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Susan L Hills - Top 30 Publications

Ability to serologically confirm recent Zika virus infection in areas with varying past incidence of dengue virus infection - United States and territories, 2016.

Background. Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive IgM results in areas with varying past dengue virus (DENV) infection incidence. Methods. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from January 1 through August 31, 2016 with positive ZIKAV IgM results and ZIKAV and DENV PRNT performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false-positive for samples interpreted as DENV infection or negative. Results. In US states, 208 (27%) of 759 IgM positives were confirmed as ZIKAV, compared to 11 (21%) of 52 in the US Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM positives were unspecified flavivirus infections. The false-positivity rate was 27% in US states, 18% in USVI, 2% in American Samoa, and 6% in Puerto Rico. Conclusions. In US states, PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM positive samples. Almost a third of ZIKAV IgM positive results did not confirm; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher DENV transmission, PRNT usually could not differentiate between ZIKAV and DENV infections.

Updated estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in Nepal.

Japanese encephalitis (JE) is a mosquito-borne disease that is associated with considerable morbidity and mortality in many Asian countries. The objective of this study was to describe the impact of the JE immunization program using SA 14-14-2 JE vaccine implemented in Nepal during 2006 through 2011. A previous assessment after the initial program implementation phase described a significantly lower post-campaign JE incidence compared to expected incidence; however, the previous evaluation had limited post-campaign data for some districts.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Establishing a Timeline to Discontinue Routine Testing of Asymptomatic Pregnant Women for Zika Virus Infection - American Samoa, 2016-2017.

The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016 (1). In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures (1), strategies to protect pregnant women (1), syndromic surveillance based on electronic health record (EHR) reports (1), Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis) (1-3), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance (2,3)(.) All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January-February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance (1) indicated a return to pre-outbreak levels. The last Zika virus disease case detected by real-time, reverse transcription-polymerase chain reaction (rRT-PCR) occurred in a patient who had symptom onset on June 19, 2016. In August 2016, ASDoH requested CDC support in assessing whether local transmission had been reduced or interrupted and in proposing a timeline for discontinuation of routine testing of asymptomatic pregnant women. An end date (October 15, 2016) was determined for active mosquito-borne transmission of Zika virus and a timeline was developed for discontinuation of routine screening of asymptomatic pregnant women in American Samoa (conception after December 10, 2016, with permissive testing for asymptomatic women who conceive through April 15, 2017).

Chikungunya virus disease outbreak in Yap State, Federated States of Micronesia.

Chikungunya virus is a mosquito-borne alphavirus which causes an acute febrile illness associated with polyarthralgia. Beginning in August 2013, clinicians from the Yap State Department of Health in the Federated States of Micronesia (FSM) identified an unusual cluster of illness which was subsequently confirmed to be chikungunya virus disease. Chikungunya virus disease previously had not been recognized in FSM.

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.

Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure - United States, September 2016.

CDC has updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive (1) and interim guidance to prevent transmission of Zika virus through sexual contact (2), now combined into a single document. Guidance for care for pregnant women with possible Zika virus exposure was previously published (3). Possible Zika virus exposure is defined as travel to or residence in an area of active Zika virus transmission (, or sex* without a condom(†) with a partner who traveled to or lived in an area of active transmission. Based on new though limited data, CDC now recommends that all men with possible Zika virus exposure who are considering attempting conception with their partner, regardless of symptom status,(§) wait to conceive until at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Recommendations for women planning to conceive remain unchanged: women with possible Zika virus exposure are recommended to wait to conceive until at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Couples with possible Zika virus exposure, who are not pregnant and do not plan to become pregnant, who want to minimize their risk for sexual transmission of Zika virus should use a condom or abstain from sex for the same periods for men and women described above. Women of reproductive age who have had or anticipate future Zika virus exposure who do not want to become pregnant should use the most effective contraceptive method that can be used correctly and consistently. These recommendations will be further updated when additional data become available.

Zika Virus Disease Cases - 50 States and the District of Columbia, January 1-July 31, 2016.

Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections have also been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-5). Most Zika virus infections are asymptomatic (1,6). Clinical illness, when it occurs, is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. However, Zika virus infection during pregnancy can cause adverse outcomes such as fetal loss, and microcephaly and other serious brain anomalies (1-3). Guillain-Barré syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection (1). Following the identification of local transmission of Zika virus in Brazil in May 2015, the virus has continued to spread throughout the Region of the Americas, and travel-associated cases have increased (7). In 2016, Zika virus disease and congenital infections became nationally notifiable conditions in the United States (8). As of September 3, 2016, a total of 2,382 confirmed and probable cases of Zika virus disease with symptom onset during January 1-July 31, 2016, had been reported from 48 of 50 U.S. states and the District of Columbia. Most cases (2,354; 99%) were travel-associated, with either direct travel or an epidemiologic link to a traveler to a Zika virus-affected area. Twenty-eight (1%) cases were reported as locally acquired, including 26 associated with mosquito-borne transmission, one acquired in a laboratory, and one with an unknown mode of transmission. Zika virus disease should be considered in patients with compatible clinical signs or symptoms who traveled to or reside in areas with ongoing Zika virus transmission or who had unprotected sex with someone who traveled to those areas. Health care providers should continue to educate patients, especially pregnant women, about the importance of avoiding infection with Zika virus, and all pregnant women should be assessed for possible Zika virus exposure at each prenatal visit (2).

Zika and the Risk of Microcephaly.

Projecting Month of Birth for At-Risk Infants after Zika Virus Disease Outbreaks.

The marked increase in infants born with microcephaly in Brazil after a 2015 outbreak of Zika virus (Zika virus) disease suggests an association between maternal Zika virus infection and congenital microcephaly. To project the timing of delivery of infants born to mothers infected during early pregnancy in 1 city in Bahia State, Brazil, we incorporated data on reported Zika virus disease cases and microcephaly cases into a graphical schematic of weekly birth cohorts. We projected that these births would occur through February 2016. Applying similar projections to a hypothetical location at which Zika virus transmission started in November, we projected that full-term infants at risk for Zika virus infection would be born during April-September 2016. We also developed a modifiable spreadsheet tool that public health officials and researchers can use for their countries to plan for deliveries of infants to women who were infected with Zika virus during different pregnancy trimesters.

Zika Virus Infection Among U.S. Pregnant Travelers - August 2015-February 2016.

After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area, and an update was released on February 5. As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management. Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website.

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.

Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2009-2012.

In March 2009, the U.S. Food and Drug Administration licensed an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [Ixiaro]) for use in adults. The vaccine was licensed based on clinical trial safety data in 3558 JE-VC recipients. It is essential to monitor post-licensure surveillance data to evaluate the safety of JE-VC because rare adverse events may not be detected until the vaccine is administered to a larger population.

Use of Japanese encephalitis vaccine in US travel medicine practices in Global TravEpiNet.

Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices.

A case series of three US adults with Japanese encephalitis, 2010-2012.

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia. Although the risk for acquiring JE for most travelers to Asia is low, it varies based on the destination, season, trip duration, and activities.

Effect of aerial insecticide spraying on West Nile virus disease--north-central Texas, 2012.

During 2012, four north-central Texas counties experienced high West Nile virus (WNV) disease incidence. Aerial insecticide spraying was conducted in two counties. To evaluate the effect of spraying on WNV disease, we calculated incidence rate ratios (IRRs) in treated and untreated areas by comparing incidence before and after spraying; for unsprayed areas, before and after periods were defined by using dates from a corresponding sprayed area. In treated areas, WNV neuroinvasive disease incidence before and after spraying was 7.31/100,000 persons and 0.28/100,000 persons, respectively; the IRR was 26.42 (95% confidence interval [CI]: 12.42-56.20). In untreated areas, the before and after incidence was 4.80/100,000 persons and 0.45/100,000 persons, respectively; the IRR was 10.57 (95% CI: 6.11-18.28). The ratio of IRRs was 2.50 (95% CI: 0.98-6.35). Disease incidence decreased in both areas, but the relative change was greater in aerial-sprayed areas.

Estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in Nepal.

Wider availability of the live, attenuated SA 14-14-2 Japanese encephalitis (JE) vaccine has facilitated introduction or expansion of immunization programs in many countries. However, information on their impact is limited. In 2006, Nepal launched a JE immunization program, and by 2009, mass campaigns had been implemented in 23 districts. To describe the impact, we analyzed surveillance data from 2004 to 2009 on laboratory-confirmed JE and clinical acute encephalitis syndrome (AES) cases. The post-campaign JE incidence rate of 1.3 per 100,000 population was 72% lower than expected if no campaigns had occurred, and an estimated 891 JE cases were prevented. In addition, AES incidence was 58% lower, with an estimated 2,787 AES cases prevented, suggesting that three times as many disease cases may have been prevented than indicated by the laboratory-confirmed JE cases alone. These results provide useful information on preventable JE disease burden and the potential value of JE immunization programs.

Estimated global incidence of Japanese encephalitis: a systematic review.

To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts.

Surveillance for Japanese encephalitis in Vietnam, 1998-2007.

Japanese encephalitis (JE) is recognized as an important public health problem in Vietnam. A JE immunization program was introduced in 1997 in high-risk districts and expanded to additional districts over subsequent years. We reviewed national acute encephalitis syndrome (AES) surveillance data for 1998-2007 and analyzed more detailed data regarding JE from five northern provinces in 2004 and 2005. The annual reported incidence of AES in Vietnam ranged from 3.0 to 1.4 cases per 100,000 population with a decreasing trend over the 10-year period. The mean annual incidence of AES was highest in the northern region of the country. Of 421 AES cases from five northern provinces with laboratory results reported, 217 (52%) had laboratory evidence of recent JEV infection. As Vietnam moves closer to control of JE through immunization, accurate JE surveillance data will be important to evaluate and guide the program.

Japanese encephalitis in travelers from non-endemic countries, 1973-2008.

Japanese encephalitis (JE) is a severe disease and a risk for travelers who visit JE-endemic countries. We reviewed all published JE cases in travelers from non-endemic areas from 1973 through 2008, and assessed factors related to risk of infection. There were 55 cases that occurred in citizens of 17 countries. Age range of case-patients was 1-91 years (median = 34 years). Ten (18%) persons died and 24 (44%) had mild to severe sequelae. In a detailed risk assessment of 37 case-patients, 24 (65%) had spent > or = 1 month in JE-endemic areas, and most had factors identified that may have increased infection risk. The estimate of overall JE risk was low, < 1 case/1 million travelers to JE-endemic countries. Nonetheless, for each traveler, a careful assessment of itinerary and activities, a decision on vaccination, and information on mosquito precautions are needed to reduce the risk of this disease.

Disability from Japanese encephalitis in Cambodia and Viet Nam.

A cohort of Japanese encephalitis (JE) survivors in Cambodia and Viet Nam were assessed at least 4 months after hospital discharge in order to understand the extent of disability after JE. We used a simple assessment tool which focuses on the impact on daily life. In total, 64 disability assessments were conducted: 38 in Cambodia and 26 in Viet Nam. In Cambodia, 4 (11%) children had severe sequelae, suggesting the children would likely be dependent, 15 (39%) had moderate sequelae and 17 (45%) had mild sequelae. In Viet Nam, two (8%) persons had severe sequelae, five (19%) had moderate sequelae and eight (31%) had mild sequelae. In many JE-endemic areas there are no multi-disciplinary teams with sophisticated equipment to assess patients after JE disease. This assessment tool can assist with patient management and generate data to support the need for programmes to prevent disease and improve outcomes for survivors.

Past, present, and future of Japanese encephalitis.

Outcome and extent of disability following Japanese encephalitis in Indonesian children.

The study aimed to assess outcome, including level of disability, following Japanese encephalitis (JE) in children in Indonesia.

Analysis on data from the clinical acute viral encephalitis surveillance system in three prefectures in Shaanxi during 2005 - 2006.

To describe the epidemiological features of viral encephalitis and burden of Japanese encephalitis (JE), and to identify potential strategies for effective JE control measures, using data from the Viral Encephalitis Surveillance Program (VESP) launched in Ankang, Baoji, and Weinan prefectures, Shaanxi province.

Confirmation of Japanese encephalitis as an endemic human disease through sentinel surveillance in Indonesia.

Japanese encephalitis (JE) results in significant mortality and disability in children in Asia. In Indonesia, despite recognition of JE virus transmission, reports of human disease have been few and from limited geographic areas. Hospital-based surveillance for acute encephalitis syndrome (AES) and JE in children 15 years of age and under was undertaken in 15 hospitals in six provinces from 2005 to 2006. High- and low-risk provinces in geographically dispersed areas were included. Health center-based surveillance also was undertaken in one province. Eighty-two JE cases were confirmed among 1,496 AES cases detected. JE cases were confirmed in all provinces, but the proportion varied between 18% and 2% among provinces of different risk levels. Children younger than 10 years of age represented 95% of JE cases, and 47% of all cases either died or were disabled. The study shows JE is an endemic human disease across Indonesia. Immunization strategies are being considered.

Evaluation of three immunoglobulin M antibody capture enzyme-linked immunosorbent assays for diagnosis of Japanese encephalitis.

Japanese encephalitis (JE) virus is a major cause of neurologic infection in Asia, but surveillance has been limited. Three JE immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay kits have recently been developed. The aim of this study was to evaluate their sensitivity, specificity, and usability using 360 acute-phase serum samples containing JE, dengue, or neither IgM antibody. The kits, manufactured by Panbio Limited, Inbios International, Inc., and XCyton Diagnostics Ltd, had high sensitivities of 89.3%, 99.2%, and 96.7%, respectively. The specificities were 99.2%, 56.1%, and 65.3%, respectively. When dengue IgM-positive samples were excluded, the kits had specificities of 98.4%, 96.1%, and 96.1%, respectively. The Panbio kit includes both JE and dengue antigens and appears to have an advantage in settings where dengue virus co-circulates, although further assessments in clinical settings are needed. This information is helpful in considering options for strengthening the laboratory component of JE surveillance.

Impact of hepatitis A vaccination of Indigenous children on notifications of hepatitis A in north Queensland.

To describe the impact of a hepatitis A vaccination program for Indigenous children in north Queensland.

Dengue in north Queensland, 2002.

In 2002 three separate outbreaks of dengue were detected in north Queensland, including the first documented outbreak of dengue 4 in Australia. Molecular analyses identified Thailand and Indonesia as the likely origin of two of the outbreaks. Investigations during 2002 also included a suspected dengue outbreak in the Torres Strait which proved to be a false alarm, and a number of imported cases of dengue in north Queensland.

Melioidosis in northern Australia, 2001-02.

Melioidosis, caused by the gram negative bacterium Burkholderia pseudomallei, is endemic in northern Australia. Using data collated from centres in Western Australia, the Northern Territory and Queensland, this report describes the epidemiology of this disease between 1 November, 2001 and 31 October, 2002. There were 47 cases seen during this period with an average annual incidence of 5.8 cases per 100,000 population. In Indigenous Australians, an incidence of 25.5 cases per 100,000 population was seen. The timing and location of cases was generally correlated with rainfall across northern Australia. A case-cluster in a Queensland community was associated with post-cyclonic flooding. Risk factors included diabetes, alcohol-related problems and renal disease. Pneumonia (51%) was the most common clinical diagnosis. The mortality rate attributable to melioidosis was 21 per cent, although a number of other patients died of underlying disease. Despite improvements in recognition and treatment, melioidosis is still associated with a high morbidity and mortality, particularly in Indigenous Australians.

A focal, rapidly-controlled outbreak of dengue fever in two suburbs in Townsville, north Queensland, 2001.

In April-May 2001 an outbreak of dengue fever occurred in two suburbs in Townsville, north Queensland. This was the first outbreak in the Townsville region since a very large outbreak in 1992-1993. Notification delays resulted in late detection of the outbreak. Once recognised, control measures were implemented and rapid control was achieved. Dengue serotype 2 was the causative virus and 9 cases of dengue fever were documented. The approach to management of dengue fever outbreaks and vector control strategies have been improved and refined in the years since the 1992-1993 outbreak. These measures, in addition to favourable weather conditions, were likely to have contributed to the successful containment of this outbreak.