Community-Acquired West Nile Virus Infection in Solid-Organ Transplant Recipients.

Community-Acquired West Nile Virus Infection in Solid-Organ Transplant Recipients. Transplantation 2004; 77: 399. D. Kumar, G. V. R. Prasad, J. Zaltzman, G. A. Levy, and A. Humar The sentinel chicken revisited: the impact of West Nile virus infection on transplant patients The infectious disease challenges for the 21st century continue to multiply. On the one hand, new pathogens are being identified and disseminated at a rapid pace—human immunodeficiency virus, the hemorrhagic fever viruses, severe acute respiratory syndrome, and multidrug-resistant bacteria (e.g., multidrug-resistant tuberculosis) serve as relatively recent examples. On the other hand, there has been an exponential increase in the number of immunocompromised individuals whose deficits in innate and acquired immunity allow normally trivial infections to cause complex and serious illness. These immunocompromised individuals are of four different types: those with congenital immunodeficiencies; those with severe deficiencies in the number or function of neutrophils (most commonly as a result of cancer chemotherapy); those with advanced human immunodeficiency virus infection; and, of greatest interest to this audience, those receiving exogenous immunosuppressive therapy to treat autoimmune disease or to manage rejection. In this issue of Transplantation, there are two reports (1,2) on the impact of West Nile virus (WNV) on transplant patients—a situation in which a relatively newly recognized pathogen in the Western Hemisphere and its impact on immunosuppressed patients is just being defined. The introduction of WNV to the Western Hemisphere in 1999 is a classic example of the impact of a newly introduced pathogen on a susceptible community (3–5). Given the prior absence of WNV in North America, we are witnessing the dissemination of this epidemic across the hemisphere. The presence of a completely naive avian population and competent vectors has led to rapid spread of this virus over the past 3 to 4 years, with an increasing impact on the human population because of the efficiency of transmission by means of the mosquito. As seen in the recent New York City epidemic, meningoencephalitis occurs in approximately 1 in 140 infections, with the rate substantially higher in older individuals (1 in 50 in those ≥65 vs. 1 in 300 in those <65 years old) (3). The neurologic manifestations have included the expected meningitis, encephalitis, and meningoencephalitis. In addition, not only has a polio-like acute flaccid paralysis been observed but other findings such as tremors, myoclonus, and Parkinson’s disease have been described (6). Nearly two decades ago, we designated transplant and other immunocompromised patients as “sentinel chickens,” serving as indicators of any excess trafficking of potential pathogens. Since then, we have learned a great deal more about these sentinels, whose impaired inflammatory response has a significant impact on all aspects of their care. As WNV spreads westward across North America, the impact of this outbreak on this special patient population is being defined (7). The report by Kumar et al. (2) in this issue of Transplantation suggests that the neurologic disease attack rate is increased 40-fold in single-organ transplant (SOT) patients compared with the general population. The ultimate morbidity and mortality also appears to be higher in SOT patients, with three of six patients reported (1,2) dying or having residual paresis compared with a 4% to 14% rate in the general population. This is in keeping with the observations made in other viral infections such as influenza, parainfluenza III, and enterovirus, where the consequences of infection are far greater in the transplant population. The diagnosis of this infection can be problematic, typically relying on the development of antibodies to the virus, with the demonstration of a fourfold or greater titer increase or primary seroconversion being the endpoint that is sought. In normal hosts, this occurs early in the clinical illness (90% within 8 days), whereas in immunosuppressed individuals, seroconversion may be substantially delayed by weeks or months or completely extinguished. This is not a surprising consequence of immunosuppression. For example, a recent report from Ontario demonstrated that three of seven immunosuppressed patients had substantially delayed antibody response by 1 to 2 months (7). How then should the diagnosis of WNV be made in a seronegative transplant patient? The future in diagnostic testing in this patient group must use direct viral nucleic acid detection. Although polymerase chain reaction of the blood for WNV has been found to be relatively insensitive in some studies, this should be less of a concern in SOT patients, as the pathogen burden in this population is typically high. In addition, radiologic assessment may facilitate the diagnosis, as Desalvo and colleagues (1) note that significant magnetic resonance imaging abnormalities were noted in both cases they report; thalamic and midbrain lesions have also been noted by others (6). Given similar findings reported with central nervous system disease caused by eastern equine encephalitis, these findings may emerge as an important diagnostic clue in central nervous system disease caused by arboviruses (6,8). Patients undergoing organ transplantation are at risk for contracting WNV and other pathogens not only from the donor or the procedure itself, through blood products (9), but also through community acquisition. Every effort must be made to diminish transmission through all of these routes, through enhanced screening procedures in blood and tissue banks and thorough advice to SOT patients to minimize exposure to potential vectors along with enhanced community-based preventive measures, such as mosquito control programs. It is a tragedy to navigate successfully all the hurdles transplantation requires—pretransplant organ insufficiency, technically complex surgery, rejection, and fluctuating levels of immunosuppression—only to have the patient die as a result of a preventable community infection. There is no established therapy for WNV infection, with therapeutic interventions such as interferon, ribavirin, and intravenous immunoglobulin (WNV antibody-enhanced lots) (10) being used with anecdotal success at best. Thus, vigilance to minimize exposure to common community pathogens is paramount. Although the data from transplant patients with WNV infection are still fragmentary, it is already clear that the attack rate for clinical disease is high; the gravity of the illness is greater; reflecting this last, the mortality rate appears to be higher; and the serologic approach to diagnosis is less reliable. What, then, have we learned about this illness and other illnesses developing in this patient population? Presentation will be more occult. Typically, unlike the steady clinical decline observed in the general patient, the transplant patient remains relatively well until he or she “falls off the cliff.” At this point, the organism burden is greater, the extent of disease is greater, the prognosis is poorer, and, if this is an organism that can be spread, the transmissibility is increased. Community-dwelling immunosuppressed patients are analogous to the proverbial sentinel chicken, allowing identification of a probable community outbreak of disease earlier than might otherwise occur. Therefore, active surveillance for such infections in transplant patients is warranted to optimize not only their care but also the care of the larger community, as identification of the presence of a new community pathogen will allow the public health authorities to mobilize control measures more efficiently.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.