Kristy O. Murray

Persistent Infection with West Nile Virus Years after Initial Infection

West Nile virus (WNV) RNA was demonstrated in 5 (20%) of 25 urine samples collected from convalescent patients 573-2452 days (1.6-6.7 years) after WNV infection. Four of the 5 amplicons sequenced showed >99% homology to the WNV NY99 strain. These findings show that individuals with chronic symptoms after WNV infection may have persistent renal infection over several years.

West Nile virus and its emergence in the United States of America.

Zoonotic West Nile virus (WNV) circulates in natural transmission cycles involving certain mosquitoes and birds, horses, humans, and a range of other vertebrates are incidental hosts. Clinical infections in humans can range in severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its introduction to the Western Hemisphere in 1999, WNV had spread across North America, Central and South America and the Caribbean, although the vast majority of severe human cases have occurred in the United States of America (USA) and Canada. By 2002–2003, the WNV outbreaks have involved thousands of patients causing severe neurologic disease (meningoencephalitis and poliomyelitis-like syndrome) and hundreds of associated fatalities in USA. The purpose of this review is to present recent information on the epidemiology and pathogenicity of WNV since its emergence in North America.

Worldwide patterns of genetic differentiation imply multiple ‘domestications’ of Aedes aegypti, a major vector of human diseases

Understanding the processes by which species colonize and adapt to human habitats is particularly important in the case of disease-vectoring arthropods. The mosquito species Aedes aegypti, a major vector of dengue and yellow fever viruses, probably originated as a wild, zoophilic species in sub-Saharan Africa, where some populations still breed in tree holes in forested habitats. Many populations of the species, however, have evolved to thrive in human habitats and to bite humans. This includes some populations within Africa as well as almost all those outside Africa. It is not clear whether all domestic populations are genetically related and represent a single ‘domestication’ event, or whether association with human habitats has developed multiple times independently within the species. To test the hypotheses above, we screened 24 worldwide population samples of Ae. aegypti at 12 polymorphic microsatellite loci. We identified two distinct genetic clusters: one included all domestic populations outside of Africa and the other included both domestic and forest populations within Africa. This suggests that human association in Africa occurred independently from that in domestic populations across the rest of the world. Additionally, measures of genetic diversity support Ae. aegypti in Africa as the ancestral form of the species. Individuals from domestic populations outside Africa can reliably be assigned back to their population of origin, which will help determine the origins of new introductions of Ae. aegypti.

Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood

Infection with Zika virus is an emerging public health crisis. We observed prolonged detection of virus RNA in vaginal mucosal swab specimens and whole blood for a US traveler with acute Zika virus infection who had visited Honduras. These findings advance understanding of Zika virus infection and provide data for additional testing strategies.

Host Genetic Risk Factors for West Nile Virus Infection and Disease Progression

West Nile virus (WNV), a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035) and MX1, (OR 0.19, p = 0.014) were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003) was associated with increased risk for West Nile encephalitis and paralysis (WNE/P). Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

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.

Approaches to refining estimates of global burden and economics of dengue.

Dengue presents a formidable and growing global economic and disease burden, with around half the worlds population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and hosts immune status, age, pre-existing medical conditions, all contribute to the diseases complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools for diagnosis, vaccination, vector control, and treatment are being developed, these recommended steps should improve objective, systematic measures of dengue burden to strengthen health policy decisions.

Case Report: Evidence of Autochthonous Chagas Disease in Southeastern Texas

Autochthonous transmission of Trypanosoma cruzi in the United States is rarely reported. Here, we describe five newly identified patients with autochthonously acquired infections from a small pilot study of positive blood donors in southeast Texas. Case-patients 1-4 were possibly infected near their residences, which were all in the same region ∼100 miles west of Houston. Case-patient 5 was a young male with considerable exposure from routine outdoor and camping activities associated with a youth civic organization. Only one of the five autochthonous case-patients received anti-parasitic treatment. Our findings suggest an unrecognized risk of human vector-borne transmission in southeast Texas. Education of physicians and public health officials is crucial for identifying the true disease burden and source of infection in Texas.

Depression after Infection with West Nile Virus1

Previous reports have noted depression after West Nile virus (WNV) infection. We further measured this outcome and found that 31% of patients reported new-onset depression and 75% of these had Center for Epidemiologic Studies Depression scores indicative of mild-to-severe depression. Physicians should be aware of neuropsychiatric consequences of WNV in patients.

Identification of Dengue Fever Cases in Houston, Texas, with Evidence of Autochthonous Transmission Between 2003 and 2005

Houston, Texas, maintains an environment conducive to dengue virus (DENV) emergence; however, surveillance is passive and diagnostic testing is not readily available. To determine if DENV is present in the area, we tested 3768 clinical specimens (2138 cerebrospinal fluid [CSF] and 1630 serum) collected from patients with suspected mosquito-borne viral disease between 2003 and 2005. We identified 47 immunoglobulin M (IgM)-positive dengue cases, including two cases that were positive for viral RNA in serum for dengue serotype 2. The majority of cases did not report any history of travel outside the Houston area prior to symptom onset. The epidemic curve suggests an outbreak occurred in 2003 with continued low-level transmission in 2004 and 2005. Chart abstractions were completed for 42 of the 47 cases; 57% were diagnosed with meningitis and/or encephalitis, and 43% met the case definition for dengue fever. Two of the 47 cases were fatal, including one with illness compatible with dengue shock syndrome. Our results support local transmission of DENV during the study period. These findings heighten the need for dengue surveillance in the southern United States.