Zika Virus: A Brief History and Review of Its Pathogenesis Rediscovered.

From its discovery in Uganda in 1947, Zika virus (ZIKV) was considered a relatively innocuous viral pathogen with sporadic and infrequent occurrence of human infection. It was during an outbreak in French Polynesia in 2014 when cases of Guillain-Barré syndrome were identified as a serious complication of ZIKV infection in adults. However, in 2015, ZIKV emerged into and swept through South and Central America infecting millions of people. As part of the latter ZIKV outbreak, in Brazil, cases of microcephaly and other serious congenital complications affecting a large fraction of infants born to mothers infected during pregnancy were first identified and linked to ZIKV. This chapter reviews the history and clinical manifestations of ZIKV infection and mechanisms of immunoprotection. It is notable that, while limited, historical monographs identified most, if not all, of the precepts that are considered as newly discovered.

Survival, Hospitalization, and Acute-Care Costs of Very and Moderate Preterm Infants in the First 6 Years of Life: A Population-Based Study.

OBJECTIVES: To investigate survival, hospitalization, and acute-care costs of very (28-31 weeks' gestation) and moderate preterm (32-33 weeks' gestation) infants in the first 6 years of life and compare outcomes with the more widely studied extremely preterm infants (24-27 weeks' gestation) and to full term (low risk) infants (39-40 weeks' gestation). STUDY DESIGN: Birth data from all women residing in New South Wales, Australia, with gestational ages between 24-33 and 39-40 weeks in 2001-2011 were linked probabilistically to hospitalization and mortality data. Study outcomes were evaluated with the use of descriptive and multivariable analyses at birth (N = 559,532), discharge (N = 540,240), and at 1 (N = 487,447) and 6 years of age (N = 230,498). RESULTS: Mortality was greatest among extremely preterm infants (eg, 31.2% within 6 years) and decreased with increasing gestational age. Likewise, hospitalization within the first year of life increased with decreasing gestational age (aOR 5.5 [95% CI 4.7-6.4], 3.7 [3.4-4.0], and 2.6 [2.5-2.8] for birth at 24-27, 28-31, and 32-33 weeks' gestation, relative to 39-40 weeks' gestation). Hospitalization remained significantly increased with preterm birth at each year of age up to 6 years (aORs 1.3-1.6 at 6 years). Cumulative costs were significantly greater with preterm birth within the first year of life, and also between 1 and 6 years of age. CONCLUSIONS: The risks of adverse health outcomes were significantly greater in very and moderately preterm infants relative to full term infants but lower than extremely preterm infants. Crucially, preterm birth was associated with prolonged increased odds of hospitalization (up to age 6 years), contributing to greater resource use.

Site-specific predictors of successful recruitment to a perinatal clinical trial.

BACKGROUND: With large collaborations needed to reach sample size requirements for relatively rare events, a major challenge for multi-centre clinical trials is efficiency of recruitment at individual sites. We used data from an international, multi-centre, randomised trial of preterm prelabour rupture of membranes to assess any impact on recruitment following the introduction of a new Clinical Trial Agreement and to identify site-specific predictors of recruitment to the trial for the purpose of targeting future recruitment sites and strategies. METHODS: The outcome measure was recruitment rate per 10,000 births, and according to this, an average recruitment rate was determined. Factors that were considered potentially predictive of recruitment above the average rate were classified according to three broad themes: 'ethics and regulatory requirements', 'characteristics of site investigators' and the 'research culture' at the collaborating site. Data were analysed using contingency tables and logistic regression modelling. RESULTS: At 31 January 2009, following the introduction of the Clinical Trial Agreement, 39 centres had obtained ethics approval to commence recruitment, and 38 centres had enrolled at least one woman. Time to first recruit ranged from 25 days to 584 days. Recruitment rates ranged from 0.18 to 6.0 per 10,000 births (mean 1.71/10,000 births) per month. Factors most associated with above-average recruitment rate were the following: implementation of a clearly defined 'system' of recruitment, engagement of other staff, time from ethics approval to first recruit and provision of a dedicated trial coordinator. CONCLUSION: A delay of greater than 3 months in approval of the new Clinical Trial Agreement had an effect which extended into the third year of the trial. Characteristics that were indicative of the presence of a 'system' were the best predictors of recruitment. It may be more effective to limit recruitment sites and focus resources on those sites where investigators are engaged with trial processes and have adequate resources and structures to support them.

Risk factors and costs of hospital admissions in first year of life: a population-based study.

OBJECTIVE: To identify the maternal and infant risk factors associated with hospital admission in the first year and estimate the associated costs of infant hospitalization. STUDY DESIGN: Data from the Perinatal Data Collection for 599753 liveborn infants born in New South Wales, Australia, 2001-2007 were linked to hospital admission data. Logistic regression models were used to investigate the association between maternal and infant characteristics and admission to hospital once, and more than once in the first year; and average costs for total hospital admissions were calculated. RESULTS: Almost 15% of infants were admitted to hospital once and 4.6% had multiple admissions. Gestational age <37 weeks was most strongly associated with admission to hospital once, and severe neonatal morbidity was most strongly associated with multiple admissions (aOR 2.60; 95% CI 2.47-2.75). Infants born <39 weeks gestational age, to adolescent mothers, mothers who smoke, are not married, or had a planned delivery also have an increased risk of multiple admissions. Infants with severe neonatal morbidity contributed 27% of total infant hospital costs. With each increasing week of gestational age the mean annual cost decreased on average 10% and 27% for infants with and without neonatal morbidity respectively. CONCLUSIONS: Infants born with severe neonatal morbidity have increased hospitalizations in the first year; however, the majority of burden on health system is by infants without severe neonatal morbidity. Hospitalizations, and associated costs, increased with decreasing gestational age, even for infants born at 37-38 weeks. Targeted public health strategies may reduce the burden of infant hospitalizations.

Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.

BACKGROUND: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). METHODS: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. RESULTS: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. CONCLUSIONS: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.

Urban habitat evaluation for West Nile virus surveillance in mosquitoes in Albuquerque, New Mexico.

As part of an ongoing mosquito surveillance program, 27 sites in the greater metropolitan Albuquerque area (Bernalillo County, New Mexico) were trapped from May through September 2004. Each site was sampled for 1 night weekly, using a standard CO2-baited Centers for Disease Control and Prevention light trap and a gravid trap. Captured mosquitoes were catalogued by location, species, and date, and selected pools were tested for West Nile virus (WNV) by reverse transcription-polymerase chain reaction. Based on previous surveillance, WNV was already established in the state of New Mexico. Surveillance during 2003, the 1st year of WNV detection in New Mexico mosquitoes, was focused on the bosque forest of the Rio Grande river valley. Surveillance during summer of 2004 was extended to additional areas around the city of Albuquerque, the state's largest population center. In addition to the standard surveillance objectives, a secondary goal was to determine whether foci of WNV activity were detectable in other habitats besides the riparian ecosystem of the Rio Grande, and in other species not previously identified as vectors. There was no demonstrable advantage to extending the traditional trapping area outside of the Rio Grande valley. Sites in the valley area had WNV-positive mosquitoes earlier in the season, and for a longer period than the added sites. In addition, riparian sites had the highest diversity of species, the largest numbers of Culex spp. captured, and the largest proportion of the WNV-positive mosquito pools from the study. Species found in other areas of the metropolitan area were also represented in the valley. Although WNV activity was detected in other areas of the city, its activity began later and ended earlier than in the river valley. We surmise that the greatest benefit to mosquito surveillance could be achieved by focusing on the river valley area.