Melissa S. Nolan

Prevalence of Chronic Kidney Disease and Progression of Disease Over Time among Patients Enrolled in the Houston West Nile Virus Cohort

Introduction In experimental models of West Nile virus (WNV) infection, animals develop chronic kidney infection with histopathological changes in the kidney up to 8-months post-infection. However, the long term pathologic effects of acute infection in humans are largely unknown. The purpose of this study was to assess renal outcomes following WNV infection, specifically the development of chronic kidney disease (CKD). Methods In a cohort of 139 study participants with a previous diagnosis of WNV infection, we investigated the prevalence of CKD using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria based on the Modification of Diet in Renal Disease (MDRD) formula and urinary abnormalities, and assessed various risk factors and biomarkers. Results Study participants were primarily male (60%) and non-Hispanic white (86%) with a mean age of 57 years. Most (83%) were four to nine years post-infection at the time of this study. Based on the KDOQI definition, 40% of participants had evidence of CKD, with 10% having Stage III or greater and 30% having Stage I–II. By urinary dipstick testing, 26% of patients had proteinuria and 23% had hematuria. Plasma NGAL levels were elevated in 14% of participants while MCP-1 levels were increased in 12%. Over 1.5 years, the average change in eGFR was −3.71 mL/min/1.73 m2. Only a history of Neuroinvasive WNV disease was independently associated with CKD following multivariate analysis. Discussion We found a high prevalence of CKD after long term follow-up in a cohort of participants previously infected with WNV. The majority of those with CKD are in Stage I-II indicating early stages of renal disease. Traditional risk factors were not associated with the presence of CKD in this population. Therefore, clinicians should regularly evaluate all patients with a history of WNV for evidence of CKD.

West Nile virus infection among humans, Texas, USA, 2002-2011.

We conducted an epidemiologic analysis to document West Nile virus infections among humans in Texas, USA, during 2002–2011. West Nile virus has become endemic to Texas; the number of reported cases increased every 3 years. Risk for infection was greatest in rural northwestern Texas, where Culex tarsalis mosquitoes are the predominant mosquito species.

West Nile virus, Texas, USA, 2012.

During the 2012 West Nile virus outbreak in Texas, USA, 1,868 cases were reported. Male patients, persons >65 years of age, and minorities were at highest risk for neuroinvasive disease. Fifty-three percent of counties reported a case; 48% of case-patients resided in 4 counties around Dallas/Fort Worth. The economic cost was >

Findings of Long-Term Depression up to 8 Years Post Infection From West Nile Virus

47.6 million.

Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus

OBJECTIVE To examine the psychological sequelae following West Nile virus (WNV) infection among a large cohort of participants over an 8-year period. DESIGN We conducted a longitudinal study to assess mental health outcomes among a cohort of 171 WNV-positive participants in Houston, Texas. RESULTS We found 35% of participants met the Center for Epidemiologic Studies Depression scale definition for new onset clinical depression. Multivariate analysis found that severe depression was significantly associated with gender and physical disability (Barthel index score <100) at 5 years post-WNV infection. CONCLUSIONS Practitioners should be aware of depression as a possible outcome in patients who were infected with WNV and include this as a part of their routine assessment.

Proximity of Residence to Bodies of Water and Risk for West Nile Virus Infection: A Case-Control Study in Houston, Texas

Infections with West Nile virus (WNV) are typically asymptomatic, but some patients experience severe neurological disease and even death. Over 1500 fatalities have resulted from the more than 37,000 WNV cases in the USA between 1999 and 2012. While it is clear that age is a significant risk factor, markers of immune status associated with susceptibility to severe infections are incompletely defined. We have taken advantage of stable characteristics of individual status to profile immune markers from a stratified cohort of healthy subjects with a history of asymptomatic or severe infection with WNV. We characterized individual variations in antibody and serum cytokine levels and genome-wide transcriptional profiles of peripheral blood cells (PBMCs). While antibody levels were not significantly different between cohorts, we found that subjects with a history of severe infection had significantly lower levels of serum IL-4, and that these changes in IL-4 levels were associated with altered gene expression patterns in PBMCs. In addition, we identified a signature of 105 genes that displayed altered expression levels when comparing subjects with a history of asymptomatic or severe infection. These results suggest that systems-level analysis of immune system status can be used to identify factors relevant for susceptibility to severe infections, and specifically point to an important contribution for IL-4 in resistance to WNV infection.

The state of the antivaccine movement in the United States: A focused examination of nonmedical exemptions in states and counties

West Nile virus (WNV), a mosquito-borne virus, has clinically affected hundreds of residents in the Houston metropolitan area since its introduction in 2002. This study aimed to determine if living within close proximity to a water source increases ones odds of infection with WNV. We identified 356 eligible WNV-positive cases and 356 controls using a population proportionate to size model with US Census Bureau data. We found that living near slow moving water sources was statistically associated with increased odds for human infection, while living near moderate moving water systems was associated with decreased odds for human infection. Living near bayous lined with vegetation as opposed to concrete also showed increased risk of infection. The habitats of slow moving and vegetation lined water sources appear to favor the mosquito-human transmission cycle. These methods can be used by resource-limited health entities to identify high-risk areas for arboviral disease surveillance and efficient mosquito management initiatives.

Clinical Evidence of Acute Mesoamerican Nephropathy.

In a Policy Forum, Peter Hotez and colleagues discuss vaccination exemptions in US states and possible consequences for infectious disease outbreaks.

Long‐term neuromuscular outcomes of west nile virus infection: A clinical and electromyographic evaluation of patients with a history of infection

Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

Newly Recognized Pediatric Cases of Typhus Group Rickettsiosis, Houston, Texas, USA

Introduction: Neuromuscular clinical manifestations during acute West Nile virus (WNV) infection are well documented; however, long‐term neurologic outcomes still require investigation. Methods: We conducted a long‐term follow‐up study in patients with history of WNV infection. Of the 117 patients who participated in neurologic and neurocognitive evaluations, 30 were referred for neuromuscular and electrodiagnostic evaluation based on abnormal findings. Results: We found that 33% of these patients (10 of 30) showed abnormalities on nerve conduction and/or needle electromyography due to primary or secondary outcomes of WNV infection. Most common electrodiagnostic findings and causes of long‐term disability were related to anterior horn cell poliomyelitis (WNV poliomyelitis). Electrical data on these patient populations were similar to those observed in chronic poliomyelitis. Discussion: With more than 16,000 cases of WNV neuroinvasive disease reported across the USA since 1999, understanding clinical outcomes from infection will provide a resource for physicians managing long‐term care of these patients. Muscle Nerve 57: 77–82, 2018