Justin R. Ortiz

Influenza vaccination of pregnant women and protection of their infants.

BACKGROUND There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. METHODS We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples. RESULTS The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). CONCLUSIONS Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.).

Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends

Background Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. Methods and Findings Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearsons correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearsons correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). Conclusions This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.

Strategy to enhance influenza surveillance worldwide.

Sentinel surveillance for severe acute respiratory infection and influenza-like illness is effective in resource-limited settings.

Lack of Evidence of Avian-to-Human Transmission of Avian Influenza A (H5N1) Virus among Poultry Workers, Kano, Nigeria, 2006

BACKGROUND In February 2006, poultry outbreaks of highly pathogenic avian influenza A (H5N1) virus were confirmed in Nigeria. A serosurvey was conducted to assess H5N1 transmission among poultry workers and laboratory workers in Nigeria. METHODS From 21 March through 3 April 2006, 295 poultry workers and 25 laboratory workers with suspected exposure to H5N1 virus were administered a questionnaire to assess H5N1 exposures, medical history, and health care utilization. A serum specimen was collected from participants to test for H5N1 neutralizing antibodies by microneutralization assay. RESULTS The 295 poultry workers reported a median of 14 days of exposure to suspected or confirmed H5N1-infected poultry without antiviral chemoprophylaxis and with minimal personal protective equipment. Among 25 laboratory workers, all handled poultry specimens with suspected H5N1 virus infection. All participants tested negative for H5N1 neutralizing antibodies. CONCLUSIONS Despite widespread exposure to poultry likely infected with H5N1 virus, no serological evidence of H5N1 virus infection was identified among participants. Continued surveillance for H5N1 cases in humans and further seroprevalence investigations are needed to assess the risk of avian-to-human transmission, given that H5N1 viruses continue to circulate and evolve among poultry.

Influenza vaccine for pregnant women in resource-constrained countries: a review of the evidence to inform policy decisions.

Seasonal influenza is responsible for three to five million severe cases of disease annually, and up to 500,000 deaths worldwide. Pregnant women and infants suffer disproportionately from severe outcomes of influenza. The excellent safety profile and reliable immunogenicity of inactivated influenza vaccine support WHO recommendations that pregnant women be vaccinated to decrease complications of influenza disease during pregnancy. Nevertheless, influenza vaccine is not routinely used in most low-and middle-income countries and is not widely used in pregnant women worldwide. Two recent prospective, controlled trials of maternal influenza vaccination in Bangladesh and US Native American reservations demonstrated that inactivated influenza vaccine given to pregnant women can decrease laboratory-confirmed influenza virus infection in their newborn children. These studies support consideration of the feasibility of targeted influenza vaccine programs in resource-constrained countries. Platforms exist for the delivery of influenza vaccine to pregnant women worldwide. Even in the least developed countries, an estimated 70% of women receive antenatal care, providing an opportunity for targeted influenza vaccination. Challenges to the introduction of maternal influenza vaccination in resource-constrained countries exist, including issues regarding vaccine formulation, availability, and cost. Nonetheless, maternal influenza vaccination remains an important and potentially cost-effective approach to decrease influenza morbidity in two high-risk groups - pregnant women and young infants.

Influenza-Associated Cystic Fibrosis Pulmonary Exacerbations

BACKGROUND Although cystic fibrosis (CF) is the most common inherited respiratory disease, the burden of influenza among individuals with CF is not well characterized. METHODS We used the CF Foundation Patient Registry to determine the relationship between pulmonary exacerbation incidence rate and influenza virus season from July 2003 through June 2007. The outcome of interest, pulmonary exacerbation, was defined as treatment of a respiratory illness with IV antibiotics. Each influenza season was defined as all months during which >/= 15% of laboratory tests for influenza virus were positive in the US influenza virologic surveillance system. We calculated incidence rates of pulmonary exacerbation during the influenza and summertime seasons as well as relative rates with 95% CIs. A multivariate regression model adjusted for demographic and clinical predictors. RESULTS In 2003, the patient cohort size was 21,506 patients, and 7,727 patients experienced at least one pulmonary exacerbation. The overall pulmonary exacerbation incidence rate in the influenza season was 595.0 per 10,000 person-months compared with a summertime baseline of 549.6 per 10,000 person-months. The incidence rate ratio was 1.08 (95% CI: 1.06, 1.10). Multivariate analysis did not change our estimate of risk (adjusted odds ratio: 1.07; 95% CI: 1.05, 1.10). An estimated annual excess of 147.6 per 10,000 person-months or an excess 2.1% of total exacerbations occur during the influenza season. CONCLUSION Our data demonstrate a substantial contribution of the influenza season to CF morbidity. Further studies to determine any causal link between influenza infection and CF pulmonary exacerbations are necessary.

Development of the respiratory index of severity in children (risc) score among young children with respiratory infections in South Africa.

Objective Pneumonia is a leading cause of death in children worldwide. A simple clinical score predicting the probability of death in a young child with lower respiratory tract infection (LRTI) could aid clinicians in case management and provide a standardized severity measure during epidemiologic studies. Methods We analyzed 4,148 LRTI hospitalizations in children <24 months enrolled in a pneumococcal conjugate vaccine trial in South Africa from 1998–2001, to develop the Respiratory Index of Severity in Children (RISC). Using clinical data at admission, a multivariable logistic regression model for mortality was developed and statistically evaluated using bootstrap resampling techniques. Points were assigned to risk factors based on their coefficients in the multivariable model. A childs RISC score is the sum of points for each risk factor present. Separate models were developed for HIV-infected and non-infected children. Results Significant risk factors for HIV-infected and non-infected children included low oxygen saturation, chest indrawing, wheezing, and refusal to feed. The models also included age and HIV clinical classification (for HIV-infected children) or weight-for-age (for non-infected children). RISC scores ranged up to 7 points for HIV-infected or 6 points for non-infected children and correlated with probability of death (0–47%, HIV-infected; 0–14%, non-infected). Final models showed good discrimination (area under the ROC curve) and calibration (goodness-of-fit). Conclusion The RISC score incorporates a simple set of risk factors that accurately discriminate between young children based on their risk of death from LRTI, and may provide an objective means to quantify severity based on the risk of mortality.

The Burden of Influenza-Associated Critical Illness Hospitalizations*

Objective: Influenza is the most common vaccine-preventable disease in the United States; however, little is known about the burden of critical illness due to influenza virus infection. Our primary objective was to estimate the proportion of all critical illness hospitalizations that are attributable to seasonal influenza. Design: Retrospective cohort study. Setting: Arizona, California, and Washington from January 2003 to March 2009. Patients: All adults hospitalized with critical illness, defined by International Classification of Diseases, 9th Edition, Clinical Modification diagnosis and procedure codes for acute respiratory failure, severe sepsis, or in-hospital death. Measurements and Main Results: We combined the complete hospitalization discharge databases for three U.S. states, regional influenza virus surveillance, and state census data. Using negative binomial regression models, we estimated the incidence rates of adult influenza-associated critical illness hospitalizations and compared them with all-cause event rates. We also compared modeled outcomes to International Classification of Diseases, 9th Edition, Clinical Modification–coded influenza hospitalizations to assess potential underrecognition of severe influenza disease. During the study period, we estimated that 26,760 influenza-associated critical illness hospitalizations (95% CI, 14,541, 47,464) occurred. The population-based incidence estimate for influenza-associated critical illness was 12.0 per 100,000 person-years (95% CI, 6.6, 21.6) or 1.3% of all critical illness hospitalizations (95% CI, 0.7%, 2.3%). During the influenza season, 3.4% of all critical illness hospitalizations (95% CI, 1.9%, 5.8%) were attributable to influenza. There were only 2,612 critical illness hospitalizations with International Classification of Diseases, 9th Edition, Clinical Modification–coded influenza diagnoses, suggesting influenza is either undiagnosed or undercoded in a substantial proportion of critical illness. Conclusions: Extrapolating our data to the 2010 U.S. population, we estimate that about 28,000 adults are hospitalized for influenza-associated critical illness annually. Influenza in many of these critically ill patients may be undiagnosed. Critical care physicians should have a high index of suspicion for influenza in the ICU, particularly when influenza is known to be circulating in their communities.

Association between Smoking and Latent Tuberculosis in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey

Background Evidence of an association between cigarette smoking and latent tuberculosis infection (LTBI) is based on studies in special populations and/or from high prevalence settings. We sought to evaluate the association between LTBI and smoking in a low prevalence TB setting using population-based data from the National Health and Nutrition Examination Survey (NHANES). Methods In 1999–2000, NHANES assessed LTBI (defined as a tuberculin skin test measurement ≥10 mm) in participants, and those ≥20 years of age were queried regarding their tobacco use and serum cotinine was measured. We evaluated the association of LTBI with self-reported smoking history and smoking intensity in multivariable logistic regression models that adjusted for known confounders (gender, age, birthplace, race/ethnicity, poverty, education, history of BCG vaccination, and history of household exposure to tuberculosis disease). Results Estimated LTBI prevalence was 5.3% among those ≥20 years of age. The LTBI prevalence among never smokers, current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI, 1.1–2.9). The association between smoking and LTBI was strongest for Mexican-American and black individuals. In multivariate analysis stratified by race/ethnicity, cigarette packs per day among Mexican-American smokers and cotinine levels among black smokers, were significantly associated with LTBI. Conclusions In the large, representative, population-based NHANES sample, smoking was independently associated with significantly increased risks of LTBI. In certain populations, a greater risk of LTBI corresponded with increased smoking exposure.

A global review of national influenza immunization policies: Analysis of the 2014 WHO/UNICEF Joint Reporting Form on immunization.

Introduction The WHO recommends annual influenza vaccination to prevent influenza illness in high-risk groups. Little is known about national influenza immunization policies globally. Material and Methods The 2014 WHO/UNICEF Joint Reporting Form (JRF) on Immunization was adapted to capture data on influenza immunization policies. We combined this dataset with additional JRF information on new vaccine introductions and strength of immunization programmes, as well as publicly available data on country economic status. Data from countries that did not complete the JRF were sought through additional sources. We described data on country influenza immunization policies and used bivariate analyses to identify factors associated with having such policies. Results Of 194 WHO Member States, 115 (59%) reported having a national influenza immunization policy in 2014. Among countries with a national policy, programmes target specific WHO-defined risk groups, including pregnant women (42%), young children (28%), adults with chronic illnesses (46%), the elderly (45%), and health care workers (47%). The Americas, Europe, and Western Pacific were the WHO regions that had the highest percentages of countries reporting that they had national influenza immunization policies. Compared to countries without policies, countries with policies were significantly more likely to have the following characteristics: to be high or upper middle income (p < 0.0001); to have introduced birth dose hepatitis B virus vaccine (p < 0.0001), pneumococcal conjugate vaccine (p = 0.032), or human papilloma virus vaccine (p = 0.002); to have achieved global goals for diphtheria-tetanus-pertussis vaccine coverage (p < 0.0001); and to have a functioning National Immunization Technical Advisory Group (p < 0.0001). Conclusions The 2014 revision of the JRF permitted a global assessment of national influenza immunization policies. The 59% of countries reporting that they had policies are wealthier, use more new or under-utilized vaccines, and have stronger immunization systems. Addressing disparities in public health resources and strengthening immunization systems may facilitate influenza vaccine introduction and use.