Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition) / 器官移植

Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

Antiviral therapy of adenovirus pneumonia / 中国小儿急救医学

Adenovirus pneumonia is a common type of pneumonia in immunocompetent and immunocompromised patients, and its prognosis is poor.Antiviral therapy includs ganciclovir, valganciclovir, cidofovir, brincidofovir, ribavirin and so on.Among them, cidofovir and brincidofovir have obvious antiviral activity against adenovirus in vitro and in vivo, but further RCT results are still needed.Therefore, antiviral therapy of adenovirus pneumonia still needs further study.

Antiviral therapy of adenovirus pneumonia / 中国小儿急救医学

Adenovirus pneumonia is a common type of pneumonia in immunocompetent and immu-nocompromised patients,and its prognosis is poor. Antiviral therapy includs ganciclovir,valganciclovir,cido-fovir,brincidofovir,ribavirin and so on. Among them,cidofovir and brincidofovir have obvious antiviral activ-ity against adenovirus in vitro and in vivo,but further RCT results are still needed. Therefore,antiviral therapy of adenovirus pneumonia still needs further study.

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies / A atividade in vitro de seis drogas antivirais contra o alfaherpesvírus equino tipo 1 indica que o ganciclovir é uma droga promissora para estudos in vivo

ABSTRACT: Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.

RESUMO: O alfaherpesvírus equino tipo 1 (EHV-1) está amplamente distribuído nos rebanhos equinos de todo o mundo e é um dos principais agentes causadores de abortos, doença respiratória e neurológica em equinos. Ainda não há tratamento específico para a infecção pelo EHV-1 em equinos, mas o potencial da terapia antiviral tem sido investigado. Neste trabalho, foi investigada a atividade anti-herpética in vitro dos fármacos Aciclovir, Ganciclovir, Foscanet, Famciclovir, Vidarabina e Cidofovir frente ao EHV-1. Para isso, foi realizado o teste de MTT, em que todas as drogas não apresentaram citotoxicidade até a dose de 200μg/mL. A seguir, diferentes concentrações dos fármacos foram submetidas ao teste de redução de placas virais em cultivo celular. O índice de seletividade (IS) dos compostos foi determinado usando a concentração citotóxica para 50% dos cultivos celulares (CC50), obtida pelo MTT, e pela concentração dos fármacos efetiva para inibir em 50% o número de placas virais (EC50). O Ganciclovir (IS: 490; EC50: 1,9μg/mL) foi o mais eficiente e seguro frente ao EHV-1, seguido pelo Cidofovir (IS: 150; EC50: 5,7 μg/mL), Aciclovir (IS: 37,4; EC50: 22,2μg/mL), Famciclovir (IS: 25,1; EC50: 24,5μg/mL), Vidarabina (IS: 12,2; EC50: 40,9μg/mL) e Foscarnet (IS: 6,9; EC50: 49,5μg/mL). Estes resultados indicam que o Ganciclovir constitui-se em um candidato para uso em experimentos in vivo.

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation

BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. RESULTS: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

A Case of Intralesional Cidofovir Injection for Recurrent Lacrimal Sac Squamous Papilloma

PURPOSE: To report a case of treating a patient with intralesional cidofovir injection who had frequently recurring lacrimal sac squamous papilloma after several excision surgeries. CASE SUMMARY: A 59-year-old man who had mass excision surgery at a different clinic nine months previously, visited our clinic to treat a recurring erythematous protruding mass near his left medial canthus that developed two months prior. Orbit CT showed a 15 x 25 mm-sized large mass located on the lacrimal sac adherent to medial orbital wall. An excision biopsy was performed and the histopathologic examination showed typical findings of squamous papilloma. Because the tumor recurred six months after the second surgery, we decided to perform adjuvant therapy using the antiviral agent cidofovir. The patient was treated with a 5 mg/mL intralesional cidofovir injection every three weeks. A transient recurrence presented on the upper lid at the third intralesional cidofovir injection site two months after the surgery, but the recurrent lesion improved after repeated injections. During the 12 months of follow-up, there were no complications and no evidence of recurrence. CONCLUSIONS: Intralesional cidofovir injections can be a safe and effective treatment for the management of recurrent squamous papilloma of the orbit, especially after total excision.

Intravesical Cidofovir in the Treatment of Hemorrhagic Cystitis after Unrelated Cord Blood Transplantation / 대한내과학회지

Hemorrhagic cystitis is a common complication in hematopoietic stem cell transplant recipients. We report a case of hemorrhagic cystitis after unrelated cord blood transplantation associated with adenovirus infection. Despite hydration, hematuria and large clots persisted. We instilled cidofovir into the bladder, which resulted in clearance of the adenovirus and significant clinical improvement. Our case emphasizes the effectiveness of intravesical cidofovir treatment for viral hemorrhagic cystitis.

Enfermedad por adenovirus en niños receptores de trasplante alogénico de células progenitoras hematopoyéticas / Adenovirus disease in children undergoing allogeneic hematopoietic stem cell transplantation

Introducción: Las infecciones virales son una causa conocida de morbi-mortalidad en pacientes receptores de trasplante alogénico de células progenitoras hematopoyéticas (TACPH). Los avances en la prevención y tratamiento de la infecciones por los virus del grupo Herpes obliga a centrar la atención en virus emergentes como el Adenovirus (Adv). Objetivos: Analizar la incidencia, evolución y factores de riesgo de la enfermedad por Adv en pacientes pediátricos trasplantados en un mismo centro. Métodos: Cohorte retrospectiva. Se analizaron los TACPH realizados entre abril/94 y abril/10. Se comparó la frecuencia de enfermedad por Adv antes y después del inicio del programa de TACPH con donantes no relacionados, en el año 2008. Resultados: n TCPH: 303. Incidencia enfermedad por Adv: 18p (5,4%), según período: 1994-2007: 2,8% vs 2008-2010: 18,9% (p<0,001). Pacientes con Adv: 61% varones, mediana edad: 8 años (r 0,6 - 18), días del trasplante: 55 (r 4- 295). La enfermedad por Adv tuvo una mortalidad del 22% y fue causa del 5,6% de la mortalidad relacionada con el trasplante. Los factores de riesgo para enfermedad por Adv fueron el antecedente de TACPH no relacionado (OR 6,6 IC95% 1,6-27,8) y la enfermedad por CMV (OR 12,3 IC95% 3,4- 44,5). Doce pacientes con viremia y/o enfermedad grave por Adv que recibieron tratamiento con Cidofovir (75%) tuvieron toxicidad renal moderada-severa y 33% de mortalidad por Adv. Conclusión: La enfermedad por Adv representa una causa importante de morbi-mortalidad en el TACPH. Los pacientes con factores de riesgo requieren estrategias de diagnóstico temprano y tratamiento oportuno (AU)

Introduction: Viral infections are a well-known cause of morbidity and mortality in patients who underwent allogeneic hematopoietic stem cell transplantation (AHSCT). Advances in the prevention and treatment of herpes virus infections have led to increased focus on other emerging viruses such as the adenovirus (ADV). Objectives: To analyze the incidence, evolution, and risk factors for ADV disease in pedia - tric patients who underwent AHSCT in a single center. Methods: All patients who underwent HSCT between April 1994 and April 2010 were retrospectively analyzed. Incidence rates of ADV disease before and after the introduction of the program of AHSCT from non-related donors in 2008 were compared. Results: HSCT n = 303. Incidence of ADV disease: 18p (5.4%), 1994-2007: 2.8% vs 2008-2010: 18.9% (p<0,001). Patients with ADV: 61% boys, mean age: 8 years (r 0.6 - 18), mean days after transplantation: 55 (r 4- 295). Mortality due to ADV disease was 22% and ADV was de cause of 5.6% of transplant-related mortality. Risk factors for disease due to ADV were AHSCT from a non-related donor (OR 6.6 CI 95% 1.6-27.8) and CMV disease (OR 12.3 CI 95% 3.4- 44.5). Twelve patients with viremia and/or severe disease due to ADV who received treatment with Cidofovir (75%) developed moderate- to-severe kidney toxicity and mortality due to ADV was 33%. Conclusion: ADV disease is an important cause of morbidity and mortality in AHSCT. At-risk Patients require early diagnostic strategies and adequate treatment (AU)

A Case of Intravesical Cidofovir Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Peripheral Blood Stem Cell Transplantation / 영남의대학술지

Hemorrhagic cystitis (HC) is a common complication after allogeneic transplantation. Early posttransplant HC occurs in association with cyclophosphamide, while later on HC results from viral infections such as polyomavirus BK (BKV) and adenovirus. We report here the case of a 57-year-old woman who received an instillation of cidofovir into the bladder for the treatment of hemorrhagic cystitis after allogeneic peripheral stem cell transplantation for her acute myeloid leukemia. Cyclophosphamide and busulfan were used as conditioning treatments. Cyclosporin was administered daily. On the 71st day after transplantation, the patient developed acute severe hemorrhagic cystitis, and BK virus was demonstrated in the urine samples using polymerase chain reaction. Her urinary symptoms did not improve in spite of palliative treatment, but a response was evident after intravesical cidofovir treatment.

Viruria in Adult Hemorrhagic Cystitis Patients Following Allogeneic Hematopoietic Stem Cell Transplantation and Implication of Antiviral Treatment

BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment. METHODS: Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC. RESULTS: Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence. CONCLUSION: Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.

Two cases of adenovirus pneumonia treated with cidofovir / 대한내과학회지

Adenovirus is one of the major viral cause of upper respiratory tract infection. Life-threatening adenovirus pneumonia is often reported in neonates, young children and immunocompromised hosts. It can rarely occur in previously healthy adults. Because there is no report on adenovirus pneumonia in adult patients in Korea, we report two cases of adenovirus pneumonia which developed in adult women. Despite of intravenous antibiotics therapy, the respiratory distress worsened and mechanical ventilation was applied. Microbiological tests for bacteria or fungi were negative. A high-resolution chest computed tomography showed bilateral patch ground-glass opacification. Subsequently, open lung biopsy specimen revealed diffuse alveolar damage and adenovirus was documented with immunohistochemical stain. Treatment with cidofovir led to prompt clinical improvement in our cases.

Quantitative Viral Load Monitoring and Cidofovir Therapy in BK Virus Nephropathy / 대한신장학회잡지

BACKGROUND: BK virus nephropathy (BKVN) has been increasingly recognized as an important cause of renal transplant dysfunction, but no specific antiviral therapy is currently available. Furthermore, a method evaluating the degree of viral infection has not been developed yet. Recently, there have been several case reports in which BKVN was successfully treated with cidofovir injection. In the current study, we report a case with BKVN successfully treated with cidofovir injection. In addition, we assessed the usefulness of quantitative viral load monitoring using a competitive polymerase chain reaction (PCR) in the treatment of BKVN. METHODS: A renal allograft recipient with BKVN was injected with cidofovir. To monitor BK viral load in urine and plasma, we developed a competitive PCR assay and followed the patient prospectively. RESULTS: A 49 year old renal transplant recipient developed a progressive rise in serum creatinine reaching 1.9 mg/dL at 15 months post-transplantation. Subsequently, the patient was diagnosed as BKVAN by allograft biopsy. At this time, BKV DNA was detected in plasma and urine. Despite a reduction of the dose of mycophenolate mofetil, serum creatinine continued to rise, which prompted the initiation of cidofovir trial. The patient was given intravenous cidofovir. After cidofovir treatment, BK virus associated findings disappeared on repeat biopsy, and BK virus in plasma was decreased to the undetectable level. For 7 months after cidofovir treatment, her renal function remained stable. CONCLUSION: Cidofovir therapy may be effective in the treatment for BKVN. Viral load in plasma reflected well the clinical and pathological course of the BK virus infection.