Successful treatment of disseminated adenovirus infection with cidofovir and intravenous immunoglobulin in an infant following heart transplant

Serrano, Ryan; Darragh, Robert K.; Parent, John J.

doi:10.1017/s1047951118000379

Cited by 6 publications

(5 citation statements)

References 4 publications

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“…The incidence of AdV infections among SOT recipients is 5 to 22%, usually within the first 6 months posttransplantation. 4 8 79 145 200 201 202 Adenovirus infections have been noted in recipients of intestinal, 203 204 liver, 205 206 207 208 kidney, 119 123 128 209 210 211 heart, 200 212 213 214 and lung 215 216 transplants. Among SOT recipients, risk factors for AdV include pediatric age, 4 79 208 217 donor-positive/recipient-negative AdV status, 79 and receipt of antilymphocyte antibodies.…”

Section: Specific Patient Populations At Riskmentioning

confidence: 99%

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

Lynch

Kajon

2021

Semin Respir Crit Care Med

129

187

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Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.

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Section: Specific Patient Populations At Riskmentioning

confidence: 99%

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

Lynch

Kajon

2021

Semin Respir Crit Care Med

129

187

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“…To date, it has been reported that ribavirin and cidofovir treatment [41][42][43][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][48][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: 84%

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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“…Specific T cell response correlates with viral clearance [ 1 ]. Infusion of intravenous immunoglobulin is routinely recommended in immunocompromised patients, considering the potential of containing high levels of neutralising antibodies against lower adenoviral serotypes [ 24 ], commonly co-administered with other therapeutic approaches [ 25 ]. Tapering immunosuppression is desirable, but is not always an option.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir

Grasa

Vilavedra²,

Pérez-Arenas

et al. 2023

Microorganisms

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Background: human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. Methods: Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. Results: 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. Conclusions: hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

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Successful treatment of disseminated adenovirus infection with cidofovir and intravenous immunoglobulin in an infant following heart transplant

Cited by 6 publications

References 4 publications

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

The infectivity of progeny adenovirus in the presence of neutralizing antibody

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir

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