Cytomegalovirus DNA Polymerase Chain Reaction Research Articles

Dual bombard by Cytomegalovirus and Mycobacterium tuberculosis in a renal transplantee

Abstract In the first year following an organ transplant, more than 80% of patients encounter a minimum of one occurrence of infection. Here, we report a case of coinfection of the Cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB) in a kidney transplantee. Computed tomography chest (CT chest) showed bilateral ground-glass opacities. By Cytomegalovirus DNA polymerase chain reaction, 9360 copies were detected in plasma. Cartridge-based nucleic acid amplification test from bronchial washings tested positive for MTB with very low-level resistance to rifampicin. He was started on category-I antitubercular therapy without rifampicin and intravenous valganciclovir. The clinical status of the patient improved after 1 month of treatment.

A Prospective Study of Plasma and Bronchoalveolar Lavage Fluid CMV DNA Load Quantification for the Diagnosis and Outcome of CMV Pneumonitis in Immunocompromised Hosts.

Molecular testing has been utilized for cytomegalovirus (CMV) pneumonitis (CMVP) diagnosis, although its validity and optimal cut-off values remain limited. A prospective study of CMVP diagnosis among immunocompromised patients was conducted by measuring quantitative CMV DNA polymerase chain reaction in plasma and bronchoalveolar lavage fluid (BALF). Forty-five adult immunocompromised patients were investigated. Thirty-two patients (71%) received immunosuppressive therapy. Eleven patients (24%) were confirmed to have CMVP. Of those, three and eight patients were classified as proven and probable CMVP, respectively. Median (IQR) plasma CMV DNA loads in CMVP and non-CMVP were 41,939 (4,424-122,608) and 0 (0-44) IU/mL, respectively (p<0.001). Median (IQR) BALF CMV DNA loads in CMVP and non-CMVP were 379,652 (163,800-1,254,000) and 0 (0-1,348) IU/mL, respectively (p<0.001). A significant correlation was observed between plasma and BALF CMV DNA loads (r=0.887, p<0.001). Plasma CMV DNA load of 831 IU/mL was established as a cut-off value for diagnosing CMVP (AUC 0.9987, sensitivity 100%, specificity 94.1%, positive predictive value 84.5%, negative predictive value 100%). A strongly positive correlation was observed between CMV DNA loads measured in plasma and BALF. CMV DNA load quantification could potentially assist in diagnosing CMVP in immunocompromised patients, although bronchoscopy remains encouraged for a definitive diagnosis.

CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients.

Cytomegalovirus colitis combined with Clostridium innocuum as a cause of lower GI bleeding in a patient with COVID-19

A 67-year-old woman who presented with fever received a diagnosis of COVID-19 infection and was admitted to the medicine ward. She had a history of hypertension and diabetes. On day 4 of hospitalization, owing to progressive dyspnea and oxygen desaturation, she received intubation and mechanical ventilator support. She received remdesivir, dexamethasone, empiric antibiotics, enoxaparin, and tocilizumab during her hospitalization. On day 24, the patient developed bloody stools, and her hemoglobin level decreased from 11.7 g/dL to 9.2 g/dL. Because of persistent bleeding, she underwent colonoscopy, which revealed colitis and ulcer bleeding at the rectum (A). CT showed wall thickening of the lower part of the rectum (B). A pathologic study of the biopsy specimen showed enlarged nuclei and viral inclusions in both the cytoplasm and the nuclei (C). Immunohistochemical stain was positive for cytomegalovirus (CMV) antigen (D). The result of a blood CMV DNA polymerase chain reaction was positive, and the diagnosis of CMV infection was confirmed. In addition, there was growth of Clostridium innocuum in the stool culture. Her bleeding subsided after ganciclovir and metronidazole treatment, and she was extubated smoothly on day 38. Here we illustrate a COVID-19 patient who presented with lower GI bleeding caused by CMV coinfection and growth of C innocuum simultaneously. Endoscopy plays a crucial role in the treatment of patients with GI bleeding. All authors disclosed no financial relationships. Commentary The healthier you are the healthier you stay; the sicker you are the sicker you get. This case reflects this axiom. This unfortunate patient experienced severe respiratory failure secondary to COVID-19 infection. Colonoscopy revealed a dramatic "punched out" ulcer, highly suggestive of a viral colitis, and indeed the patient was found to have a CMV infection. She was also found to harbor C innocuum, which, despite its name, should not be confused with C difficile. C innocuum is an anaerobic gram-positive rod that is considered to be a variant of normal gut flora. C innocuum usually behaves in a pathogenic manner in patients who are immunocompromised, as was clearly the case with this patient. C innocuum is often seen to cause illness in patients after organ transplantation, most commonly renal transplantation. Fortunately, this patient appears to have done well after aggressive therapy for her COVID-19 infection. Douglas G. Adler, MD, FASGE, GIE Senior Associate Editor, Co-Director, Center for Advanced Therapeutic Endoscopy (CATE), Porter Adventist Hospital, PEAK Gastroenterology, Denver, Colorado Mohamed O. Othman, MD, Associate Editor for Focal Points

Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant

Background :Reactivation of cytomegalovirus (CMV) commonly occurs post allogeneic stem cell transplant (ASCT). The incidence is at least 40-50% in India, where most patients and donors are CMV seropositive. Ganciclovir, although the drug of choice, is expensive and associated with significant toxicities. Second line agents like foscarnet and cidofovir are not available in India leaving few therapeutic options. Leflunomide, an anti rheumatoid arthritis drug, acts by inhibiting virion assembly of CMV and has been effective in post renal transplant CMV infections. This drug is inexpensive and has a favourable toxicity profile. There have been only occasional case reports of leflunomide post ASCT. Here we report the efficacy of leflunomide in CMV reactivation in ASCT setting.Methods :All patients who underwent ASCT at our centre between April 2015 and February 2017 were included in this retrospective study. Serologic evaluation for CMV infections was done at baseline for all patients and donors. Conditioning regimens used were either myeloablative [total body irradiation (TBI)-cyclophosphamide (Cy)] or reduced intensity (fludarabine with either melphalan, or Cy or treosulfan +/- 2 gray TBI). Graft versus host disease (GVHD) prophylaxis used was cyclosporine or tacrolimus with methotrexate or mycofenolate mofetil for matched sibling donor (MSD) and matched unrelated donor (MUD) transplants. Post transplant Cy was used for haplo-identical transplants (HIT).Monitoring was done twice weekly using quantitative CMV DNA polymerase chain reaction (QPCR) on peripheral blood post transplant till day +120 or longer if patient was on steroids. Patients who were detected to have a positive QPCR greater than 500 copies/mL at 2 consecutive time points were started on pre-emptive therapy. Ganciclovir was the preferred agent for pre-emptive therapy, however in case of ongoing cytopenias, leflunomide was used. In case of clinical resistance to ganciclovir, leflunomide was added as second line. Leflunomide was started at a loading dose of 100 mg once a day for 3 days followed by daily maintenance dose of 20 mg till clearance of CMV (undetectable CMV DNA on QPCR at 2 consecutive time points) or intolerance. Failure of leflunomide was defined as > 1 log increase in CMV copy number at any time or if another anti CMV agent was added due to CMV disease or non-clearance. Invasive procedures such as broncho-alveolar lavage, colonoscopic biopsies, and liver biopsies were used to detect CMV disease, when clinically suspected.Results :Seventy patients underwent ASCT during this period. This included 47 MSD transplants, 18 HIT and 5 MUD transplants. There were 49 episodes of CMV reactivation in 43 patients (61%). The incidence was highest in HIT with 17 of 18 patients developing reactivation.Leflunomide was used in 24 (49%) of the 49 episodes of CMV reactivations. It was used as 1st line agent in 15 episodes and as 2nd line in 9. The median CMV copy number/ml was 0.82x 103 (range 0 to 13x103) on day of starting leflunomide. The median duration of use was 34 days (range 6 to 85 days). It was used pre-emptively in 20 episodes and as therapeutic (i.e. patient had end organ involvement) in 4. None of the patients had toxicity requiring stopping of the drug. Nine (38%) of the 24 CMV reactivation episodes cleared with leflunomide. When used as a 1st line agent, CMV infection cleared in 7 of the 15 episodes (46%) in comparison to ganciclovir as 1st line with which 12 (52%) of 23 episodes cleared.Seven of the 24 episodes had initial CMV burden more than 2 x 103 copies/mL. Leflunomide failed in all of these, as against clearance in 9 of the 17 episodes which had CMV less than 2 x 103 copies/mL. (p= 0.022). None of the patients who received leflunomide in therapeutic setting cleared CMV (0 of 4), compared to 9 of 20 with pre-emptive leflunomide. (p= NS).Conclusions:This is the largest study of using leflunomide for CMV reactivation in post ASCT setting to our knowledge. Leflunomide has considerable activity against CMV, however it is best used when CMV copies are less than 2000 /mL in pre-emptive setting. In therapeutic setting its role seems limited. A larger prospective study is warranted. DisclosuresNo relevant conflicts of interest to declare.

Unexpected Cytomegalovirus (CMV) Replication Kinetics in CMV Donor-Seropositive, Recipient-Seronegative Liver Transplant Recipients Receiving Preemptive Antiviral Therapy.

Detailed cytomegalovirus (CMV) kinetics in donor CMV-seropositive, recipient CMV-seronegative (D+/R-) transplant recipients receiving preemptive therapy (PET) have not been fully defined. The study population consisted of the PET arm of a randomized CMV prevention trial in D+/R- liver transplant recipients. CMV DNA polymerase chain reaction (PCR) assays were performed weekly for 100 days using a sensitive assay. Viral load and clinical parameters were compared for patients with or without high-level increase (defined as higher than the group median log10 increase in viral load from baseline after PET initiation). Among 79 patients, 93.6% (74/79) developed an increase from baseline viral loads of median 120 IU/mL to 3350 IU/mL; 25.7% (19/74) of the patients had peak levels >10 000 IU/mL. None of the patients with rise in viral load underwent testing for CMV resistance, and viremia resolved with PET with valganciclovir. Patients with high-level increase in viral load had a significantly lower rate of recurrent viremia than those without such increase (16/40 [40%] vs 28/39 [71.8%], respectively; P = .004). A majority of D+/R- recipients had a marked increase in viral load after initiation of PET before resolution of viremia. This phenomenon is associated with lower rates of subsequent recurrent viremia and does not necessarily imply antiviral resistance.

Epidemiology of cytomegalovirus Infection among mothers and infants in Colombia.

We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection.

Spontaneously-resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes.

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 patients, of which 144 episodes cleared spontaneously. Clearance of CMV DNAemia was significantly delayed in initial and recurrent self-resolving episodes featuring CMV DNA peak loads > 250 IU/mL compared with those displaying lower values. All-cause mortality in patients with self-resolving episodes of CMV DNAemia was comparable (P = 0.7) to that in patients with no CMV DNAemia and was not related to the CMV DNA peak load (≥250 IU/mL vs <250 IU/mL) (P = 0.6). In summary, in our setting, the magnitude of the CMV DNA peak load reached during self-resolving episodes of CMV DNAemia correlated directly with duration of episodes, but had no apparent impact on all-cause mortality taking patients with no documented CMV DNAemia as a reference.

Cytomegalovirus (CMV) Pentameric Complex (PC) Neutralizing Antibodies (nAb) from a Randomized, Controlled Trial of CMV-Specific Intravenous Immunoglobulin (IVIG) for the Prevention of Primary CMV Infection after Hematopoietic Cell Transplantation (HCT)

Prevention of CMV disease after HCT remains a challenge. In addition to antivirals, immune-based strategies such as active and passive immunization may have potential roles preventing infection. CMV entry into epithelial and endothelial cells requires distinct viral proteins including UL128, UL130, UL131A, gB and gH/gL that combine to form a PC. A nAb assay was developed by Gerna et al. that measures nAb activity against PC, although its clinical application in HCT patients has not been described. In 1991, Bowden et al. conducted a study where CMV IVIG was administered as prophylaxis to D+/R- patients early after allogenic HCT. Although it showed reduced CMV infection in CMV IVIG recipients, CMV disease was not reduced thus its use was never adopted. This impact on infection suggests the possibility that CMV IVIG inhibits infection via neutralization of an unidentified entry pathway that may include PC. From the original cohort, we tested 538 serum samples from 61 patients using CMV DNA polymerase chain reaction (PCR) to compare clinically significant viral load (≥ 4 log10 IU/ml) or histopathologically detected CMV between groups. We also used a CMV nAb assay to evaluate anti-PC neutralizing capacity. The assay uses retinal pigmented epithelial (ARPE-19) cells exposed to serial dilutions of serum combined with a laboratory CMV strain, BADrUL131-Y4, that contains a green fluorescent protein (GFP) cassette. After one hour incubation, cells are washed and incubated for one week. Fluorescence is measured and we construct curves that plot viral neutralization against serum dilution and from these we extrapolate an IC-50; that is the dilution where 50% virus neutralization is achieved. After excluding three patients infected prior to day 21 post-transplant, there were 27 CMV IVIG and 31 control patients. Neither cumulative incidence of CMV infection (Figure 1, p=0.55), nor IC-50 values (Figure 2, p=0.19) differed by study arm, though observed median IC-50 values were higher in the CMV IVIG arm (5.8) than in the control arm (4.8). We found no association between IC-50 and risk of CMV infection (HR=1.8, 95% CI 0.6-5.3, p=0.31). Using modern CMV detection methods, our study suggests CMV IVIG does not result in decreased CMV viral load. Although the PC nAb composition of the CMV IVIG used is unknown, it did not appear protective against CMV infection. We successfully evaluated CMV PC entry-specific neutralizing activity in the HCT setting using a nAb assay, however evaluation among larger cohorts is needed to determine its clinical utility.

Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy.

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in the posttransplant setting; however, it is increasingly recognized in pediatric leukemia during chemotherapy. This study assessed the prevalence and associated factors of CMV infection in pediatric non-transplant leukemia patients.This was a cross-sectional study of 50 pediatric acute lymphoblastic leukemia (ALL) patients receiving chemotherapy at Ramathibodi Hospital from December 2015 to December 2016. CMV viral load quantified by DNA polymerase chain reaction (PCR) was monitored in different phases of chemotherapy: enrolment, post-induction, post-consolidation, post-intensification, and maintenance.One hundred forty one blood tests were evaluated from 50 patients. Overall prevalence of CMV DNAemia (≥20 copies/mL) and high-level CMV DNAemia (≥1000 copies/mL) was 52% (26 of 50) and 16.0% (8 of 50), respectively. All patients with high-level CMV DNAemia were in the maintenance phase of chemotherapy. One patient had CMV retinitis, while the rest had no end-organ CMV diseases. Increased lymphocyte count was significantly associated with protection from high-level CMV DNAemia (odds ratio 0.997, P = .02). Receiver operating characteristic curve identified a cut-off value of 798 cells/mm3 of absolute lymphocyte count (ALC) as a discriminator for the presence of high-level CMV DNAemia (area under the curve 0.756, 95% CI 0.645–0.867, P = .001) with 88.9% sensitivity and 50.4% specificity.CMV infection predominantly occurred during maintenance chemotherapy. Low ALC was significantly associated with high-level CMV DNAemia. CMV infection surveillance by quantitative CMV DNA PCR during maintenance chemotherapy in patients with ALC <800 cells/mm3 may be considered.

Diagnostic utility of quantitative cytomegalovirus DNA polymerase chain reaction in intestinal biopsies from patients with inflammatory bowel disease.

OBJECTIVES:Diagnostic utility of cytomegalovirus (CMV) DNA quantitative polymerase chain reaction (qPCR) in inflammatory bowel disease (IBD) has not been established. We aimed to compare diagnostic utility of qPCR for CMV in biopsy specimens with blood, serology, and histopathology.MATERIALS AND METHODS:A total of 132 patients were included (92 ulcerative colitis [UC], 9 Crohn's disease, and 31 unclassified IBD). Comparison between CMV IgM, CMV DNA qPCR in biopsy, in blood and histopathology was done. Positive result in any of the test was considered as CMV infection. Various risk factors for CMV association with IBD were analyzed.RESULTS:Confirmed CMV infection was seen in 41 (31.1%) patients. Diagnostic sensitivity of different assays was: DNA in biopsy seen in 37 (90.2%), DNA in blood in 19 (46.3%), CMV IgM in 15 (36.5%), and histopathology in 8 (19.5%). Thirty-two UC cases were further followed up for a median time of 14.0 (R: 3–31) months. They were grouped as group I – biopsy and blood DNA both positive (14, 43.7%), Group II – biopsy positive and blood negative (17, 53.1%), and Group III – biopsy negative but blood positive (1, 3.1%). CMV DNA viral load in Group I was significantly higher (mean: 4.2 ± 1.0 log10 copies/mg) than Group II (mean: 3.2 ± 0.6 copies/mg) and Group III (viral load: 2.69 log10 copies/ml), P < 0.001. Steroid refractoriness was seen more in Group I cases (n = 9) P < 0.001. A cutoff of ≥2.5 log10 copies/mg of DNA in tissue was predictive for steroid refractoriness (AUROC = 0.84).CONCLUSIONS:Quantitation of CMV DNA in intestinal biopsy is a useful diagnostic tool and can predict response to steroid treatment in patients with UC.

The significance of cytomegalovirus in children with pneumonia admitted for mechanical ventilation.

The pathogenic role of cytomegalovirus (CMV) among children with pneumonia is not clear. We describe the outcome of children on mechanical ventilation with 'probable' CMV-related pneumonitis (CMV DNA polymerase chain reaction [PCR] positive as well as clinical and imaging features of CMV on ganciclovir) and children with pneumonia and CMV infection (CMV DNA PCR-positive without clinical and imaging features of CMV and not on ganciclovir therapy) at a paediatric intensive care unit in South Africa between 2011 and 2013. CMV viral loads were measured in non-bronchoscopic bronchoalveolar lavage fluid (NBBALF), plasma and whole-blood samples. Of the 97 children enrolled, 38 had CMV-related pneumonitis, 27 had pneumonia and CMV infection and 32 had pneumonia without CMV infection (negative CMV DNA PCR). Survival in the three groups was respectively 73.7% (P < 0.05), 92.6% (P < 0.05) and 88.0%. The difference in outcome could be accounted for by variance in the prevalence of human immunodeficiency virus (HIV) infection (respectively 60.5% and 29.6%, P < 0.05). A higher CMV viral load in NBBALF and plasma was seen in cases of CMV-related pneumonitis than in pneumonia with CMV infection: respectively log 5.20 vs. log 4.10 (P < 0.05) and 4.56 vs. 3.47 (P < 0.05). HIV-infected children on mechanical ventilation with CMV-related pneumonitis on ganciclovir have poor outcomes. Randomised placebo-controlled studies on ganciclovir are required.

Cytomegalovirus infection in the bone marrow transplant patient.

Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.

A Rare Complication of Cytomegalovirus Infection

Immune recovery uveitis is a type of immune reconstitution inflammatory syndrome (IRIS) associated with cytomegalovirus (CMV) that is well described, however there are very few reports of extraocular CMV–associated central nervous system IRIS clinical manifestations. A 35-year-old human immunodeficiency virus–infected woman receiving antiretroviral therapy for 7 weeks and ganciclovir for 3 months for CMV retinitis presented with a 1-week history of varied neurologic complaints. Since initiating the antiretroviral therapy, she had more than a 4-fold increase in CD4+ count and a 1-log reduction in human immunodeficiency virus viral load. Magnetic resonance imaging showed enhancement of the ventricles and leptomeninges. Cytomegalovirus DNA polymerase chain reaction confirmed the presence of CMV in the cerebrospinal fluid, consistent with a diagnosis of CMV meningoventriculoencephalitis IRIS. Extraocular CMV–associated central nervous system IRIS is exceedingly rare and its clinical presentation seems variable. This report demonstrates successful management with the addition of corticosteroids to anti-CMV therapy with prompt neurological improvement.

Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis

Background and aimsClinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. MethodsMedical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. ResultsOf the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). ConclusionsAlthough CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.

Cytomegalovirus Retinitis in Chinese Patients of non-Hodgkin Lymphoma with Normal CD4 Counts

Objective: To manifested the clinic features in two cases of cytomegalovirus(CMV) retinitis in Chinese patients of non-Hodgkin lymphoma with normal CD4 counts. Methods: Two patients with non-Hodgkin lymphoma presented with floaters and vision reduction in affected eyes. The patient underwent eye examination and blood investigation, and vitreous was extracted for CMV-DNA polymerase chain reaction (PCR). The patient was treated with intravenous and intravitreal ganciclovir. Results: Funduscopy showed typical yellow and white lesions in the retina of affected eyes. Blood investigation showed HIV(-), CMV- IgG (+) IgM (-),and CD4 T-cell counts more than 300 cells/ul. CMV DNA PCR(+) of vitreous sample supported the diagnosis of CMV retinitis. Retinitis regressed after the treatment of ganciclovir. Conclusions: CMV retinitis occurred in non-HIV disease such as non-Hodgkin lymphoma with normal CD4 counts. These cases showed CMV-DNA PCR of vitreous may be a good marker for CMV retinitis and intravitreal ganciclovir may be an effective treatment.

Prevalence of congenital cytomegalovirus infection in Slovenia: A study on 2,841 newborns

Human cytomegalovirus (CMV) is the most frequent cause of congenital infection in humans. In the first prevalence study of congenital CMV infection in Eastern and Central Europe, all neonates born in a 22-month period in two Slovenian maternity units (total of 2,841 newborns) were screened prospectively for congenital CMV infection by a real-time polymerase chain reaction (PCR) in urine. In all newborns with positive screening results, plasma and dried blood spots (DBS) collected at birth were tested additionally for CMV DNA. Congenital CMV infection was confirmed by virus isolation from a urine sample collected within the first 2 weeks of life. Congenital CMV infection was identified in four out of 2,841 newborns tested (incidence 0.14%; 95% CI, 0.05-0.39%). In four newborns with confirmed congenital infection, the concentration of CMV DNA in urine ranged from 4.68 to 8.18 log(10) copies/ml, all four newborns had detectable CMV DNA in plasma taken at birth (1.26-3.34 log(10) copies/ml) and two out of four had detectable CMV DNA in DBS collected during newborn metabolic screening. None of the four newborns with confirmed congenital CMV infection was symptomatic. The study showed that the prevalence of congenital CMV infection at birth in Slovenia is among the lowest in the world and that CMV DNA PCR testing of urine is a suitable and affordable real-time screening strategy for congenital CMV infection. If it is performed in 24 mini-pools, the cost of screening is 1.4 €/newborn and the cost of detecting a single newborn with congenital CMV infection 1,000 €.

Cytomegalovirus viraemia in the modern antiretroviral era*

Cytomegalovirus viraemia in the modern antiretroviral era*

Cytomegalovirus ileitis in a patient after liver transplantation-differentiating from de novo IBD

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract has been reported in immunocompromised patients and is seen following liver transplantation. Although CMV infection can affect any part of the GI tract, involvement of the terminal ileum is rarely encountered after liver transplantation. We report a case of a 32-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for liver transplantation. Initial ganciclovir treatment did not improve the patient's symptoms and therapy was then switched to foscarnet which ultimately resulted in resolution of infection. However the patient continued to have symptoms because of intermittent small bowel obstruction because of ulcerations and fibrosis ultimately requiring surgical resection. CMV DNA polymerase chain reaction (PCR) was negative throughout the course of infection. Surgical resected specimen revealed no evidence of inflammatory bowel disease (IBD). Follow up colonoscopy up to a year after infection also did not reveal any evidence of IBD. Compartmentalization in the clinical presentation of CMV involving GI tract can be seen with a negative blood DNA PCR. Histological diagnosis thus forms an important part in the clinical follow-up of liver transplant patients undergoing intense immunosuppression and should be aggressively pursued in patients with GI symptoms. De novo IBD should be considered in the differential diagnosis in these patients who do not improve with anti-viral treatment.

The validity of clinical feature profiles for cytomegaloviral anterior segment infection

Anterior segment cytomegalovirus (CMV) infection, which can be presented as anterior uveitis and corneal endotheliitis, has recently been reported in immunocompetent patients. We would like to access the validity of two presumed characteristic clinical profiles: profile 1, non-herpes simplex virus (HSV)/varicella zoster virus (VZV) corticosteroid-recalcitrant inflammatory ocular hypertensive syndrome (IOHS), and profile 2, corneal endotheliitis with specific coin-shaped keratic precipitates (KPs), that could be helpful in identifying CMV anterior segment intraocular infection. Patients with either profile 1 or profile 2 or both were enrolled consecutively from the uveitis service in Chang Gung Memorial Hospital, Taoyuan, between January 1, 2006 and May 31, 2010. Diagnostic anterior chamber tapping was performed and followed by real-time quantitative polymerase chain reaction (PCR) to detect herpesviridae DNA including HSV I and II, VZV, CMV, and Epstein-Barr virus. Thirty-one eyes of 30 patients (21 males and nine females) were enrolled in this study. CMV DNA PCR was positive in 29 eyes of 28 patients (20 males and eight females). Nineteen of 20 eyes (19 patients) in profile 1 had positive CMV PCR. Ten of 11 eyes (11 patients) in profile 2 had positive CMV PCR. The positive predictive value of profile 1 and profile 2 was 94.7% and 90.9%, respectively. The positive predictive value of combining the two profiles was 93.3%. Non-HSV/ZVZ corticosteroid-recalcitrant IOHS and corneal endotheliitis with specific coin-shaped KPs could be used as the screening tool for CMV anterior segment intraocular infection.