Reemergence of Dengue in Southern Texas, 2013.

During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico.

Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-April 14, 2016.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes, and symptoms of infection can include rash, fever, arthralgia, and conjunctivitis (1).* Zika virus infection during pregnancy is a cause of microcephaly and other severe brain defects (2). Infection has also been associated with Guillain-Barré syndrome (3). In December 2015, Puerto Rico became the first U.S. jurisdiction to report local transmission of Zika virus, with the index patient reporting symptom onset on November 23, 2015 (4). This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico. During November 1, 2015-April 14, 2016, a total of 6,157 specimens from suspected Zika virus-infected patients were evaluated by the Puerto Rico Department of Health (PRDH) and CDC Dengue Branch (which is located in San Juan, Puerto Rico), and 683 (11%) had laboratory evidence of current or recent Zika virus infection by one or more tests: reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA). Zika virus-infected patients resided in 50 (64%) of 78 municipalities in Puerto Rico. Median age was 34 years (range = 35 days-89 years). The most frequently reported signs and symptoms were rash (74%), myalgia (68%), headache (63%), fever (63%), and arthralgia (63%). There were 65 (10%) symptomatic pregnant women who tested positive by RT-PCR or IgM ELISA. A total of 17 (2%) patients required hospitalization, including 5 (1%) patients with suspected Guillain-Barré syndrome. One (<1%) patient died after developing severe thrombocytopenia. The public health response to the outbreak has included increased laboratory capacity to test for Zika virus infection (including blood donor screening), implementation of enhanced surveillance systems, and prevention activities focused on pregnant women. Vector control activities include indoor and outdoor residual spraying and reduction of mosquito breeding environments focused around pregnant women's homes. Residents of and travelers to Puerto Rico should continue to employ mosquito bite avoidance behaviors, take precautions to reduce the risk for sexual transmission (5), and seek medical care for any acute illness with rash or fever.

Characterization of Puerto Rican West Nile Virus isolates in mice.

BACKGROUND: West Nile virus (WNV) is a neurotropic arbovirus that was first isolated in 1937 in the West Nile District of Uganda. The virus emerged in New York in 1999 and is now endemic in North America (2007). The first virus isolates from Puerto Rico were obtained in 2007 from a chicken (PR20wh) and a mosquito pool (PR423). Our study further characterized these viral isolates using in vitro plaque morphology assays and in vivo using a Balb/c mice pathogenesis model. METHODS AND RESULTS: In the in vitro experiments, PR WNV isolates produced significantly smaller plaques in Vero cells compared to the New York 1999 strain (NY99). For the in vivo experiments, PR WNV isolates were propagated in mammalian (Vero) and insect (C6/36) cell lines and then inoculated in Balb/c mice. When WNV was propagated in Vero cells, we observed a trend towards significance in the survival rate with PR20wh compared to NY99 (log rank, p = 0.092). Regardless of whether the viral isolates were propagated in Vero or C6/36 cells, we found a significantly greater survival in mice infected with PR20wh strain, when compared to NY99 (log rank, p = 0.04), while no statistical difference was detected between PR423 and NY99 (p = 0.84). The average survival time (AST) in mice was significantly lower in C6/36-derived PR423 when compared to C6/36-derived NY99 (t-test, p = 0.013), and Vero-derived PR423 (t-test, p < 0.001). Eight days post infection in mice the viral load in brain tissue for Vero-derived PR423 was significantly higher when compared to NY99 and PR20wh. CONCLUSIONS: These results suggest that the PR WNV isolate, PR20wh, is a less pathogenic strain in mice than NY99. Moreover, we found that PR423 is a pathogenic isolate that causes faster mortality than NY99, when propagated in C6/36.

The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Rico.

BACKGROUND: Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study. METHODS: Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity. RESULTS: Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course. CONCLUSION: While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.

Use of Household Cluster Investigations to Identify Factors Associated with Chikungunya Virus Infection and Frequency of Case Reporting in Puerto Rico.

BACKGROUND: Chikungunya virus (CHIKV) is transmitted by Aedes species mosquitoes and is the cause of an acute febrile illness characterized by potentially debilitating arthralgia. After emerging in the Caribbean in late 2013, the first locally-acquired case reported to public health authorities in Puerto Rico occurred in May 2014. During June-August 2014, household-based cluster investigations were conducted to identify factors associated with infection, development of disease, and case reporting. METHODOLOGY/PRINCIPAL FINDINGS: Residents of households within a 50-meter radius of the residence of laboratory-positive chikungunya cases that had been reported to Puerto Rico Department of Health (PRDH) were offered participation in the investigation. Participants provided a serum specimen and answered a questionnaire that collected information on demographic factors, household characteristics, recent illnesses, healthcare seeking behaviors, and clinical diagnoses. Current CHIKV infection was identified by rRT-PCR, and recent CHIKV infection was defined by detection of either anti-CHIKV IgM or IgG antibody. Among 250 participants, 74 (30%) had evidence of CHIKV infection, including 12 (5%) with current and 62 (25%) with recent CHIKV infection. All specimens from patients with CHIKV infection that were collected within four days, two weeks, and three weeks of illness onset were positive by RT-PCR, IgM ELISA, and IgG ELISA, respectively. Reporting an acute illness in the prior three months was strongly associated with CHIKV infection (adjusted odds ratio [aOR] = 21.6, 95% confidence interval [CI]: 9.24-50.3). Use of air conditioning (aOR = 0.50, 95% CI = 0.3-0.9) and citronella candles (aOR = 0.4, 95% CI = 0.1-0.9) were associated with protection from CHIKV infection. Multivariable analysis indicated that arthralgia (aOR = 51.8, 95% CI = 3.8-700.8) and skin rash (aOR = 14.2, 95% CI = 2.4-84.7) were strongly associated with CHIKV infection. Hierarchical cluster analysis of signs and symptoms reported by CHIKV-infected participants demonstrated that fever, arthralgia, myalgia, headache, and chills tended to occur simultaneously. Rate of symptomatic CHIKV infection (defined by arthralgia with fever or skin rash) was 62.5%. Excluding index case-patients, 22 (63%) participants with symptomatic CHIKV infection sought medical care, of which 5 (23%) were diagnosed with chikungunya and 2 (9%) were reported to PRDH. CONCLUSIONS/SIGNIFICANCE: This investigation revealed high rates of CHIKV infection among household members and neighbors of chikungunya patients, and that behavioral interventions such as use of air conditioning were associated with prevention of CHIKV infection. Nearly two-thirds of patients with symptomatic CHIKV infection sought medical care, of which less than one-quarter were reportedly diagnosed with chikungunya and one-in-ten were reported to public health authorities. These findings emphasize the need for point-of-care rapid diagnostic tests to optimize identification and reporting of chikungunya patients.