Possible Persistence of West Nile Virus Infection

These Questions and Answers relate to a study published in the January 1, 2010 issue of the Journal of Infectious Diseases entitled "Persistent Infection with West Nile Virus Years after Initial Infection".¹

What did the study find?

The study found West Nile virus RNA in the urine of five of 25 patients tested. These patients had been diagnosed with West Nile virus encephalitis 1 to 6 years previously. The five who tested positive all had a history of high blood pressure. Some of the five patients complained of ongoing symptoms like feeling weak or tired, or having problems with their memory. It is not known if these symptoms were related to their West Nile virus infection. Attempts to grow the virus from urine of these five patients were not successful.

Can people have persistent infection with West Nile virus?

The findings of this study suggest that, in some people, West Nile virus may persist in the kidneys. There have been a few reports of persistent West Nile virus found in brain, spinal fluid, and blood of people who were immunocompromised. All people in the January 2010 article had West Nile virus encephalitis during their initial illness. It is not known how many people who have had West Nile virus encephalitis might have persistent West Nile virus in their urine. It is also not known if people who have had West Nile fever or asymptomatic West Nile virus infection can have similar findings.

In two subsequent U.S. studies that involved a total of 103 patients who had been diagnosed with WNV disease between a few weeks and 7 years previously, one person was found to have WNV RNA in their urine by transcription-mediated amplification (TMA) testing.^2,3 The positive urine had been collected 29 days after symptom onset from a woman aged 83 years who had had WNV encephalitis and was in a rehabilitation facility. The sample was obtained from a urine collection bag connected to an indwelling urine catheter. The patient died at 57 days after symptom onset, and additional urine samples could not be collected for further testing. These studies suggest that WNV RNA occurs infrequently in urine among persons following WNV infection.

Possible reasons for the discrepancy between the proportions of West Nile virus infected persons with detectable West Nile virus RNA in urine between the studies include: 

1. differences in test performance; 
2. differences in the study cohorts which may result in different incidence of WNV in urine; or 
3. that shedding of WNV RNA may be intermittent.

Can persistent West Nile virus RNA in the body cause medical problems like high blood pressure or kidney disease?

This is not known. In the study published in January 2010, all five patients who had West Nile virus RNA found in their urine were older men with high blood pressure. The high blood pressure was found prior to their initial West Nile virus disease, so it is unlikely that their blood pressure problems were caused by West Nile virus. One patient had developed kidney disease since his initial West Nile virus infection. It is not known if the kidney disease was related to West Nile virus or other medical problems.

In a subsequent study, the same group that published the January 2010 article reported a high prevalence of chronic kidney disease after long term follow-up in a cohort of participants previously infected with West Nile virus.⁴ The majority of those with kidney disease were in early stages of renal disease. However, people with pre-existing renal disease, diabetes, and hypertension are all at increased risk of neuroinvasive disease and serious illness following West Nile virus infection.⁵ It is difficult to sort out whether kidney disease may sometimes occur as a result of West Nile virus infection or whether some patients who have serious West Nile virus disease were already predisposed to develop chronic kidney disease unrelated to their infection. Additional studies are warranted to determine if persistence of West Nile virus may lead to kidney disease or other medical problems.

Can I have my patient’s urine tested for West Nile virus?

No. The test that was performed in the study was experimental and is not available for routine use. There are commercially available tests for West Nile virus RNA (i.e. WNV RT-PCR). However, the sensitivity and specificity of WNV RT-PCR on urine is unknown. In addition, the meaning of a positive test result in urine is unknown. For these reasons, it is not recommended that RT-PCR testing be performed on urine.

What is CDC doing to better understand the issue of persistent West Nile virus infection?

CDC is working with researchers to confirm that persistent West Nile virus infection occurs. If confirmed, CDC will look at how many people with West Nile virus disease develop persistent infection. The medical importance of persistent West Nile virus infection will also be studied. These studies will address if additional testing of certain groups should be done.

These questions and answers will be updated as more information becomes available.

References

1. Murray K, Walker C, Herrington E, et al. Persistent Infection with West Nile Virus Years after Initial Infection. J Infect Dis.  (2010) 201 (1): 2-4.

2. Gibney K, Lanciotti R, Sejvar J, et al. West Nile virus not detected in urine of 40 people tested 6 years after acute West Nile virus disease. J Infect Dis 2010; 203:344–7

3. Baty S, Gibney K, Staples J, et al. Evaluation for West Nile virus (WNV) RNA in urine of patients within 5 months of WNV infection. J Infect Dis  2012; 205:1476-7.

4. Nolan M, Podoll A, Hause A, et al. Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort. PLoS ONE  7(7): e40374.

5. Lindsey N, Staples J, Lehman J, Fischer M. Medical risk factors for severe West Nile virus disease, United States, 2008–2010. Am J Trop Med Hyg  2012; 87(1): 179–184.