Typically, rabies is fatal once clinical signs develop. Although persistent infections occur regularly for other virus infections, they have not been documented unquestionably in rabies, mainly because of the added complexity of the disease’s relatively long incubation period. The carrier or asymptomatic rabies state was once considered to be important for public health, despite lack of adequate evidence that the phenomenon actually exists. This concern has been raised repeatedly from the early 1930s until recently (7
). Reported carrier hosts have included vampire bats (8,9
), cats (10
), dogs (11–15
), and hyenas (7
). Because rabid dog bites are responsible for ≈99% of all human rabies cases in the world (16
), the possibility of a carrier state or asymptomatic form of canine rabies deserves serious evaluation. Unfortunately, this possibility remains highly speculative. Although some investigators have questioned reports of a carrier state in dogs (17
), an author reported RABV isolation from brains of healthy dogs (6
). Carrier dog RABV isolates were even characterized at the molecular level in 1996 (15
Similarly, reports of healthy-dog carriers were consecutively published in China in 1982 (18
), 1999 (19
), 2006 (20
), and 2007 (21
). Tang found that 5 (1.76%) of 283 healthy-looking dogs in Guangxi province were positive for RABV by reverse transcription–PCR (RT-PCR) and virus isolation (5
). Another study showed that 24 of 42 RABV isolates were taken from dogs or cats classified as clinically normal (3
). All animals from these studies were from areas experiencing rabies epidemics.
All cumulative convincing data for more than half a century from various parts of the world call into question either the concept of a rabies carrier state or the quality of research indicating such a state. Other persistent virus infections routinely occur in lymphocytes, monocytes, macrophages, and dendritic cells through the viruses’ curtailment of the host’s antivirus immune responses. Experimental RABV replication in murine bone marrow macrophages and in human macrophage–like cell lines suggests a mechanism of virus persistence (22
). However, wild-type RABV is highly neurotropic. If RABV persistent infection occurs in neurons, these findings contradict the current understanding of RABV pathogenesis. Clearly, RABV infection causes minor morphologic changes in neurons but may result in neurophysiologic dysfunction. Also, virus persistence generally is life-long in infected hosts. The longest surviving presumed carrier dog lived for only 16 months; in this dog, the tonsil was found to be the only organ from which the virus was isolated (14
). No data are available concerning how long such carrier dogs survive. In healthy vampire bats, the duration of salivary excretion of RABV was reported to be 690 days after infection by an extremely high dose of RABV (8
). Generally, persistent infections are characterized by an excess of viruses or virus antigens; free antibodies, which circulate without binding to antigens, are difficult to detect. However, experimental carrier dogs and vampire bats presented high rates of virus-neutralizing antibodies in serum in these reports (8,14
). From an evolutionary perspective, a carrier dog with normal behavior does not pose an advantage for virus survival because biting when an animal is controlled by an aggressive brain is the only major route for RABV to spread. Animal behavior change is fundamental for RABV survival/transmission. Therefore, if carrier dogs exist, they are inferior to rabid dogs for disease transmission.
In a report by Zhang (17
), 15 dogs that were diagnosed as positive by ELISA were confirmed to be negative by the standard direct fluorescent antibody (DFA) method. Explanations for these contradictory findings include misidentification of infected dogs, detection of RABV early in the prodromal course once it has reached the central nervous system after infection and incubation, and inadequate diagnostics. These phenomena, rather than the existence of carrier hosts, may explain historical reports of asymptomatic rabies in enzootic areas.