Severe cytomegalovirus encephalitis in an immunocompetent man: a case report

Cytomegalovirus Infection

Human Cytomegalovirus and Kidney Transplantation: A Clinician's Update

AIDS-related cytomegalovirus (CMV) encephalitis has declined in the combined antiretroviral therapy (ART) era in high-income countries. However, there is scarce information on CMV encephalitis in low- and middle-income countries. The objectives of this study were to identify the prevalence of AIDS-related CMV encephalitis and describe its main features. This was a retrospective cohort study carried out at a referral center in São Paulo, Brazil. We included adult people living with HIV/AIDS (PLWHA), hospitalized in 2019, with a CD4 cell count ≤100/mm3 and quantitation CMV DNA results in plasma. Cases with compatible neurological manifestations and detection of CMV DNA by polymerase chain reaction (PCR) in cerebrospinal fluid samples were defined as CMV encephalitis. Among 761 PLWHA hospitalized, 248 (32.5%) cases were included in this study. Prevalence of CMV encephalitis was 2.4% (6/248) among all included cases and 7.7% (6/78) among individuals with neurological opportunistic diseases. The six patients with CMV encephalitis were males and had CD4 cell count <50/mm3. Five (83%) cases had CMV encephalitis as AIDS-defining disease and showed CMV DNA detection by PCR >50,000UI/mL plasma. All six cases received anti-CMV therapy (ganciclovir, n = 4; ganciclovir plus foscarnet, n = 2) and five were discharged to home. CMV encephalitis was not uncommon among hospitalized PLWHA with neurological opportunistic diseases. The epidemiological and immunological profile of individuals with CMV encephalitis was similar to that described in the pre-ART era, but in contrast, most cases were treated and discharged from the hospital.

Detection of cytomegalovirus (CMV) DNA by the polymerase chain reaction (PCR) in samples of cerebrospinal fluid (CSF) has been shown to be a sensitive method of diagnosing CMV disease in the central nervous system. Since CMV causes latent infection in white blood cells, an unanswered question is whether detection of latent CMV DNA in the cell fraction of CSF samples by PCR is possible in seropositive patients. In a prospective study, the finding of CMV DNA in CSF of CMV seropositive patients with suspected viral infection of the central nervous system (CNS) was evaluated clinically. Fractionation of 64 CSF samples from seropositive patients was carried out before analysing the samples for CMV DNA by PCR. In four of the five patients who had CMV DNA in the cell pellet and/or supernatant, the clinical data suggested CMV-associated neurological disease. The remaining 59 samples were negative in both pellet and supernatant. In addition, 11 CSF samples with high cell counts from patients with bacterial meningitis were examined for CMV DNA and found to be negative in 10 patients and positive in 1. One hundred thirty two uncentrifuged CSF samples were used as negative controls. The results of the study indicate that detection of CMV DNA in CSF samples by PCR correlated well with disease and was not due to latent CMV infection.

Cytomegalovirus Identification and Quantification from the Saliva of Human Immunodeficiency Virus Seropositive and Seronegative Patients Using Real Time Polymerase Chain Reaction

Detection of herpesvirus genomes by polymerase chain reaction in cerebrospinal fluid and clinical findings.

Human cytomegalovirus infection of cells of hematopoietic origin: HCMV-induced immunosuppression, immune evasion, and latency

BackgroundCytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported.Case presentationWe report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient’s clinical history.ConclusionDifferent risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.

Cytomegalovirus (CMV) is a common opportunistic pathogen infecting AIDS patients. Polymerase chain reaction (PCR) and antigen capture ELISA were used to detect CMV in 40 cerebrospinal fluid autopsy specimens from patients with AIDS. CMV DNA was detected by PCR in 70% of samples. Of the 21 samples from patients with systemic CMV infection, 57% had CMV encephalitis, while 81% had virus in cerebrospinal fluid detectable by PCR. Of the 24 samples from patients with no histologic evidence of CMV encephalitis, 58% had CMV DNA in cerebrospinal fluid detected by PCR. These results suggest that PCR of cerebrospinal fluid sensitively detects systemic CMV infection but is not specific for brain infection in autopsy specimens of AIDS patients.

Cytomegalovirus (CMV) infection can cause severe pulmonary disease in immunocompromised patients. There are no standard diagnostic criteria for CMV pulmonary disease beyond histopathology findings on lung tissue, which is challenging to obtain in pediatric patients. Bronchoalveolar lavage (BAL) fluid is easier to obtain. Since CMV remains latent after primary infection and can potentially reactivate due to any inflammatory response, CMV detection in BAL specimen may not indicate acute CMV pulmonary disease. Thus, we describe the clinical manifestations and outcomes of pediatric patients with CMV detection in BAL fluid. We reviewed the clinical, radiologic, and laboratory data of patients <19 years old with a BAL specimen positive for CMV during a 5-year period. Thirty-four encounters in 29 patients were found with CMV detected in their BAL specimen. Half (17/34) of the encounters were in immunocompromised patients. CMV, polymerase chain reaction (PCR) was the most common positive test. Forty-seven percent of the patients had other infections detected in BAL specimens. The majority of patients were never treated for CMV and resolved their acute respiratory illness. Only one patient had probable CMV pulmonary disease. CMV is frequently recovered from BAL specimens but does not usually indicate acute CMV pulmonary disease. We would suggest that other diagnoses be considered first, even if CMV is recovered. Pediatr Pulmonol. 2017;52:112-118. © 2016 Wiley Periodicals, Inc.

Cytomegalovirus-induced cutaneous vasculopathy and perianal ulceration

The CARI guidelines. CMV disease and kidney transplant: treatment of cytomegalovirus disease in renal transplant recipients.

Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are vulnerable to opportunistic infections, including cytomegalovirus (CMV) infection. This narrative review aims to identify factors associated with CMV infection in patients with AAV. The literature review was conducted on Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, PubMed, Scopus, and Web of Science. The start date of the literature search was unrestricted and the end date was February 2022. CMV infection was defined as (a) CMV pp65 antigenemia or positive CMV DNA viral load by polymerase chain reaction or CMV detection on histological specimens, with associated signs and symptoms compatible with CMV infection; (b) presence of CMV clinical syndrome (defined as presence of compatible symptoms and signs and documentation of CMV by biopsy by virus isolation, rapid culture, immunohistochemistry, or DNA in biopsy material as defined by the CMV Drug Development Forum); and (c) CMV infection as coded by the International Statistical Classification of Diseases and Related Health Problems, 10th revision with at least one prescription for CMV treatment. We identified 4505 articles, of which three (2327 patients with AAV) were included. All studies were retrospective and only one of the three studies included only patients with AAV. Low or decreasing lymphocyte counts and higher prednisolone usage were associated with CMV infection in patients with AAV. Patients with AAV with lymphopenia and on high doses of prednisolone should be monitored closely for signs and symptoms of CMV infection, and might benefit from CMV prophylaxis. Prospective studies are urgently needed to better identify causes of CMV infections in patients with AAV.

Seventy-five organ transplant recipients underwent prolonged virological and serological follow-up for early detection of human cytomegalovirus (HCMV) infection after transplantation. HCMV DNA detection by nested polymerase chain reaction (PCR) and HCMV early structural antigen (pp65) detection were carried out in 576 peripheral blood leucocyte (PBL) samples. Furthermore, 563 blood specimens were investigated by a commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of specific immunoglobulins G, M, and A against HCMV structural antigens. In eight of nine symptomatic organ transplant recipients, HCMV DNA was detected in one or more consecutive blood samples. HCMV DNA PCR was also positive in one or more samples from eight patients who never developed HCMV-related symptoms. HCMV pp65 antigen was detected almost exclusively in PBL samples from organ transplant recipients suffering from HCMV disease. However, antigenaemia was not detected in four PCR positive patients presenting clinical signs attributable to HCMV infection. Two of the initially HCMV DNA positive samples were not confirmed by retesting and hybridisation. The results of the present study demonstrate that despite the high specificity of nested PCR, HCMV DNA may be detected in the absence of clinical symptoms attributable to HCMV infection. In asymptomatic reactivation, limited replication of viral DNA may be responsible for positive results of PCR without any clinical relevance. In this context, pp65-antigen detection from PBL seems to have a better prognostic value, but is not always detected when clinical symptoms are present.

Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted patients is still controversial. A prospective study of CMV detection, with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp fragment in the Us region and a 290-bp fragment in the immediate early region of the viral genome. When comparing PCR to viral culture, the sensitivity and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and 100% and 75% in BAL (n=104). The positive and negative predictive values of PCR for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67% and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment: when PCR was still positive either in blood or BAL, CMV infection relapsed within 35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days (P=0.01). Negative CMV detection by PCR strongly advocates against a forthcoming CMV infection. PCR assay seems to be a good predictor for early recurrence of CMV infection, and would be useful for monitoring the response to antiviral therapy.