Case presentation: persistent adenovirus B3 infections associated with bronchiolitis obliterans treated with cidofovir in a child with mosaic tetrasomy 9p

Abstract

BackgroundAdenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child’s long-term clinical outcomes.Case presentationWe present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation.ConclusionsAdenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation.

Evaluation of Risk Factors for Exacerbations in Children with Adenoviral Pneumonia

“…Unfortunately, 14%-16% of the recovered patients may have sequelae of different degrees [24]; occlusive bronchitis and bronchiectasis are the most common complications in children with severe adenoviral pneumonia. Some severe adenoviral pneumonia cases may still hear wheezing in the lungs during recovery, accompanied by varying degrees of wheezing [25]. Therefore, treatment to improve small airway ventilation is still needed in the adenoviral pneumonia recovery period to improve the long-term prognosis of children as much as possible.…”

Successful Treatment of Severe Adenoviral ARDS Using Cidofovir in a Case with Cerebral Palsy

“…Adenovirüs zarfsız, çift sarmallı, multipl serotipli bir DNA virüsüdür. 4 Adenovirüs tipik olarak hafif ve kendi kendini Adenovirüse Bağlı Ağır ARDS'nin Sidofovirle Tedavisi Gün ve ark. Şekil 1.…”

“…Sidofovir damar içi olarak verilir ve öncesinde ve sonrasında probenesid verilerek nefrotoksik etkisi azaltılır. 4 Sidofovir damar içi verildiğinde ilacın %90'ınından fazlası tübüler sekresyon ve filtrasyon yoluyla 24 saatte idrarda değişmeden atılır. Bu hızlı eliminasyona rağmen sidofovirin hücre içi antiviral etkisi uzun süre devam eder.…”

Human adenovirus infection of 53 children in Jilin Province of China: the clinical and bronchoscopic features

“…In our study, this method could make no significant difference between the febrile time of children in the severe pneumonia group and non-severe pneumonia group. As an antiviral drug, cidofovir has been reported as a treatment for HAdV infection in the United Kingdom, the United States and South Korea [38][39][40], but it has not been reported in China.…”