Adjunctive Use of Cidofovir and Intravenous Immunoglobulin to Treat Invasive Adenoviral Disease in Solid Organ Transplant Recipients

Permpalung, Nitipong; Mahoney, Monica V; Alonso, Carolyn D.

doi:10.1002/phar.2194

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…In our cohort, 21 patients were treated with cidofovir. Although data from large randomised controlled trials are lacking and standard therapy for adenovirus infections is not yet established, cidofovir has been shown to be an acceptable treatment for an adenovirus infection in patients with various conditions such as after solid organ transplants 24 and hematopoietic stem cell transplants 25 . However, data are scarce, yet positive, regarding cidofovir treatment in previously healthy people with severe illness 7,26,27 .…”

Section: Discussionmentioning

confidence: 99%

Adenovirus can be a serious, life‐threatening disease, even in previously healthy children

et al. 2021

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Aim Adenovirus infections are exceedingly common in childhood. However, little is known of the clinical characteristics of children admitted with severe infection to the paediatric intensive care unit (PICU). Methods Clinical data on children hospitalised with adenovirus infection between January 2005 and March 2020 were collected. We compared data between children hospitalised in the PICU and those who were not in a 1:2 ratio. Results During the study period, 69 children with adenovirus infection were admitted to the PICU, representing 5% of all hospitalised children with adenovirus. Thirty‐four (49%) were previously healthy children. Mortality occurred in 5 patients, and all had an underlying illness. Cidofovir was used in 21 children, including 11 who were previously healthy. No side effects were attributed to the treatment. During 2005–2014, viral co‐infection rates were 42% in the PICU group and 11% in the control group (p = 0.002). However, during 2015–2020, when the viral panel became widespread in our institution, the rates of co‐infection were similar in the two groups (32% and 34%, p = 1.0). Conclusion Our findings suggest that adenovirus may present as a serious, life‐threatening disease even in previously healthy children.

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Section: Discussionmentioning

confidence: 99%

Adenovirus can be a serious, life‐threatening disease, even in previously healthy children

et al. 2021

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“…To date, it has been reported that ribavirin and cidofovir treatment [ 41–44 ] and adoptive transfer of Ad-specific T cells [ 45, 46 ] effectively prevented Ad infections in patients following transplantation. Intravenous immunoglobulin (IVIG) has been used to treat severe Ad infection in combination with ribavirin and cidofovir [ 47–49 ], but the therapeutic effects of IVIG itself are unclear [ 50 ]. Our results suggest that the effect of IVIG is attenuated by progeny Ad in the presence of nAb and that inhibition of this infection is an attractive strategy for patients treated with IVIG.…”

Section: Discussionmentioning

confidence: 99%

The infectivity of progeny adenovirus in the presence of neutralizing antibody

Hirai

Sato

Koizumi

et al. 2021

Journal of General Virology

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Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.

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“…IVIG is being used in the treatment of other viral illnesses that affect the immunocompromised renal transplant population. In a small five patients study cidofovir in combination with IVIG was found to be helpful in clearing disease for patients with invasive adenovirus infection …”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta‐analysis

Bourassa‐Blanchette

Knoll

Hutton

et al. 2019

Clinical Transplantation

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Polyvalent immunoglobulin is commonly used for desensitization and treatment of antibody‐mediated rejection in kidney transplantation but its impact on other outcomes is not known. This systematic review investigated the impact of immunoglobulin prophylaxis on infection, rejection, graft loss, and death following kidney transplantation. A comprehensive literature search located 18 studies (n = 8 randomized controlled trials). None examined the effect of immunoglobulin prophylaxis in transplant recipients with hypogammaglobulinemia. Quality of included studies was variable with high to very high risk of bias. In the randomized trials, immunoglobulin use did not reduce cytomegalovirus infection (OR 0.68 [0.39, 1.21]; 6 studies, n = 295), rejection (OR 0.96 [0.50, 1.82]; 4 studies, n = 187), or graft loss (OR 1.03 [0.46, 2.30]; 6 studies, n = 265). In non‐randomized studies, immunoglobulin did not reduce cytomegalovirus infection (OR 0.63 [0.20, 1.94]; 6 studies, n = 361) or death (OR 1.32 [0.05, 38.79]; 3 studies, n = 222) but reduce rejection (OR 0.47 [0.24, 0.94]; 4 studies, n = 268) and graft loss (OR 0.15 [0.05, 0.43]; 2 studies, n = 118). Data were scarce and sample size of current evidence was small. Adequately powered randomized trials are needed to determine if immunoglobulin is an effective intervention to reduce infection, rejection, graft loss, or death following kidney transplantation with and without hypogammaglobulinemia.

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Adjunctive Use of Cidofovir and Intravenous Immunoglobulin to Treat Invasive Adenoviral Disease in Solid Organ Transplant Recipients

Cited by 13 publications

References 23 publications

Adenovirus can be a serious, life‐threatening disease, even in previously healthy children

Adenovirus can be a serious, life‐threatening disease, even in previously healthy children

The infectivity of progeny adenovirus in the presence of neutralizing antibody

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta‐analysis

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