Burden of Respiratory Syncytial Virus-Associated Acute Respiratory Infections During Pregnancy.

BACKGROUND: With the licensure of maternal respiratory syncytial virus (RSV) vaccines in Europe and the United States, data are needed to better characterize the burden of RSV-associated acute respiratory infections (ARI) in pregnancy. The current study aimed to determine among pregnant individuals the proportion of ARI testing positive for RSV and the RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review, following PRISMA 2020 guidelines, using 5 databases (Medline, Embase, Global Health, Web of Science, and Global Index Medicus), and including additional unpublished data. Pregnant individuals with ARI who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with ARI that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% confidence interval [CI], 1.9%-54%). The pooled incidence rate of RSV among pregnant individuals was 26.0 (95% CI, 15.8-36.2) per 1000 person-years. RSV hospitalization rates reported in 2 studies were 2.4 and 3.0 per 1000 person-years. In 5 studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in the odds of miscarriage, stillbirth, low birth weight, and small size for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio, 3.6 [95% CI, 1.3-10.3]). CONCLUSIONS: Data on RSV-associated hospitalization rates are limited, but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions.

Evaluation of cesarean delivery rates and factors associated with cesarean delivery among women enrolled in a pregnancy cohort study at two tertiary hospitals in Thailand.

BACKGROUND: Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. METHODS: In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6-8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. RESULTS: Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25-35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (< 1%). Factors independently associated with cesarean delivery included age ≥ 25 years, pre-pregnancy obesity, new/worsen medical condition during pregnancy, fetal distress, abnormal labor, infant size for gestational age ≥ 50th percentiles, and self-pay for delivery fees. Women with existing blood conditions were less likely to have cesarean delivery. CONCLUSIONS: Almost one in two pregnancies among women in our cohorts resulted in cesarean deliveries. Compared to WHO guidelines, cesarean delivery rates were elevated in selected Robson groups indicating that tailored interventions to minimize non-clinically indicated cesarean delivery for specific groups of pregnancies may be warranted.

Feasibility and Performance of Self-Collected Nasal Swabs for Detection of Influenza Virus, Respiratory Syncytial Virus, and Human Metapneumovirus.

BACKGROUND: We assessed performance of participant-collected midturbinate nasal swabs compared to study staff-collected midturbinate nasal swabs for the detection of respiratory viruses among pregnant women in Bangkok, Thailand. METHODS: We enrolled pregnant women aged ≥18 years and followed them throughout the 2018 influenza season. Women with acute respiratory illness self-collected midturbinate nasal swabs at home for influenza viruses, respiratory syncytial viruses (RSV), and human metapneumoviruses (hMPV) real-time RT-PCR testing and the study nurse collected a second midturbinate nasal swab during home visits. Paired specimens were processed and tested on the same day. RESULTS: The majority (109, 60%) of 182 participants were 20-30 years old. All 200 paired swabs had optimal specimen quality. The median time from symptom onsets to participant-collected swabs was 2 days and to staff-collected swabs was also 2 days. The median time interval between the 2 swabs was 2 hours. Compared to staff-collected swabs, the participant-collected swabs were 93% sensitive and 99% specific for influenza virus detection, 94% sensitive and 99% specific for RSV detection, and 100% sensitive and 100% specific for hMPV detection. CONCLUSIONS: Participant-collected midturbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

Performance of Symptom-Based Case Definitions to Identify Influenza Virus Infection Among Pregnant Women in Middle-Income Countries: Findings From the Pregnancy and Influenza Multinational Epidemiologic (PRIME) Study.

BACKGROUND: The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, although their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. METHODS: In 2017 and 2018, we contacted 11 277 pregnant women twice weekly during the influenza season to identify illnesses with new or worsened cough, runny nose, sore throat, difficulty breathing, or myalgia and collected data on other symptoms and nasal swabs for influenza real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. We calculated sensitivity, specificity, positive-predictive value, and negative-predictive value of each symptom predictor, WHO respiratory illness case definitions, and a de novo definition derived from results of multivariable modeling. RESULTS: Of 5444 eligible illness episodes among 3965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever ≥38°C (adjusted odds ratio [95% confidence interval], 4.6 [3.1-6.8]), myalgia (3.0 [2.2-4.0]), cough (2.7 [1.9-3.9]), and chills (1.6 [1.1-2.4]) were independently associated with influenza illness. A definition based on these 4 (measured fever, cough, chills, or myalgia) was 95% sensitive and 27% specific. The WHO influenza-like illness (ILI) definition was 16% sensitive and 98% specific. CONCLUSIONS: The current WHO ILI case definition was highly specific but had low sensitivity. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity.

Tolerability of trivalent inactivated influenza vaccine among pregnant women, 2015.

BACKGROUND: Thailand recommends influenza vaccination among pregnant women. We conducted a cohort study to determine if the prevalence of adverse events following immunization (AEFIs) with influenza vaccine among Thai pregnant women was similar to that often cited among healthy adults. METHODS: Women who were ≥17 gestational weeks and ≥18 years of age were recruited. Demographic and health history data were collected using structured questionnaires. Women were provided with symptom diary, ruler to measure local reaction(s), and thermometer to measure body temperature. AEFIs were defined as any new symptom/abnormality occurring within four weeks after vaccination. The diaries were abstracted for frequency, duration, and level of discomfort/inconvenience of the AEFIs. Serious adverse events (SAEs) and the likelihood of AEFIs being associated with vaccination were determined using standard definitions. RESULTS: Among 305 women enrolled between July-November 2015, median age was 29 years. Of these, 223 (73%) were in their third trimester, 271 (89%) had completed secondary school or higher, and 20 (7%) reported ≥1 pre-existing conditions. AEFIs were reported in 134 women (44%; 95% confidence interval [CI] 38-50%). Soreness at the injection site (74, 24%; CI 19-29%), general weakness (50, 16%; CI 12-21%), muscle ache (49, 16%; CI 12-21%), and headache (45, 15%; CI 1-19%) were most common. Of those with AEFIs, 120 (89%) reported symptom/abnormality occurred on day 0 or day 1 following vaccination. Ten women (7%) reported the AEFIs affected daily activities. The AEFIs generally spontaneously resolved within 24 h of onset. There were two vaccine-unrelated SAEs. Of 294 women with complete follow-up, 279 (95%) had term deliveries, 12 (4%) had preterm deliveries, and 3 (1%) had miscarriage or stillbirth. CONCLUSION: In our cohort, AEFIs with influenza vaccine occurred with similar frequency to those reported among healthy adults in other studies, and were generally mild and self-limited. No influenza vaccine-associated SAEs were identified.

The Pregnancy and Influenza Multinational Epidemiologic (PRIME) study: a prospective cohort study of the impact of influenza during pregnancy among women in middle-income countries.

BACKGROUND: The World Health Organization identifies pregnant women as at high-risk for severe influenza, but influenza vaccines are underutilized among pregnant women. Data on influenza burden during pregnancy are largely limited to high-income countries and data on the impact of influenza on birth and perinatal outcomes are scarce. METHODS/DESIGN: This prospective, longitudinal cohort study of pregnant women in middle-income countries is designed to address three primary objectives: 1) to evaluate the effect of laboratory-confirmed influenza during pregnancy on pregnancy and perinatal outcomes; 2) to estimate the incidences of all-cause acute respiratory illness and laboratory-confirmed influenza during pregnancy; and 3) to examine the clinical spectrum of illness associated with influenza viruses. Through a multi-country network approach, three sites aim to enroll cohorts of 1500-3000 pregnant women just before local influenza seasons. Women aged ≥ 18 years with expected delivery dates ≥ 8 weeks after the start of the influenza season are eligible. Women are followed throughout pregnancy through twice weekly surveillance for influenza symptoms (≥ 1 of myalgia, cough, runny nose, sore throat, or difficulty breathing) and have mid-turbinate nasal swabs collected for influenza virus testing during illness episodes. Primary outcomes include relative risk of preterm birth and mean birth weight among term singleton infants of women with and without reverse transcription polymerase chain reaction-confirmed influenza during pregnancy. Gestational age is determined by ultrasound at < 28 weeks gestation and birth weight is measured by digital scales using standardized methods. Sites are primarily urban in Bangkok, Thailand; Lima, Peru; and Nagpur, India. All sites recruit from antenatal clinics at referral hospitals and conduct surveillance using telephone calls, messaging applications, or home visits. Nasal swabs are self-collected by participants in Thailand and by study staff in Peru and India. During the first year (2017), sites enrolled participants during March-May in Peru and May-July in India and Thailand; 4779 women were enrolled. DISCUSSION: This study aims to generate evidence of the impact of influenza during pregnancy to inform decisions by Ministries of Health, healthcare providers, and pregnant women in middle-income countries about the value of influenza vaccination during pregnancy.

The role of asymptomatic infections in influenza transmission: what do we really know.

Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps.

Influenza-Like Symptom Incidence, Illness-Associated Expenses, and Economic Impact Among Healthcare Personnel in Thailand: A Prospective Observational Cohort Study (2020-2021).

OBJECTIVES: We estimated influenza-like symptom (ILS) incidence among healthcare personnel (HCP) in four hospitals and the economic impact due to ILS in the Thai HCP population during July 2020-June 2021 (Thailand's expected 2020 influenza season), which also coincided with the novel coronavirus disease 2019 pandemic. METHODS: We followed HCP, in a prospective observational cohort, weekly for ≥1 of: muscle pain, cough, runny nose/nasal congestion, sore throat, or difficulty breathing. We fitted population-averaged Poisson regression models to identify factors associated with acquiring ILS and to calculate ILS incidence. We applied epidemiologic parameters to Thailand's HCP population (227 349 persons) to estimate economic impact. RESULTS: Of 2184 participants, adjusted all-cause ILS incidence was 6.1 episodes per 100 person-years (95% confidence interval 3.4-10.9). Among Thailand's HCP population, 13 909 ILS episodes were estimated to occur annually and would result in US$235 135 economic loss. Controlling for study site and calendar month, factors associated with acquiring ≥1 ILS versus no ILS included being female, having asthma, and using personal protective equipment 'frequently, but not always'. CONCLUSIONS: All-cause ILS resulted in considerable economic loss among Thai HCP workforce. These findings underscore the importance of public health interventions to reduce the risk of acquiring ILS.

Changes in Personal Protective Equipment Usage Among Healthcare Personnel From the Beginning of Pandemic to Intra-COVID-19 Pandemic in Thailand.

OBJECTIVES: Personal protective equipment (PPE) use is associated with reduced risk of SARS-CoV-2 infection among healthcare personnel (HCP). There are limited data on the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on the PPE use of HCP. We describe the changes in PPE use from just before the widespread of community outbreaks ('pre-pandemic') to intra-pandemic time points, and examine factors associated with not changing in PPE use behavior among HCP in four Thai hospitals. METHODS: We performed a retrospective cohort evaluation using two-time points: (i) February-March 2020 (pre-pandemic period); and (ii) January-March 2021 (intra-pandemic period). Self-reported frequency of appropriate PPE use was measured by a Likert scale. We used multivariable logistic regression to identify factors associated with no increase in self-reported PPE use. RESULTS: Of 343 HCP, the proportion of participants reporting 'always' using PPE rose from 66% during the pre-pandemic period to 80% during the pandemic. Factors associated with HCP who did not increase in PPE use included having high baseline reported PPE, being a non-registered HCP (e.g. nurse assistants, dental assistants, porters), being male, and having a low perceived risk of becoming infected with any respiratory virus while working in the hospital. CONCLUSION: PPE education, training, and risk communication content should target all cadres of HCP, regardless of registered/non-registered status, with a focus on behavior change for improved prevention and control of SARS-CoV-2 and other respiratory viruses in healthcare settings.

Anti-SARS-CoV-2 IgG antibody levels among Thai healthcare providers receiving homologous and heterologous COVID-19 vaccination regimens.

BACKGROUND: We examined SARS-CoV-2 anti-spike 1 IgG antibody levels following COVID-19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer-BioNTech [PZ]) among Thai healthcare providers. METHODS: Blood specimens were tested using enzyme-linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ + 1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV + 1AZ, 2SV + 1PZ). Differences in antibody levels were assessed using Kruskal-Wallis statistic, Mann-Whitney test, or Wilcoxon matched-pairs signed-rank test. Antibody kinetics were predicted using fractional polynomial regression. RESULTS: The 563 participants had median age of 39 years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23 days in both 1AZ and 2SV vaccinees and dropped below assay's cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55 days among 1AZ vaccinees compared with 117 days among 2SV vaccinees. 1AZ + 1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1-4 weeks post vaccination. 2SV + 1PZ vaccinees had significantly higher antibody levels than 2SV + 1AZ vaccinees 4 weeks post vaccination (3423 vs. 2105 BAU/ml; p-value < 0.01), and during weeks 5-8 (3656 vs. 1072 BAU/ml; p-value < 0.01). Antibodies peaked at 12-15 days in both 2SV + 1PZ and 2SV + 1AZ vaccinees, but those of 2SV + 1AZ declined more rapidly and dropped below assay's cutoff in 228 days while those of 2SV + 1PZ remained detectable. CONCLUSIONS: 1AZ + 1PZ, 2SV + 1AZ, and 2SV + 1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti-S1 IgG antibodies for possible protection against SARS-CoV-2 infection.

Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.

BACKGROUND: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. METHODS AND FINDINGS: We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). CONCLUSIONS: Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.

Influenza-Associated Medical Visits Prevented by Influenza Vaccination in Young Children in Thailand, 2012-2014.

Despite recommendations, few children aged 6-35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012-2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years.

Laboratory evaluation of two point-of-care detection systems for early and accurate detection of influenza viruses in the Lao People's Democratic Republic.

BACKGROUND: We evaluated molecular-based point-of-care influenza virus detection systems in a laboratory prior to a field evaluation of on-site specimen testing. METHODS: The performance characteristics of 1) insulated isothermal polymerase chain reaction (PCR) on a POCKIT™ device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini™ device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96™ real-time detection system was used as a gold standard for comparison. RESULTS: Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT™ only correctly identified influenza A (M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini™ had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT™ was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini™ had mixed results depending on the types and subtypes of influenza viruses. CONCLUSIONS: The performance of the two systems in a laboratory is promising and supports further evaluation in field settings.

Sero-surveillance for SARS-CoV-2 infection among healthcare providers in four hospitals in Thailand one year after the first community outbreak.

BACKGROUND: Thailand was the first country outside China to report SARS-CoV-2 infected cases. Since the detection of the first imported case on January 12th, 2020 to the time this report was written, Thailand experienced two waves of community outbreaks (March-April 2020 and December 2020-March 2021). We examined prevalence of SARS-CoV-2 seropositivity among healthcare providers (HCPs) in four hospitals approximately one year after SARS-CoV-2 first detected in Thailand. By March 2021, these hospitals have treated a total of 709 coronavirus disease 2019 (COVID-19) patients. METHODS: Blood specimens, collected from COVID-19 unvaccinated HCPs during January-March 2021, were tested for the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies to nucleocapsid (IgG-nucleocapsid) and spike (IgG-spike) proteins using Euroimmune® enzyme-linked immunosorbent assays. RESULTS: Of 600 HCPs enrolled, 1 (0.2%) tested positive for the SARS-CoV-2 IgG-spike antibodies, but not the IgG-nucleocapsid. CONCLUSION: The presence of SARS-CoV-2 IgG antibodies was rare in this sample of HCPs, suggesting that this population remains susceptible to SARS-CoV-2 infection.

Knowledge, attitude/perception, and practice related to seasonal influenza vaccination among caregivers of young Thai children: A cross-sectional study.

BACKGROUND: Seasonal influenza vaccination uptake among young children in Thailand is low despite national recommendation for vaccination. We implemented a knowledge, attitude/perception, and practice survey to understand determinants of influenza vaccination in children aged six months to two years. METHODS: Using a cross-sectional design, we interviewed caregivers of 700 children in seven hospitals using a structured questionnaire to collect information on caregivers' and children's demographic characteristics, and caregivers' knowledge of influenza illness and national vaccine recommendation, attitude/perception toward influenza vaccine, and information sources. We verified children's influenza vaccination status against medical records (vaccinated vs. unvaccinated). Logistic regression was used to examine factors independently associated with children receiving influenza vaccination in the 2018 season using the dataset restricted to only children's parents. Variables associated with vaccination at p-value ≤0.20 were included in subsequent multivariable logistic models. Significant independent determinants of children's influenza vaccination and collinearity of covariates were assessed. The final model was constructed using a stepwise backward elimination approach with variables significant at p-value <0.05 retained in the model. RESULTS: During August 2018-February 2019, 700 children's caregivers completed the questionnaire; 61 (9%) were caregivers of vaccinated children. Caregivers of the vaccinated children were statistically more likely to have higher education (61% vs. 38%; p-value<0.01) and to know of influenza illness (93% vs. 76%; p-value = 0.03) than those of the unvaccinated group. Factors associated with children receiving influenza vaccination were identifying healthcare providers as a primary source of information about influenza illness for parents (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.3-6.0), parents' strongly agreeing with the national recommendation for influenza vaccination in young children (aOR, 2.9; 95% CI, 1.5-5.9), using health insurance provided by the government or parent's employer for children's doctor visits (aOR, 2.6; 95% CI, 1.1-6.6), and the children's history of receiving influenza vaccination in the 2017 season or earlier (aOR, 3.2; 95% CI, 1.4-7.8). CONCLUSION: The majority of caregivers of children in this study had knowledge of influenza illness and influenza vaccine. Caregivers reported various sources of information regarding influenza illness and the vaccine, but healthcare providers remained the most trusted source. Children's history of influenza vaccination in prior season(s) was the strongest determinant of children being vaccinated for influenza in the current season.

Cost-effectiveness of seasonal influenza vaccination in pregnant women, healthcare workers and adults >= 60 years of age in Lao People's Democratic Republic.

BACKGROUND: Pregnant women, healthcare workers (HW), and adults >= 60 years have shown an increased vulnerability to seasonal influenza virus infections and/or complications. In 2012, the Lao People's Democratic Republic (Lao PDR) initiated a national influenza vaccination program for these target groups. A cost-effectiveness evaluation of this program was undertaken to inform program sustainability. METHODS: We designed a decision-analytical model and collected influenza-related medical resource utilization and cost data, including indirect costs. Model inputs were obtained from medical record abstraction, interviews of patients and staff at hospitals in the national influenza sentinel surveillance system and/or from literature reviews. We compared the annual disease and economic impact of influenza illnesses in each of the target groups in Lao PDR under scenarios of no vaccination and vaccination, and then estimated the cost-effectiveness of the vaccination program. We performed sensitivity analyses to identify influential variables. RESULTS: Overall, the vaccination of pregnant women, HWs, and adults >= 60 years could annually save 11,474 doctor visits, 1,961 days of hospitalizations, 43,027 days of work, and 1,416 life-years due to laboratory-confirmed influenza illness. After comparing the total vaccination program costs of 23.4 billion Kip, to the 18.4 billion Kip saved through vaccination, we estimated the vaccination program to incur a net cost of five billion Kip (599,391 USD) annually. The incremental cost per life-year saved (ICER) was 44 million Kip (5,295 USD) and 6.9 million Kip (825 USD) for pregnant women and adults >= 60 years, respectively. However, vaccinating HWs provided societal cost-savings, returning 2.88 Kip for every single Kip invested. Influenza vaccine effectiveness, attack rate and illness duration were the most influential variables to the model. CONCLUSION: Providing influenza vaccination to HWs in Lao PDR is cost-saving while vaccinating pregnant women and adults >= 60 is cost-effective and highly cost-effective, respectively, per WHO standards.

Comparison of influenza antibody titers among women who were vaccinated in the 2nd and the 3rd trimesters of pregnancy.

BACKGROUND: We compared cord blood antibody titers in unvaccinated pregnant women to those vaccinated with seasonal influenza vaccine during the 2nd and the 3rd trimesters. METHODS: Pregnant women had cord blood collected at delivery for hemagglutination inhibition assay against vaccine reference viruses: A/California/07/2009 (H1N1)pdm09, A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 (Yamagata lineage). Geometric mean titer (GMT) ratios were calculated comparing vaccinated versus unvaccinated pregnant women, and women vaccinated in the 2nd and the 3rd trimesters. Proportions of women achieving defined titers were compared using the χ2 test. RESULTS: Of 307 women, 190 (62%) were unvaccinated. Fifty and 67 were vaccinated during the 2nd and the 3rd trimesters, respectively. Median enrollment age was 29 years (interquartile range 24-34). Sixteen (5%) women had pre-existing conditions, but none were immunocompromised. GMT ratios comparing vaccinated and unvaccinated women were 5.90 (95% confidence interval [CI] 5.06-6.96) for influenza A/California, 5.39 (95% CI 4.18-6.08) for influenza A/Switzerland, and 5.05 (95% CI 4.43-5.85) for influenza B/Phuket. Similarly, the GMT ratios comparing the 3rd and the 2nd trimester vaccinated women were 2.90 (95% CI 2.54-3.39), 2.82 (95% CI 2.56-3.13), and 2.83 (95% CI 2.56-3.14), respectively. The proportions of women with defined titers for the three vaccine reference viruses did not differ between 2nd and 3rd trimester vaccinated women (titers ≥40: 68-92% versus 70-93%; ≥110: 32% versus 33-63%; and ≥330: 4-10% versus 3-21%). CONCLUSIONS: Pregnant women vaccinated against influenza had more placental transfer of influenza antibodies to their infants than unvaccinated women. Placental transfer of antibodies was higher among those vaccinated in the 3rd trimester than in the 2nd trimester. There was no difference in the proportions of women achieving antibody titers corresponding to protection against influenza in children. Findings support the current World Health Organization's recommendation that pregnant women may be vaccinated in either 2nd or 3rd trimester of pregnancy.

What do pregnant women think about influenza disease and vaccination practices in selected countries.

Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries.Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression.Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value<0.01). Despite significant differences in sociodemographic characteristics in the three populations, most participants across sites who were aware of influenza prior to study enrollment believe they and their infants are at risk of influenza and related complications and believe influenza vaccination is safe and effective. Half of women in Lima had verified receipt of influenza vaccine compared to <5% in Bangkok and Nagpur (p < .05). For further analysis conducted among women in Lima only, household income above the poverty line (aOR: 1.38; 95%CI: 1.01, 1.88), having 8+ antenatal visits, compared to 0-4 (aOR: 2.41; 95%CI: 1.39, 2.87, respectively), having 0 children, compared to 2+ (aOR: 1.96; 95%CIs: 1.23, 3.12), and vaccination recommended by a health-care provider (aOR: 8.25; 95%CI: 6.11, 11.14) were strongly associated with receipt of influenza vaccine during pregnancy.Conclusions: Our findings identify opportunities for targeted interventions to improve influenza vaccine uptake among pregnant women in these settings.

Incidence of influenza during pregnancy and association with pregnancy and perinatal outcomes in three middle-income countries: a multisite prospective longitudinal cohort study.

BACKGROUND: Influenza vaccination during pregnancy prevents influenza among women and their infants but remains underused among pregnant women. We aimed to quantify the risk of antenatal influenza and examine its association with perinatal outcomes. METHODS: We did a prospective cohort study in pregnant women in India, Peru, and Thailand. Before the 2017 and 2018 influenza seasons, we enrolled pregnant women aged 18 years or older with expected delivery dates 8 weeks or more after the season started. We contacted women twice weekly until the end of pregnancy to identify illnesses with symptoms of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing and collected mid-turbinate nasal swabs from symptomatic women for influenza real-time RT-PCR testing. We assessed the association of antenatal influenza with preterm birth, late pregnancy loss (≥13 weeks gestation), small for gestational age (SGA), and birthweight of term singleton infants using Cox proportional hazards models or generalised linear models to adjust for potential confounders. FINDINGS: Between March 13, 2017, and Aug 3, 2018, we enrolled 11 277 women with a median age of 26 years (IQR 23-31) and gestational age of 19 weeks (14-24). 1474 (13%) received influenza vaccines. 310 participants (3%) had influenza (270 [87%] influenza A and 40 [13%] influenza B). Influenza incidences weighted by the population of women of childbearing age in each study country were 88·7 per 10 000 pregnant woman-months (95% CI 68·6 to 114·8) during the 2017 season and 69·6 per 10 000 pregnant woman-months (53·8 to 90·2) during the 2018 season. Antenatal influenza was not associated with preterm birth (adjusted hazard ratio [aHR] 1·4, 95% CI 0·9 to 2·0; p=0·096) or having an SGA infant (adjusted relative risk 1·0, 95% CI 0·8 to 1·3, p=0·97), but was associated with late pregnancy loss (aHR 10·7, 95% CI 4·3 to 27·0; p<0·0001) and reduction in mean birthweight of term, singleton infants (-55·3 g, 95% CI -109·3 to -1·4; p=0·0445). INTERPRETATION: Women had a 0·7-0·9% risk of influenza per month of pregnancy during the influenza season, and antenatal influenza was associated with increased risk for some adverse pregnancy outcomes. These findings support the added value of antenatal influenza vaccination to improve perinatal outcomes. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Thai, Hindi, Marathi and Spanish translations of the abstract see Supplementary Materials section.

HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study.

BACKGROUND: In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment. METHODS: We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death. RESULTS: Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07-0.36), fluconazole use (HR 0.34; CI 0.18-0.64), and co-trimoxazole use (HR 0.41; CI 0.20-0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death. CONCLUSION: Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.