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Cureus Sep 2023Cytomegalovirus (CMV) can present with end-organ disease (EOD), particularly in patients with a CD4 cell count <50/mm. While EOD in immunocompromised patients commonly...
Cytomegalovirus (CMV) can present with end-organ disease (EOD), particularly in patients with a CD4 cell count <50/mm. While EOD in immunocompromised patients commonly presents as CMV retinitis (30%) and CMV colitis (5-10%), CMV esophagitis is rare. CMV is the third most common infectious esophagitis following Candida and Herpes Simplex. CMV esophagitis presents with odynophagia, dysphagia, and abdominal pain. Endoscopic exam may reveal large, linear distal esophageal ulcers. Histopathology or serology studies are diagnostic, though serology may be unreliable in the extremely immunosuppressed. Current treatment consists of antivirals such as ganciclovir and valganciclovir. Esophageal disease due to CMV carries a poor prognosis in the immunocompromised. We present the case of a 56-year-old male with a medical history of HIV/AIDS and stage III rectal squamous cell cancer who presented with shortness of breath, weakness, and chronic diarrhea. His HIV was previously well-controlled on antiretroviral therapy. However, due to his malignancy, he was undergoing treatment with chemotherapy and radiation. Initial labs revealed a CD4 count of 42. His clinical course consisted of septicemia, new-onset atrial fibrillation with a rapid ventricular response, worsening pneumonia, possible metastasis, progressive diarrhea, and potential oropharyngeal candidiasis. Despite several broad-spectrum antimicrobial regimens, he remained symptomatic with new complaints of dysphagia and odynophagia. Eventually, the appearance of vesicular lesions on the lips and a repeat CD4 count of 13 garnered a suspicion of HSV or CMV. This complicated case highlights the necessity for a high index of suspicion of rare manifestations of CMV EOD in an immunocompromised patient presenting with confounding clinical symptoms and extensive diagnoses.
PubMed: 37868477
DOI: 10.7759/cureus.45634 -
Cureus Sep 2023Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that results in inflammation and ulceration in the lining of the large intestine. Patients with UC are...
Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that results in inflammation and ulceration in the lining of the large intestine. Patients with UC are frequently prescribed immunosuppressive medications to treat their symptoms, resulting in an increased risk of reactivation of many latent viruses, including herpes simplex virus (HSV) and cytomegalovirus (CMV). However, it is rare for a patient to present with simultaneous reactivation of both viruses. Here, we document the presentation, hospital course, and clinical findings of a UC patient with HSV and CMV dual infection. We also describe treatment strategies and prophylactic measures for managing a dual infection. This is seen through initiating valganciclovir in the outpatient setting following the diagnosis.
PubMed: 37842466
DOI: 10.7759/cureus.45166 -
Cureus Aug 2023Gastrointestinal (GI) cytomegalovirus (CMV) infections are far more common in immunocompromised as opposed to immunocompetent patients. Immunocompetent patients who...
Gastrointestinal (GI) cytomegalovirus (CMV) infections are far more common in immunocompromised as opposed to immunocompetent patients. Immunocompetent patients who develop GI tract CMV infections are typically older with medical comorbidities. As such, descriptions of GI CMV infections in younger immunocompetent patients are lacking. Here, we present a case of a GI CMV infection in a young and healthy immunocompetent patient. A 41-year-old male with hyperlipidemia and hypothyroidism presented with painless, intermittent hematochezia. He denied changes in bowel habits or appetite, abdominal pain, fevers, chills, fatigue, or weight loss. His history was pertinent for insertive and receptive intercourse with one male partner. Medications were emtricitabine/tenofovir for pre-exposure prophylaxis, levothyroxine, and atorvastatin. A colonoscopy revealed a cecal ulcer surrounded by nodular-appearing mucosa that felt firm and friable when biopsied. The remaining colon and terminal ileum were normal. There was no diverticulosis or hemorrhoids. Pathology was positive for CMV. A subsequent serological evaluation revealed a normal complete blood count and comprehensive metabolic panel. Tests for human immunodeficiency virus, syphilis, viral hepatitis, chlamydia, and gonorrhea were negative. He was treated with valganciclovir 900 mg twice daily for 21 days. A subsequent test for CMV deoxyribonucleic acid polymerase chain was negative. Hematochezia resolved. A repeat colonoscopy revealed normal mucosa in the cecum. GI CMV infections in immunocompetent patients are rare and typically occur in older patients with medical comorbidities. Further, such case reports are needed to inform clinicians about risk factors and the presentation of GI CMV infections in young healthy immunocompetent patients.
PubMed: 37772223
DOI: 10.7759/cureus.44274 -
Clinical Infectious Diseases : An... Feb 2024The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. (Randomized Controlled Trial)
Randomized Controlled Trial
Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.
BACKGROUND
The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation.
METHODS
In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus.
RESULTS
Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001).
CONCLUSIONS
Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection.
CLINICAL TRIALS REGISTRATION
NCT02538172.
Topics: Humans; Cytomegalovirus; Antiviral Agents; Monitoring, Immunologic; Cytomegalovirus Infections; Transplant Recipients; Organ Transplantation; Ganciclovir
PubMed: 37738676
DOI: 10.1093/cid/ciad575 -
Cureus Aug 2023Cytomegalovirus (CMV) is one of the most frequent microbes linked with kidney transplant recipients. CMV infection is typically classified as CMV virus isolation in any...
Cytomegalovirus (CMV) is one of the most frequent microbes linked with kidney transplant recipients. CMV infection is typically classified as CMV virus isolation in any body fluid or specimen. We present a 43-year-old man who underwent a deceased donor kidney transplant with CMV donor-seronegative and recipient-seronegative (CMV D-/R-) status and completed three months of CMV prophylaxis with high-dose acyclovir given his low-risk status. He was admitted for complaints of profuse watery diarrhea and persistent fevers lasting one week in duration. His infectious workup led to a CMV quantitative nucleic acid amplification test (QNAT) polymerase chain reaction (PCR) of 239,977 IU/mL with a biopsy-proven diagnosis of invasive CMV colitis. He was treated inpatient with intravenous ganciclovir for two weeks and then de-escalated to oral valganciclovir until achieving viremia resolution with undetectable CMV QNAT PCR as an outpatient. This case illustrates the importance of the changing epidemiology and clinical presentation of CMV disease in solid organ transplant (SOT) recipients in an era of new immunosuppression regimens and improved CMV disease detection in the early post-transplant period.
PubMed: 37719577
DOI: 10.7759/cureus.43509 -
PloS One 2023In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was...
In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.
Topics: Humans; Male; Adenocarcinoma; Adenoviridae; Genetic Therapy; Interleukin-12; Leukocytes, Mononuclear; Prostate; Prostatic Neoplasms; Genes, Transgenic, Suicide; Oncolytic Virotherapy
PubMed: 37713401
DOI: 10.1371/journal.pone.0291315 -
Le Infezioni in Medicina 2023cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and...
BACKGROUND
cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/μL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed.
RESULTS
the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for , while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement.
CONCLUSIONS
despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).
PubMed: 37701378
DOI: 10.53854/liim-3103-15 -
Journal of Korean Medical Science Aug 2023The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a...
BACKGROUND
The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery.
METHODS
This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated.
RESULTS
The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6-40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir.
CONCLUSION
Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; Child; Valganciclovir; Retrospective Studies; Placenta; Cytomegalovirus Infections; Ganciclovir; Antiviral Agents; Hearing Loss; Fetal Growth Retardation; Parturition; Immunoglobulin M
PubMed: 37582499
DOI: 10.3346/jkms.2023.38.e249 -
International Journal of Molecular... Jul 2023Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor...
Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.
Topics: Alcoholism; Stem Cells; Male; Female; Animals; Rats; Ethanol; Drug-Seeking Behavior; Behavior, Animal; Aging; Valganciclovir; Sex Characteristics; Humans; Rats, Transgenic
PubMed: 37569609
DOI: 10.3390/ijms241512233 -
Ear and HearingCongenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of...
Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.
OBJECTIVES
Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy.
DESIGN
The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic. Chart review identified infants with cCMV, and records were reviewed for information about universal newborn hearing screen (UNHS) results, the clinical course of SNHL, and the use of antiviral therapy.
RESULTS
A total of 44 children were identified with cCMV. In this group, 33 (75%) had SNHL of varying degree and age at onset. Notably, 17 (39%) children passed UNHS bilaterally. Of those children, 6 (35%) ultimately acquired bilateral or unilateral SNHL, detected at a mean age of 20 months (median age, 12 months). Five out of 10 children (50%) that did not pass UNHS in one ear acquired late-onset hearing loss in the contralateral ear, identified at a mean age of 24 months (median age, 4 months). Eleven (25%) children passed UNHS bilaterally and continued to demonstrate normal hearing in both ears at their most recent follow-up visit at a mean age of 19 months (SD, 18 months). Of the 33 children with cCMV and SNHL, 18 (55%) received antiviral medication (ganciclovir and/or valganciclovir). While, on average, both treated and untreated ears experienced a progression of hearing loss over time, the group that received antiviral treatment experienced less overall hearing change compared with the untreated group (baseline-adjusted expected mean difference, -10.5 dB; 95% confidence interval, -28.1 to 7.2 dB).
CONCLUSIONS
Among children with cCMV included in this study who passed UNHS in both ears, 35% demonstrated delayed-onset SNHL. Notably, of those children who referred unilaterally, 50% later demonstrated SNHL in the contralateral ear. These findings have implications for audiological monitoring, and potentially antiviral therapy, of children with cCMV. As implementation of universal cCMV screening moves forward, a key aspect of follow-up will be appropriate long-term audiologic monitoring.
Topics: Infant; Infant, Newborn; Humans; Child; Child, Preschool; Cytomegalovirus; Retrospective Studies; Hearing Loss, Sensorineural; Hearing; Cytomegalovirus Infections; Deafness; Antiviral Agents; Neonatal Screening
PubMed: 37563758
DOI: 10.1097/AUD.0000000000001411