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Kate Russell - Top 30 Publications

Male-to-Female Sexual Transmission of Zika Virus-United States, January-April 2016.

We report on 9 cases of male-to-female sexual transmission of Zika virus in the United States occurring January-April 2016. This report summarizes new information about both timing of exposure and symptoms of sexually transmitted Zika virus disease, and results of semen testing for Zika virus from 2 male travelers.

Characteristics of Children Aged <18 Years with Zika Virus Disease Acquired Postnatally - U.S. States, January 2015-July 2016.

Zika virus is an emerging mosquito-borne flavivirus that typically causes an asymptomatic infection or mild illness, although infection during pregnancy is a cause of microcephaly and other serious brain abnormalities. Guillain-Barré syndrome and other neurologic complications can occur in adults after Zika virus infection. However, there are few published reports describing postnatally acquired Zika virus disease among children. During January 2015-July 2016, a total of 158 cases of confirmed or probable postnatally acquired Zika virus disease among children aged <18 years were reported to CDC from U.S. states. The median age was 14 years (range = 1 month-17 years), and 88 (56%) were female. Two (1%) patients were hospitalized; none developed Guillain-Barré syndrome, and none died. All reported cases were travel-associated. Overall, 129 (82%) children had rash, 87 (55%) had fever, 45 (29%) had conjunctivitis, and 44 (28%) had arthralgia. Health care providers should consider a diagnosis of Zika virus disease in children who have an epidemiologic risk factor and clinically compatible illness, and should report cases to their state or local health department.

Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection - United States, August 2016.

CDC has updated its interim guidance for U.S. health care providers caring for infants born to mothers with possible Zika virus infection during pregnancy (1). Laboratory testing is recommended for 1) infants born to mothers with laboratory evidence of Zika virus infection during pregnancy and 2) infants who have abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission, regardless of maternal Zika virus test results. Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes microcephaly, intracranial calcifications or other brain anomalies, or eye anomalies, among others (2). Recommended infant laboratory evaluation includes both molecular (real-time reverse transcription-polymerase chain reaction [rRT-PCR]) and serologic (immunoglobulin M [IgM]) testing. Initial samples should be collected directly from the infant in the first 2 days of life, if possible; testing of cord blood is not recommended. A positive infant serum or urine rRT-PCR test result confirms congenital Zika virus infection. Positive Zika virus IgM testing, with a negative rRT-PCR result, indicates probable congenital Zika virus infection. In addition to infant Zika virus testing, initial evaluation of all infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should include a comprehensive physical examination, including a neurologic examination, postnatal head ultrasound, and standard newborn hearing screen. Infants with laboratory evidence of congenital Zika virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) testing before 1 month of age. Recommendations for follow-up of infants with laboratory evidence of congenital Zika virus infection depend on whether abnormalities consistent with congenital Zika syndrome are present. Infants with abnormalities consistent with congenital Zika syndrome should have a coordinated evaluation by multiple specialists within the first month of life; additional evaluations will be needed within the first year of life, including assessments of vision, hearing, feeding, growth, and neurodevelopmental and endocrine function. Families and caregivers will also need ongoing psychosocial support and assistance with coordination of care. Infants with laboratory evidence of congenital Zika virus infection without apparent abnormalities should have ongoing developmental monitoring and screening by the primary care provider; repeat hearing testing is recommended. This guidance will be updated when additional information becomes available.

Patterns in Zika Virus Testing and Infection, by Report of Symptoms and Pregnancy Status - United States, January 3-March 5, 2016.

CDC recommends Zika virus testing for potentially exposed persons with signs or symptoms consistent with Zika virus disease, and recommends that health care providers offer testing to asymptomatic pregnant women within 12 weeks of exposure. During January 3-March 5, 2016, Zika virus testing was performed for 4,534 persons who traveled to or moved from areas with active Zika virus transmission; 3,335 (73.6%) were pregnant women. Among persons who received testing, 1,541 (34.0%) reported at least one Zika virus-associated sign or symptom (e.g., fever, rash, arthralgia, or conjunctivitis), 436 (9.6%) reported at least one other clinical sign or symptom only, and 2,557 (56.4%) reported no signs or symptoms. Among 1,541 persons with one or more Zika virus-associated symptoms who received testing, 182 (11.8%) had confirmed Zika virus infection. Among the 2,557 asymptomatic persons who received testing, 2,425 (94.8%) were pregnant women, seven (0.3%) of whom had confirmed Zika virus infection. Although risk for Zika virus infection might vary based on exposure-related factors (e.g., location and duration of travel), in the current setting in U.S. states, where there is no local transmission, most asymptomatic pregnant women who receive testing do not have Zika virus infection.

Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus--United States, 2016.

CDC issued interim guidance for the prevention of sexual transmission of Zika virus on February 5, 2016. The following recommendations apply to men who have traveled to or reside in areas with active Zika virus transmission and their female or male sex partners. These recommendations replace the previously issued recommendations and are updated to include time intervals after travel to areas with active Zika virus transmission or after Zika virus infection for taking precautions to reduce the risk for sexual transmission. This guidance defines potential sexual exposure to Zika virus as any person who has had sex (i.e., vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who has traveled to or resides in an area with active Zika virus transmission. This guidance will be updated as more information becomes available.

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure--United States, 2016.

CDC has updated its interim guidance for U.S. health care providers caring for women of reproductive age with possible Zika virus exposure to include recommendations on counseling women and men with possible Zika virus exposure who are interested in conceiving. This guidance is based on limited available data on persistence of Zika virus RNA in blood and semen. Women who have Zika virus disease should wait at least 8 weeks after symptom onset to attempt conception, and men with Zika virus disease should wait at least 6 months after symptom onset to attempt conception. Women and men with possible exposure to Zika virus but without clinical illness consistent with Zika virus disease should wait at least 8 weeks after exposure to attempt conception. Possible exposure to Zika virus is defined as travel to or residence in an area of active Zika virus transmission ( http://www.cdc.gov/zika/geo/active-countries.html), or sex (vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who traveled to or resided in an area of active transmission. Women and men who reside in areas of active Zika virus transmission should talk with their health care provider about attempting conception. This guidance also provides updated recommendations on testing of pregnant women with possible Zika virus exposure. These recommendations will be updated when additional data become available.

Travel-Associated Zika Virus Disease Cases Among U.S. Residents--United States, January 2015-February 2016.

Zika virus is an emerging mosquito-borne flavivirus. Recent outbreaks of Zika virus disease in the Pacific Islands and the Region of the Americas have identified new modes of transmission and clinical manifestations, including adverse pregnancy outcomes. However, data on the epidemiology and clinical findings of laboratory-confirmed Zika virus disease remain limited. During January 1, 2015-February 26, 2016, a total of 116 residents of 33 U.S. states and the District of Columbia had laboratory evidence of recent Zika virus infection based on testing performed at CDC. Cases include one congenital infection and 115 persons who reported recent travel to areas with active Zika virus transmission (n = 110) or sexual contact with such a traveler (n = 5). All 115 patients had clinical illness, with the most common signs and symptoms being rash (98%; n = 113), fever (82%; 94), and arthralgia (66%; 76). Health care providers should educate patients, particularly pregnant women, about the risks for, and measures to prevent, infection with Zika virus and other mosquito-borne viruses. Zika virus disease should be considered in patients with acute onset of fever, rash, arthralgia, or conjunctivitis, who traveled to areas with ongoing Zika virus transmission (http://www.cdc.gov/zika/geo/index.html) or who had unprotected sex with a person who traveled to one of those areas and developed compatible symptoms within 2 weeks of returning.

Transmission of Zika Virus Through Sexual Contact with Travelers to Areas of Ongoing Transmission - Continental United States, 2016.

Zika virus is a flavivirus closely related to dengue, West Nile, and yellow fever viruses. Although spread is primarily by Aedes species mosquitoes, two instances of sexual transmission of Zika virus have been reported, and replicative virus has been isolated from semen of one man with hematospermia. On February 5, 2016, CDC published recommendations for preventing sexual transmission of Zika virus. Updated prevention guidelines were published on February 23. During February 6-22, 2016, CDC received reports of 14 instances of suspected sexual transmission of Zika virus. Among these, two laboratory-confirmed cases and four probable cases of Zika virus disease have been identified among women whose only known risk factor was sexual contact with a symptomatic male partner with recent travel to an area with ongoing Zika virus transmission. Two instances have been excluded based on additional information, and six others are still under investigation. State, territorial, and local public health departments, clinicians, and the public should be aware of current recommendations for preventing sexual transmission of Zika virus, particularly to pregnant women. Men who reside in or have traveled to an area of ongoing Zika virus transmission and have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex with their pregnant partner for the duration of the pregnancy.

Update: Influenza Activity--United States, October 4, 2015-February 6, 2016.

From October through mid-December 2015, influenza activity remained low in most regions of the United States. Activity began to increase in late December 2015 and continued to increase slowly through early February 2016. Influenza A viruses have been most frequently identified, with influenza A (H3N2) viruses predominating during October until early December, and influenza A (H1N1)pdm09 viruses predominating from mid-December until early February. Most of the influenza viruses characterized during that time are antigenically similar to vaccine virus strains recommended for inclusion in the 2015-16 Northern Hemisphere vaccines. This report summarizes U.S. influenza activity* during October 4, 2015-February 6, 2016, and updates the previous summary (1).

Antibody responses among adolescent females receiving the quadrivalent HPV vaccine series corresponding to standard or non-standard dosing intervals.

Quadrivalent human papillomavirus vaccine (HPV4) is recommended as a 3-dose series administered at 0, 1-2, and 6 months. However, this dosing schedule is often not followed leading to longer dosing intervals. We conducted a prospective study to assess antibody titers to HPV4 when dose 2 and/or dose 3 were administered on schedule or delayed. Healthy females (N=331) aged 9-18 years were enrolled at the time of receipt of HPV4 dose 2 or 3. Participants were classified as belonging to one of four groups depending upon timing of receipt of HPV4: both doses on time; only dose 2 delayed later than 90 days; only dose 3 delayed later than 180 days; or both doses 2 and 3 delayed. Pre- and post-dose 3 blood samples were assayed for HPV antibody titers (types 6, 11, 16, and 18). Post-dose 3 geometric mean titers (GMTs) for all HPV types were not significantly lower for any of the delayed dosing groups when compared to the on time group. When compared to the on time group, the post dose 3 GMTs in the delayed dose 3 group were significantly higher (p<0.05) for HPV types 6, 11, and 16. Our findings suggest that delays of dose 2 or 3 do not interfere with immune responses after completion of the 3-dose series. These results support current recommendations to not administer additional doses of HPV4 vaccine if dose 2, dose 3, or both doses have been administered late.

HIV infection and testing among Latino men who have sex with men in the United States: the role of location of birth and other social determinants.

In the United States, Latino men who have sex with men (MSM) are disproportionately affected by HIV. Latino MSM are a diverse group who differ culturally based on their countries or regions of birth and their time in the United States. We assessed differences in HIV prevalence and testing among Latino MSM by location of birth, time since arrival, and other social determinants of health.

Diagnosis of pyridoxine-dependent seizures in a nineteen-year-old patient.

Although a diagnosis of pyridoxine-dependent seizures may commonly be delayed, this case involves an extremely late diagnosis with associated morbidity. Our patient received pyridoxine during the neonatal period, in conjunction with other antiepileptic drugs that masked its effect. This patient also underwent ventriculoperitoneal shunting, which complicated the diagnosis. Pyridoxine was continued with other antiepileptic drugs, without definite recognition of its therapeutic relationship. Pyridoxine-dependent seizures were finally recognized at age 19 years when the patient manifested refractory status epilepticus, several days after wisdom tooth removal (and discontinuing oral medications including pyridoxine and phenobarbital before surgery). The diagnosis was only established via genetic testing. Our patient highlights the difficulty in diagnosing this rare seizure type and its potential importance in refractory epilepsy.

Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.

CD8(+) T cells in chronic viral infections such as HIV develop functional defects including loss of interleukin-2 (IL-2) secretion and decreased proliferative potential that are collectively termed 'exhaustion'. Exhausted T cells express increased amounts of multiple inhibitory receptors, such as programmed death-1 (PD-1), that contribute to impaired virus-specific T cell function. Although reversing PD-1 inhibition is therefore an attractive therapeutic strategy, the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 also acts by upregulating genes in exhausted T cells that impair their function. Here we analyzed gene expression profiles from HIV-specific CD8(+) T cells in individuals with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8(+) T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, whereas BATF knockdown reduced PD-1 inhibition. Silencing BATF in T cells from individuals with chronic viremia rescued HIV-specific T cell function. Thus, inhibitory receptors can cause T cell exhaustion by upregulating genes--such as BATF--that inhibit T cell function. Such genes may provide new therapeutic opportunities to improve T cell immunity to HIV.

CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans.

CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown.

High-throughput gene expression profiling of memory differentiation in primary human T cells.

The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1) the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2) a suitable cell-line representative of naive T cells.

After 'Unit 1421': an exploratory study into female students' attitudes and behaviours towards binge drinking at Leeds University.

Binge drinking has been highlighted as a growing problem in the UK, particularly amongst females aged 18-25 years. University of Leeds is situated within a population that has one of the highest reported statistics of binge drinking in the UK. In September 2006, the 'Unit 1421' campaign was launched at University of Leeds with the aim to promoted sensible drinking amongst students. The aim of this study is to explore female perspectives on binge drinking and on 'Unit 1421' campaign in the University of Leeds.

Hypoxic ventilatory responses in rats after hypercapnic hyperoxia and intermittent hyperoxia.

Perinatal hyperoxia attenuates the adult hypoxic ventilatory response in rats. Hyperoxia might elicit this plasticity by inhibiting chemoreceptor activity during early life. Thus, we hypothesized that stimulating chemoreceptors with CO(2) during hyperoxia or interrupting hyperoxia with periods of normoxia would reduce the effects of hyperoxia on the hypoxic ventilatory response. Rats were born and raised in 60% O(2) for the first two postnatal weeks. Two groups were simultaneously exposed to either sustained hypercapnia (5% CO(2)) or intermittent hypercapnia (alternating 1-h exposures to 0 and 7.5% CO(2)) while another group was exposed to only intermittent hyperoxia (alternating 1-h exposures to 21 and 60% O(2)). Hypoxic ventilatory responses were assessed at 6-10 weeks of age by whole-body plethysmography. Rats exposed to intermittent hypercapnia during hyperoxia or to intermittent hyperoxia exhibited greater increases in ventilation-to-metabolism ratio ( VE/VO2 ) in response to 12.5% O(2) than rats exposed to hyperoxia alone (both P<0.05), although responses were generally less than those of normoxia-reared controls; a similar trend was observed for rats exposed to sustained hypercapnia during hyperoxia (P=0.053). These data suggest that activity-dependent mechanisms contribute to hyperoxia-induced developmental plasticity, although contributions from additional mechanisms cannot be excluded.