapid decrease in HIV prevalence within a small rural area emphasizes the importance of concentrating HIV prevention efforts on high transmission areas, such as trading centers, especially in resource-poor settings. Furthermore, this has considerable implications for monitoring the spread of HIV through sentinel sites, as such sites are typically located in high transmission areas.     

Anaesthesia in rural Tanzania

A survey of the anaesthetic services in rural Tanzania was carried out in an area of 67500 km2 and population of 4 million in order to assess the quality of anaesthesia and the major obstacles to good practice. Lack of draw-over vaporizers, Ayre's T-pieces, and a supply of oxygen were found to be the major obstacles to safe practice in this area of Africa.     

Human herpesvirus type 8 in HIV-infected patients with interstitial pneumonitis

OBJECTIVES: The new human herpesvirus type 8 (HHV-8) has been detected in all types of Kaposi's sarcomas, as well as in body-cavity lymphomas and Castleman's disease. Recently, HHV-8 has also been associated with encephalitis in HIV-positive and HIV-negative patients. Interstitial pneumonitis, combined with detection of HHV-8 in non HIV-infected patients, indicates a pathogenetic role of HHV-8 in unexplained lung diseases. We have studied two HIV-infected patients, with otherwise unexplained interstitial pneumonitis for the presence of HHV-8. METHODS: Lung biopsies of both patients were investigated for HHV-8 sequences. A nested PCR method was used for amplification of HHV-8 DNA fragments, and the nature of the amplification products was confirmed by Southern blot hybridization. In addition, we used an in situ hybridization technique and immunohistochemical staining for detection of HHV-8 infected cells. RESULTS: Amplification of HHV-8 DNA fragments was seen with template DNA from lung biopsies of both cases and the appropriate positive controls, but not with negative controls. In situ hybridization and immunohistochemical staining demonstrated HHV-8 infected lymphoid cells and alveolar macrophages in both patients as well. CONCLUSIONS: HHV-8 was found in HIV-infected patients with otherwise unexplained interstitial pneumonitis, but the pathogenic role of HHV-8 in patients with interstitial pneumonia remains unclear.     

Human herpesvirus 8 cellular immune responses in homosexual men.

Little is known about cellular immunity to human herpesvirus 8 (HHV-8), the virus associated with Kaposi's sarcoma (KS). T cell proliferative responses to purified HHV-8 were measured in homosexual men, a group with elevated HHV-8 seroprevalence and high risk of KS. None of 20 blood donor controls had T cell responses to HHV-8. Among human immunodeficiency virus (HIV)-negative homosexual men, 8 (42%) of 19 HHV-8 seropositive men responded as did 4 (16%) of 25 HHV-8 seronegative men. Among HIV-positive homosexual men, however, none of 21 HHV-8 seropositives had T cell responses to HHV-8, even though most responded to common recall antigens, and 10 had >/=400 CD4 cells/mm3. The results suggest that HHV-8 T cell proliferative responses are common in HIV-negative homosexual men and that HIV infection may be associated with diminished HHV-8 cellular immunity, possibly before there is substantial depletion of CD4 cells. If correct, this could explain why KS occurs relatively early in HIV infection/AIDS.     

Spread of hepatitis C virus infection within families

In 1995, the intrafamilial spread of hepatitis C virus (HCV) was evaluated among 1379 household contacts of 585 HCV antibody-positive HCV RNA-positive subjects (index cases) in Italy. All index cases were patients with histologically proven chronic liver disease. The presence of antibodies to HCV (anti-HCV) was assessed by third-generation enzyme-linked immunosorbent assay (ELISA); the polymerase chain reaction (PCR) was used to test for HCV RNA. The overall anti-HCV prevalence among household contacts of index cases was 7.3% (101/1379); it was 15.6% in spouses and 3.2% in other relatives ( P <0.05; odds ratio (OR), 6.5; 95% confidence interval (CI), 3.5–8.6). Spouses married to index cases for longer than 20 years had a significantly higher anti-HCV prevalence than those married 20 years or less (19.8% vs 8.0%; P <0.05; OR, 2.8; 95% CI, 1.5–5.3). Parenteral risk factors were more likely to be reported in anti-HCV positive than in anti-HCV negative household contacts. After adjustment for confounders by multiple logistic regression analysis, age greater than 45 years (OR, 3.1; 95% CI, 1.6–5.3) and any parenteral exposure (OR, 3.7; 95% CI, 1.7–8.1), were the only independent predictors of the likelihood of anti-HCV positivity among household contacts. Spouses versus other relatives and length of marriage were both no longer associated. These findings suggest that sexual transmission does not seem to play a role in the intrafamilial spread of HCV infection.     

Human herpesvirus 8 virology, epidemiology and related diseases

Human herpesvirus 8 ([HHV-8], Kaposi's sarcoma-associated herpesvirus [KSHV]) is a novel human oncovirus classified as a gamma-herpesvirus. HHV-8 is associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and some cases of multicentric Castleman's disease (MCD). Antibodies against HHV-8 are detected in the sera of almost all KS patients, about 30% of HIV-infected homosexual males in the world and 1.4% of the Japanese population. In HHV-8-associated malignancies such as KS and PEL, HHV-8 latently infects these tumor cells. Unlike other viruses, HHV-8 encodes several human homologues including cytokines (IL-6, MIPs, IRFs) and regulatory proteins (cyclin D, G-protein coupled receptor [GPCR]). These proteins may play significant roles in the pathogenesis of HHV-8-associated diseases. It has been demonstrated in vitro that the functions of retinoblastoma and p53 proteins were inhibited by viral cyclin D and latency-associated nuclear antigen, respectively. Mice transgenic for GPCR have a KS-like region in the skin. These data suggest the full oncogenecity of HHV-8. On the other hand, many cells expressing lytic proteins are found in MCD tissues, suggesting that the pathogenesis of MCD is different from that of HHV-8-associated malignancies.     

农村居民家庭幽门螺杆菌感染的血清流行病学调查

目的:了解幽门螺杆菌(H pylori)感染在农村居民的感染率和探索H pylori感染的传播途径．方法:2004-09对河北省遵化市某村71户家庭263人进行横断面研究,采用面对面问卷调查形式由专人填写调查表,采集静脉血液标本5 mL,用酶联免疫吸附实验(ELISA)方法检测HpUIgG抗体．用免疫印迹方法(Western blot)检测血清中的H pylori抗体．结果:该地区居民的H pylori感染率属于中等水平,男女感染率没有差别．当地居民H pylori感染的危险因素有未成年时住房拥挤、条件差、养猪、现在家庭中几代共同进餐及醋和水果进食过少等．263位受检者中,H pylori总血清感染率为57．41％,抗体平均水平为0．911±0．810μg/L;其中男性感染率为60．50％,抗体平均水平为0．948±0．843μg／L;女性感染率为54．86％,抗体平均水平为0．880±0．784μg／L．H pylori感染有家庭聚集性．父母双方或者一方H pylori感染阳性的其子女H pylori感染率(60％,51．35％)明显高于父母H pylori感染均阴性者(11．11％,P<0．05)．以家庭为单位进行的血清Western blot分析发现各种血缘关系家庭成员,其血清抗体平均相似度较之家庭间成员的平均相似度并没有差别(F=1．22,P>0．05),两两比较结果亦无差别．结论:该地区居民的H pylori感染率属于中等水平,男女感染率没有差别．H pylori感染存在家庭聚集性．     

Human herpesvirus 8-associated multicentric Castleman disease in a patient with advanced HIV infection: A case report

Rational:Multicentric Castleman disease (MCD) is a nonclonal lymphoproliferative disorder that is rarely reported from Southeast Asian countries. Here, we report a case of human herpesvirus 8 (HHV-8)-associated MCD in a patient with advanced human immunodeficiency virus (HIV) infection who presented with prolonged intermittent fever, urticarial rash, hepatosplenomegaly, and generalized lymphadenopathy.Patient concerns:A 34-year-old man with advanced HIV infection who was in good compliance with his antiretroviral treatment regimen presented with intermittent fever, weight loss, marked hepatosplenomegaly, and generalized lymphadenopathy. Recurrent symptoms of high-grade fever, abdominal discomfort, pancytopenia, and high C-reactive protein level occurred for 16 months.Diagnoses:Histopathological findings of left inguinal lymph node revealed diffuse effacement of lymph node architecture with coexpression of HHV-8 latency-associated nuclear antigen 1 from immunohistochemical staining. The HHV-8 viral load was 335,391 copies/mL.Interventions:The patient was treated initially with one dose of intravenous rituximab (375 mg/m²) followed by subcutaneous rituximab (1400 mg) weekly for 5 weeks.Outcomes:The patient''s recurrent systemic symptoms subsided dramatically, and he has now been in remission for almost two years.Lessons:HHV8-associated MCD remains a diagnostic challenge in advanced HIV disease and should be suspected in those with recurrent flares of systemic inflammatory symptoms. Lymph node histopathology is essential for diagnosis and for excluding clonal malignancy. HHV-8 viral load is also useful for diagnosis and for monitoring disease activity.     

Human herpesvirus 6 infection of the gastroduodenal mucosa.

BACKGROUND: Human herpesvirus 6 (HHV-6) infections are usually asymptomatic reactivations in adult liver transplant recipients, but they may also cause fever or graft dysfunction. HHV-6 infection can also present symptoms of gastroenteritis. In this study, we investigated the presence of HHV-6 in the gastroduodenal mucosa of liver transplant recipients and in immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms. METHODS: HHV-6 and cytomegalovirus (CMV) examinations were performed on gastroduodenal biopsy specimens obtained during upper gastrointestinal endoscopic examinations from 90 liver transplant recipients and from 31 immunocompetent patients with upper gastrointestinal symptoms. In the gastroduodenal mucosa, HHV-6 and CMV was demonstrated by immunohistochemistry in frozen sections using monoclonal antibodies against HHV-6- and CMV-specific antigens. RESULTS: HHV-6-positive cells were found in biopsy specimens from 21 (23%) of the liver transplant recipients and 6 (19%) of the immunocompetent patients, CMV-positive cells were found in specimens from 55 (61%) of the transplant recipients and 7 (23%) of the immunocompetent patients, and 12 transplant recipients were found to have both HHV-6 and CMV infection. Fifteen transplant recipients with positive HHV-6 findings in the gastroduodenal mucosa also had HHV-6 antigenemia, whereas 30 patients with HHV-6 antigenemia did not have gastroduodenal involvement. Endoscopic findings in these patients included biliary complications in 10 patients and gastritis in 2 patients. Histopathological findings were nonspecific and included very mild inflammation. A total of 30 (94%) of the transplant recipients with biliary complications also had HHV-6 or CMV detected in the duodenal mucosa. CONCLUSIONS: HHV-6-positive cells and CMV-positive cells were frequently found in the gastroduodenal mucosa of liver transplant recipients and of immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms.     

Human herpesvirus 6 infection of the central nervous system

Human herpesvirus (HHV) 6 infects all children, usually during the first year of life. High fever is the hallmark of primary infection, with febrile seizures the most common complication. After primary infection, HHV-6 remains latent or persistent at multiple sites, with intermittent reactivation. Many disorders of the central nervous system (CNS) have been linked to HHV-6 reactivation, including chronic seizure disorders, encephalitis, and demyelinating disorders including multiple sclerosis. Although multiple studies have pieced together an understanding of the molecular organization, viral characteristics, immunology, and epidemiology of HHV-6, the true role of this virus in diseases of the CNS is still unfolding.     

造血干细胞移植后人疱疹病毒6的感染

造血干细胞移植(HSCT)是治愈血液系统恶性疾病的有效手段,移植后病毒感染是导致移植失败和患者致死的主要原因之一.人疱疹病毒6型(HHV-6)是最近发现的一种新型疱疹病毒,在人群中的感染率非常高,初次感染后潜伏在人体内,当患者免疫功能受到抑制时,病毒再激活并导致一系列威胁生命的并发症.本文综述了HHV-6的生物学特征、对造血干细胞移植产生的可能影响及其治疗.