Epidemiological and Genetic Characteristics of Rabies Virus Transmitted Through Organ Transplantation

Abstract

In January 2016, two patients died of rabies after receiving kidney transplants from a common organ donor at a hospital in Changsha, Hunan, China. The medical records, epidemiological data of the organ donor, two kidney and a liver recipients were reviewed. Intravitam saliva samples of the two kidney recipients were tested for rabies virus (RABV) using real-time RT-PCR, and the nucleoprotein (N) gene was amplified and sequenced by Sanger sequencing. Whole genome sequences were analyzed using next-generation sequencing. The N genes of the two kidney recipients showed 100% nucleic acid identity. Phylogenetic analysis of the complete genome, N and glycoprotein (G) genes indicated that the RABV was homologous with dog isolates from the Hunan province and belong to the China I lineage, which is widespread in China. The organ donor was a 22-month-old boy who died from unknown acute progressive encephalitis. After undergoing sub-hypothermia hibernation therapy, rabies-associated symptoms were atypical, and rabies was neglected because serum RABV-specific antibodies were negative. An unknown wound on the forehead of the donor was found 2 months before the onset of symptoms. Based on the clinical, epidemiological, and molecular findings, we speculated that the RABV initially originated in the donor from a dog bite, and was then transmitted to the recipients by organ transplantation. An uncertain exposure history and misdiagnosis played important roles in the spread of the RABV. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially in potential organ donors.

Rabies: a medical perspective

“…Soon after, transmission occurred to another three organ recipients in Germany (7). Subsequently, in the USA, organ transplantation in Maryland (donor from North Carolina) resulted in a single case (8); in Kuwait, it resulted in four cases (9,10); and there have been seven additional cases in the People' s Republic of China from three donors (11,12,13,14). In all rabies cases transmitted by tissue or organ transplantation, infectious RABV is thought to be present in transplanted nerves through which it gains access to nerves of the host.…”

High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance

“…The rabies virus (RABV) causes an acute, deadly brain infection in humans and other species. It is transmitted through a bite or scratch from a rabid animal's saliva [60] . Researchers were able to compare the deep genetic diversity and evolution of RABV subpopulations, microevolution, and adaptability patterns success can be attributed to the Illumina MiSeq platform [61] .…”

Susceptibility of solid organ transplant recipients to viral pathogens with zoonotic potential: A mini-review

“…The virus is present in wild and domestic animal reservoirs, and is the etiological agent of a fatal disease, causing 60,000 deaths worldwide every year. 53 Its transmission most often occurs through the bite of an infected mammal. In 1979, the first report of donor transmission of rabies was through corneal transplantation.…”

“…New-generation sequencing was carried out to obtain the complete genome of the viruses found in the recipients, and phylogenetic analysis indicated great similarity with the RABV lineage circulating in dogs in China. 53 …”