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Tropical Medicine and Infectious Disease Dec 2022Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for... (Review)
Review
Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated.
PubMed: 36548694
DOI: 10.3390/tropicalmed7120439 -
Cureus Nov 2022Infections after renal transplant are a common cause of morbidity and are commonly due to Cytomegalovirus (CMV), , , and . Concurrent infections with both cryptococcal...
Infections after renal transplant are a common cause of morbidity and are commonly due to Cytomegalovirus (CMV), , , and . Concurrent infections with both cryptococcal and tuberculous aetiologies are rare within the central nervous system (CNS). We present a case of a 67-year-old male patient who presented with three weeks of headaches, confusion, unsteady gait, and seizures. He had type 2 diabetes mellitus and hypertension. He had a kidney transplant three years prior and was on three immunosuppressive agents. He was HIV-negative. He was evaluated and found to have cryptococcal meningitis and received appropriate treatment with liposomal amphotericin B, flucytosine, and serial lumbar punctures. He also had treatment for CMV viremia with valganciclovir. Three weeks later, after an initial good clinical response, he deteriorated with worsening confusion and persistent seizures. We re-evaluated him and found him to have brain imaging suggestive of tuberculosis. We started him on anti-tuberculous medication, and he improved significantly and was alert and seizure free at discharge home one month later. This case highlights that concurrent CNS infections with cryptococcus and tuberculosis do occur especially in patients who are severely immunosuppressed such as after a renal transplant. Failure to improve while on treatment for one CNS opportunistic infection should prompt one to investigate for other concurrent causes.
PubMed: 36475153
DOI: 10.7759/cureus.31012 -
Current Treatment Options in Pediatrics 2022There have been recent advances in the field of congenital CMV infection (cCMV) related to antiviral treatment of pregnant women and infants, the implementation of... (Review)
Review
PURPOSE OF REVIEW
There have been recent advances in the field of congenital CMV infection (cCMV) related to antiviral treatment of pregnant women and infants, the implementation of newborn CMV screening programs, and the frequency and diagnosis of complications among infected children. In addition, postnatal CMV infection (pCMV) is increasingly recognized as a potential cause of long-term sequelae in addition to acute complications among preterm infants, raising important questions related to treatment, and prevention.
RECENT FINDINGS
High-dose valacyclovir appears to be safe and effective for the prevention of cCMV among women with first-trimester primary CMV infection. New studies reveal high rates of vestibular dysfunction and neuropsychiatric manifestations among children with cCMV. Some studies report associations between pCMV and long-term consequences, including neurodevelopmental delay and bronchopulmonary dysplasia, among very low birth weight infants, in addition to high risk of sepsis and death acutely, which has motivated efforts to eliminate the virus from breast milk by different methods.
SUMMARY
More long-term complications of cCMV are increasingly recognized among children previously thought to be asymptomatic. Although a preventive CMV vaccine may be achievable, strategies to reduce the burden of cCMV disease include maternal education about risk-reduction behaviors, antiviral treatment of pregnant women with primary infection, and newborn screening to allow timely, appropriate care. Similarly, although it remains unclear if pCMV causes long-term problems, there is growing interest in identifying and preventing disease from CMV infections among preterm infants.
PubMed: 36465883
DOI: 10.1007/s40746-022-00261-y -
JPGN Reports Feb 2023Congenital cytomegalovirus (cCMV) is the most common congenital infection. Here, we report on a case of severe, refractory cCMV hepatitis resulting in end-stage liver...
Congenital cytomegalovirus (cCMV) is the most common congenital infection. Here, we report on a case of severe, refractory cCMV hepatitis resulting in end-stage liver disease. A male infant born at 37 weeks gestational age presented with petechiae, splenomegaly, and jaundice associated with a direct hyperbilirubinemia, elevated transaminases, and thrombocytopenia. Urine screen was positive for CMV, and he was treated with valganciclovir. He progressed to decompensated cirrhosis with ascites, hypoglycemia, and coagulopathy and was listed for liver transplant at 4 months of age. At 5 months of age, he developed massive hematemesis with hemorrhagic shock and underwent emergent portocaval shunt followed by living donor liver transplant with a left lateral segment graft. Postoperatively, he received CMV immune globulin and intravenous ganciclovir and cleared his viremia by 2 months post-transplant. This case illustrates the diagnostic and management challenges of severe cCMV hepatitis and reports a successful liver transplantation despite active CMV viremia.
PubMed: 38293317
DOI: 10.1097/PG9.0000000000000275 -
Nefrologia 2023We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus.
BACKGROUND
We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus.
METHODS
Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/μl, they received valganciclovir adjusted for their renal function.
RESULTS
132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation.
CONCLUSIONS
Due to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series.
PubMed: 36437203
DOI: 10.1016/j.nefroe.2022.11.018 -
Journal of Investigative Medicine High... 2022Chronic diarrhea is a common reason for consultation in renal transplant patients. infection is the cause of chronic diarrhea of infectious origin in 50% of cases, but...
Chronic diarrhea is a common reason for consultation in renal transplant patients. infection is the cause of chronic diarrhea of infectious origin in 50% of cases, but coinfection with tuberculosis is rare. We present the case of a renal transplant patient with chronic diarrhea, with a finding of left colon colitis and positive microbiological studies in biopsy for tuberculosis and . The patient received valganciclovir and anti-tubercular treatment with adequate evolution. Immunosuppressed patients may have diarrhea secondary to opportunistic infections; therefore, an algorithm for early diagnosis and treatment is recommended.
Topics: Humans; Mycobacterium tuberculosis; Cytomegalovirus; Kidney Transplantation; Opportunistic Infections; Cytomegalovirus Infections; Colitis; Diarrhea
PubMed: 36433691
DOI: 10.1177/23247096221139269 -
Journal of Immunology Research 2022Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells...
Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative.
Topics: Male; Humans; Young Adult; Adult; Cytomegalovirus; Cytomegalovirus Retinitis; Cord Blood Stem Cell Transplantation; T-Lymphocytes; Hematopoietic Stem Cell Transplantation
PubMed: 36426138
DOI: 10.1155/2022/6285510 -
BMC Infectious Diseases Nov 2022Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and...
BACKGROUND
Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients.
METHODS
The clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China.
RESULTS
A total of 308 patients were analyzed. The CMV serostatus was donor positive (D) recipient negative (R) in 19 (6.17%) patients, D/R in 233 (75.65%), D/R in 36 (11.69%), and D/R in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D/R serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05-6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92-9.42) were risk factors of CMV disease.
CONCLUSION
CMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.
Topics: Humans; Cytomegalovirus; Retrospective Studies; Seroepidemiologic Studies; Aftercare; Antiviral Agents; Patient Discharge; Valganciclovir; Cytomegalovirus Infections; Organ Transplantation
PubMed: 36418967
DOI: 10.1186/s12879-022-07853-x -
Bone Marrow Transplantation Feb 2023The management of cytomegalovirus (CMV) infection was assessed with a survey performed in 2020 by the Infectious Diseases Working Party of European Society for Blood and...
The management of cytomegalovirus (CMV) infection was assessed with a survey performed in 2020 by the Infectious Diseases Working Party of European Society for Blood and Marrow Transplantation (EBMT). One-hundred-eighty of the 579 EBMT centres (31%) responded. CMV monitoring with quantitative PCR for CMV-DNAemia was used by 97% of centres while the duration of monitoring was variable according to the patient immune recovery and the ongoing immunosuppressive therapy. CMV prophylaxis for high-risk patients was used in 101 (56%) of centres: letermovir in 62 centres (61%), aciclovir/valaciclovir in 19 centres (19%), ganciclovir/valganciclovir in 17 centres (17%), foscarnet in 3 (3%). The most used trigger for pre-emptive therapy was a threshold of >10 copies/ml or >10 IU/ml. Ganciclovir/valganciclovir confirmed the preferred first line treatment both for pre-emptive and CMV disease therapy. CMV-cytotoxic T-cells were used mainly in the setting of relapsing/refractory CMV disease. Forty-eight centres reported CMV refractory/resistant infection due to mutated CMV strain.This survey showed that letermovir prophylaxis is adopted by more than half of centres using a prophylaxis approach for CMV infection. How letermovir prophylaxis will modify other important pillars of daily CMV management, such as frequency of CMV-DNAemia monitoring and preemptive therapy, remain a matter of investigation.
Topics: Humans; Valganciclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Communicable Diseases
PubMed: 36396949
DOI: 10.1038/s41409-022-01863-8 -
Viruses Oct 2022Cytomegalovirus (CMV), a member of the Herpesviridae family, is frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients in absence... (Review)
Review
Cytomegalovirus (CMV), a member of the Herpesviridae family, is frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients in absence of antiviral prophylaxis, and is a major cause of morbidity and mortality in these vulnerable populations. Antivirals such ganciclovir, valganciclovir, and foscarnet are the backbone therapies, however drug toxicity and antiviral resistance may render these agents suboptimal in treatment. Newer therapies such as letermovir and maribavir have offered additional approaches for antiviral prophylaxis as well as treatment of drug resistant CMV infection, though may be limited by cost, drug intolerance, or toxicity. Adoptive immunotherapy, the transfer of viral specific T-cells (VSTs), offers a new approach in treatment of drug-resistant or refractory viral infections, with early clinical trials showing promise with respect to efficacy and safety. In this review, we will discuss some of the encouraging results and challenges of widespread adoption of VSTs in care of immunocompromised patients, with an emphasis on the clinical outcomes for treatment and prophylaxis of CMV infection among high-risk patient populations.
Topics: Humans; Immunotherapy, Adoptive; Hematopoietic Stem Cell Transplantation; Cytomegalovirus Infections; Ganciclovir; Cytomegalovirus; Antiviral Agents; Drug Resistance, Viral
PubMed: 36366468
DOI: 10.3390/v14112370