Estimation of the worldwide seroprevalence of cytomegalovirus : a systematic review and meta-analysis

Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality

CMV retinitis in China and SE Asia: the way forward

AIDS-related CMV retinitis is a common clinical problem in patients with advanced HIV/AIDS in China and Southeast Asia. The disease is causing blindness, and current clinical management, commonly characterized by delayed diagnosis and inadequate treatment, results in poor clinical outcomes: 21% - 36% of eyes with CMV retinitis are already blind at the time the diagnosis is first established by an ophthalmologist. CMV retinitis also identifies a group of patients at extraordinary risk of mortality, and the direct or indirect contribution of extra-ocular CMV disease to AIDS-related morbidity and mortality is currently unmeasured and clinically often overlooked. The obvious way to improve clinical management of CMV retinitis is to screen all patients with CD4 counts < 100 cells/μL with indirect ophthalmoscopy at the time they first present for care, and to provide systemic treatment with oral valganciclovir when active CMV retinitis is detected. Treatment of opportunistic infections is an integral part of HIV management, and, with appropriate training and support, CMV retinitis screening and treatment can be managed by the HIV clinicians, like all other opportunistic infections. Access to ophthalmologist has been problematic for HIV patients in China, and although non-ophthalmologists can perform screening, sophisticated ophthalmological skills are required for the management of retinal detachment and immune recovery uveitis, the major complications of CMV retinitis. CMV retinitis has been clinically ignored, in part, because of the perceived complexity and expense of treatment, and this obstacle can be removed by making valganciclovir affordable and widely available. Valganciclovir is an essential drug for developing successful programs for management of CMV retinitis in China and throughout SE Asia

Cotrimoxazole reduces systemic inflammation in HIV infection by altering the gut microbiome and immune activation

Wellcome TrustCanadian Institutes of Health ResearchMedical Research CouncilDepartment for International Development under MRC/DFID Concordat agreement and EDCTP2 programme supported by the European UnionMRC Clinical Trials Unit at UC

Cytomegalovirus Infection of the Colon Presenting as a Mass-Like Lesion

Cytomegalovirus (CMV) is responsible for the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS). The colon is a common site for these infections in patients positive for human immunodeficiency virus. CMV rarely presents as an intraluminal inflammatory mass in the colon. Here we report the case of a CMV infection presenting as a mass-like lesion in an AIDS patient. The clinical diagnosis of CMV infection is largely based on the characteristic endoscopic appearance. Endoscopic procedures are encouraged early in the course of CMV infection in immunocompromised patients. CMV pseudotumors along with malignancy should be part of the endoscopic evaluation in patients with AIDS

Cytomegalovirus Viremia as a Risk Factor for Mortality Prior to Antiretroviral Therapy among HIV-Infected Gold Miners in South Africa

BACKGROUND: Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV. METHODS: Using a cohort of mineworkers with stored plasma samples, we investigated the association between CMV DNA concentration and mortality prior to antiretroviral therapy availability. RESULTS: Among 1341 individuals (median CD4 count 345 cells/µl, 70% WHO stage 1 or 2, median follow-up 0.9 years), 70 (5.2%) had CMV viremia at baseline; 71 deaths occurred. In univariable analysis CMV viremia at baseline was associated with a three-fold increase in mortality (hazard ratio [HR] 3.37; 95% confidence intervals [CI] 1.60, 7.10). After adjustment for CD4 count, WHO stage and HIV viral load (N = 429 with complete data), the association was attenuated (HR 2.27; 95%CI 0.88, 5.83). Mortality increased with higher CMV viremia (≥1,000 copies/ml vs. no viremia, adjusted HR 3.65, 95%CI: 1.29, 10.41). Results were similar using time-updated CMV viremia. CONCLUSIONS: High copy number, subclinical CMV viremia was an independent risk factor for mortality among male HIV-infected adults in South Africa with relatively early HIV disease. Studies to determine whether anti-CMV therapy to mitigate high copy number viremia would increase lifespan are warranted

CMV quantitative PCR in the diagnosis of CMV disease in patients with HIV-infection – a retrospective autopsy based study

Background Patients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease. Earlier studies of patients with HIV infection have demonstrated that the diagnosis is often first made post-mortem. In recent years new molecular biological tests have become available for diagnosis of CMV disease. Although clinical evaluation of tests for diagnosis of CMV disease in HIV-infected individuals is suboptimal without autopsy, no results from such studies have been published. The aim of this study was to explore the diagnostic utility of CMV quantitative polymerase chain reaction (PCR) in plasma from HIV and CMV seropositive patients who died during the period 1991–2002 and in whom autopsy was performed. Methods Autopsy was performed in all cases, as part of routine evaluation of HIV-infected cases followed at Ullevaal University Hospital. Of 125 patients included, 53 had CMV disease, 37 of whom were first diagnosed at autopsy. CMV disease was diagnosed either by ophthalmoscopic findings typical of CMV retinitis, biopsy or autopsy. One or two plasma samples taken prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease were analysed by CMV quantitative PCR. Sensitivity, specificity, positive and negative predictive values were calculated for different CMV viral load cut-offs and according to detection of viraemia in one versus two samples. Results Twenty-seven of 53 patients with CMV disease (51%) and 10 of 72 patients without CMV disease (14%) had detectable viraemia in at least one sample. Sensitivity and negative predictive value (NPV) of the test, maximised with a cut-off at the test's limit of detection of CMV viraemia (400 copies/mL), were 47% and 70%, respectively. With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%. With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection. Conclusion Our results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk

Contrasting Roles for TLR Ligands in HIV-1 Pathogenesis

The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention