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 ≥ 50(th) 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.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

BACKGROUND: We explored whether hospital-based surveillance is useful in detecting severe acute respiratory infection (SARI) clusters and how often these events result in outbreak investigation and community mitigation. METHODS: During May 2009-December 2020, physicians at 14 sentinel hospitals prospectively identified SARI clusters (i.e., ≥2 SARI cases who developed symptoms ≤10 days of each other and lived <30 min walk or <3 km from each other). Oropharyngeal and nasopharyngeal swabs were tested for influenza and other respiratory viruses by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We describe the demographic of persons within clusters, laboratory results, and outbreak investigations. RESULTS: Field staff identified 464 clusters comprising 1427 SARI cases (range 0-13 clusters per month). Sixty percent of clusters had three, 23% had two, and 17% had ≥4 cases. Their median age was 2 years (inter-quartile range [IQR] 0.4-25) and 63% were male. Laboratory results were available for the 464 clusters with a median of 9 days (IQR = 6-13 days) after cluster identification. Less than one in five clusters had cases that tested positive for the same virus: respiratory syncytial virus (RSV) in 58 (13%), influenza viruses in 24 (5%), human metapneumovirus (HMPV) in five (1%), human parainfluenza virus (HPIV) in three (0.6%), adenovirus in two (0.4%). While 102/464 (22%) had poultry exposure, none tested positive for influenza A (H5N1) or A (H7N9). None of the 464 clusters led to field deployments for outbreak response. CONCLUSIONS: For 11 years, none of the hundreds of identified clusters led to an emergency response. The value of this event-based surveillance might be improved by seeking larger clusters, with stronger epidemiologic ties or decedents.

Background We compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women.Methods During 1st June – 30th September 2018, four groups of cohort participants - vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels.Results A total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs were similar for influenza A(H1N1), A(H3N2), and B vaccine strains among all four groups (all p-values &gt;0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values &lt;0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Pregnant women had similar antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) to non-pregnant women for all three strains of IIV3 (all p&gt;0.05).Conclusions The 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThai Clinical Trials Registry ID: TCTR20201014004Funding StatementThis study was partially supported by the Nakhon Phanom Provincial Hospital Foundation (ref no. NP 0032.202.3/7) secured by KP and SN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study protocol was reviewed and approved by the Ethical Review Committee of Thammasat University (Ref no. MTU-EC-ES-4-217/60). Approval of local ethics committee of Nakhon Phanom Hospital (No. NP-EC11-No.4/2560) was also received prior to the data collection.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll relevant data are within the paper and the supporting files.

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.

BACKGROUND: Using country-specific surveillance data to describe influenza epidemic activity could inform decisions on the timing of influenza vaccination. We analysed surveillance data from African countries to characterise the timing of seasonal influenza epidemics to inform national vaccination strategies. METHODS: We used publicly available sentinel data from African countries reporting to the WHO Global Influenza Surveillance and Response FluNet platform that had 3-10 years of data collected during 2010-19. We calculated a 3-week moving proportion of samples positive for influenza virus and assessed epidemic timing using an aggregate average method. The start and end of each epidemic were defined as the first week when the proportion of positive samples exceeded or went below the annual mean, respectively, for at least 3 consecutive weeks. We categorised countries into five epidemic patterns: northern hemisphere-dominant, with epidemics occurring in October-March; southern hemisphere-dominant, with epidemics occurring in April-September; primarily northern hemisphere with some epidemic activity in southern hemisphere months; primarily southern hemisphere with some epidemic activity in northern hemisphere months; and year-round influenza transmission without a discernible northern hemisphere or southern hemisphere predominance (no clear pattern). FINDINGS: Of the 34 countries reporting data to FluNet, 25 had at least 3 years of data, representing 46% of the countries in Africa and 89% of Africa's population. Study countries reported RT-PCR respiratory virus results for a total of 503 609 specimens (median 12 971 [IQR 9607-20 960] per country-year), of which 74 001 (15%; median 2078 [IQR 1087-3008] per country-year) were positive for influenza viruses. 248 epidemics occurred across 236 country-years of data (median 10 [range 7-10] per country). Six (24%) countries had a northern hemisphere pattern (Algeria, Burkina Faso, Egypt, Morocco, Niger, and Tunisia). Eight (32%) had a primarily northern hemisphere pattern with some southern hemisphere epidemics (Cameroon, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Tanzania, and Togo). Three (12%) had a primarily southern hemisphere pattern with some northern hemisphere epidemics (Ghana, Kenya, and Uganda). Three (12%) had a southern hemisphere pattern (Central African Republic, South Africa, and Zambia). Five (20%) had no clear pattern (Côte d'Ivoire, DR Congo, Madagascar, Mauritius, and Rwanda). INTERPRETATION: Most countries had identifiable influenza epidemic periods that could be used to inform authorities of non-seasonal and seasonal influenza activity, guide vaccine timing, and promote timely interventions. FUNDING: None. TRANSLATIONS: For the Berber, Luganda, Xhosa, Chewa, Yoruba, Igbo, Hausa and Afan Oromo translations of the abstract see Supplementary Materials section.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

BACKGROUND: We measured the immunogenicity of seasonal trivalent inactivated influenza vaccines (IIV3) among older Thai adults and the effect of one-year prior vaccination status on immune responses. METHOD: Adults aged ≥65 years (n = 370) were vaccinated with Southern Hemisphere IIV3 in 2015. Hemagglutination inhibition assays were performed using goose red blood cells on sera collected from the participants at baseline and after 1, 6, and 12 months of vaccination. Prior year vaccination (in 2014) was verified with the national health security office database. We analyzed the associations between prior vaccination and geometric mean titers (GMT) at each time point using generalized linear regression on logged transformed titers, and seroprotection and seroconversion using Log-binomial regression. RESULTS: At baseline, previously vaccinated participants (n = 203) had a significantly higher GMT and seroprotection against all three influenza strains than those previously unvaccinated (n = 167) (all p-values <0.001). Seroprotection rates were similar after one month in both groups for A(H1N1)pdm09 (adjusted risk ratio [aRR] 1.10, 95% CI 0.97-1.25), and A(H3N2) (aRR 1.08, 95% CI 0.87-1.33), but higher in previously vaccinated persons for B (aRR 1.20, 95% CI 1.08-1.32). At 12 months, 50% or more had seroprotection in previously vaccinated group with no difference between previously vaccinated or unvaccinated persons. Seroconversion was lower in the previously vaccinated group for A(H1N1)pdm09 (aRR 0.62, 95% CI 0.43-0.89), but did not differ between the two groups for A(H3N2) (aRR 0.94, 95% CI 0.69-1.28) and B (aRR 0.85, 95% CI 0.60-1.20). CONCLUSION: Influenza vaccination elicited good humoral response in older Thai adults. While seroconversion seemed attenuated in persons previously vaccinated for influenza A(H1N1)pdm09 (the only vaccine strain not to change), this was not apparent for influenza A(H3N2) and B, and prior vaccination was not associated with any inhibition in seroprotection.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

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.

Background: We examined the characteristics of healthcare providers’ (HCPs) encounters, and the frequency of worker absenteeism/presenteeism, among HCPs in inpatient wards at a tertiary-level public hospital in Bangkok, Thailand. The wards were stratified by risk of respiratory virus transmission: low-risk (Surgery, Rehabilitation, Orthopedic, and Obstetrics and Gynecology) and high-risk (Medicine, Pediatric, Emergency, and Ear, Nose, and Throat). Methods: Observers followed HCPs throughout one self-selected 8-hour work shift to record their interaction with others. An encounter was defined as a 2-way conversation with ≥3 words in the physical presence of ≥1 person at <3 feet distance; or a physical skin-to-skin touch. We administered structured questionnaires to document demographics, health and work history, past practice while ill, and recent and current acute muscle pain and/or respiratory symptoms. We collected data from time and attendance records of participants reporting illness within the past seven days. Results: From July to August 2019, 240 HCPs were enrolled and observed during 395 work shifts; 15,878 total encounters were made with a median duration of two minutes (interquartile range, 1–3). Number of contacts ranged from 25 to 49 encounters/8 h in the low-risk wards and 40 to 66 encounters/8 h in the high-risk wards. Physicians working during the 8-hour evening shift in high-risk wards had the highest estimated number of contacts (66 encounters; 95% confidence interval [CI], 43–89) while nurses working during the 8-hour night shift in the low-risk wards had the lowest number of contacts (25 encounters; 95% CI, 22–28). Forty-two (11%) shifts were staffed by HCPs with acute muscle pain and/or respiratory symptom(s) at the time of interview, and 89 (23%) by HCPs who reported symptom(s) during the past seven days, for which none were absent from work. Conclusion: We observed difference in encounter patterns by ward type. About one in five work shifts were staffed by HCPs with acute muscle pain and/or respiratory symptoms who continued to work while ill. These findings have implications for preventing infectious disease transmission and the policy around sick leave in healthcare settings. © 2022

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 39years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23days in both 1AZ and 2SV vaccinees and dropped below assay's cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55days among 1AZ vaccinees compared with 117days among 2SV vaccinees. 1AZ+1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1-4weeks post vaccination. 2SV+1PZ vaccinees had significantly higher antibody levels than 2SV+1AZ vaccinees 4weeks 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 12-15days in both 2SV+1PZ and 2SV+1AZ vaccinees, but those of 2SV+1AZ declined more rapidly and dropped below assay's cutoff in 228days 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.

BACKGROUND: Low global influenza circulation was reported during the coronavirus-19 pandemic. We explored relationships between non-pharmaceutical interventions (NPIs) and influenza in tropical Asian countries. METHODS: Using World Health Organization (WHO) surveillance data from 2015 to 2019 and the WHO shiny app, we constructed expected seasonal influenza epidemic curves from March 2020 to June 2021 and compared the timing, and average percent positivity with observed data. We used multivariate regression to test associations between ordinal NPI data (from the Oxford Stringency Index) 4 weeks before the expected 2020/21 epidemics and present adjusted incidence rate ratio (IRR) or relative proportion ratio (RPR) and 95% confidence intervals (CI). RESULTS: Data from nine countries predicted 18 seasonal epidemics; seven were observed. Five started 6-24 weeks later, and all were 4-21 weeks shorter than expected. Five epidemics had lower maximum peak values (percent positivity), and all but one had lower average percent positivity than expected. All countries implemented NPIs. Each increased level of school closure reduced risk of an epidemic by 43% (IRR = 0.57, CI: 0.34, 0.95). Each increased level of canceling public events reduced the average percent positivity across the season by 44% (RPR = 0.56, CI: 0.39, 0.82) and each increased level in restricting internal movements reduced it by 41% (RPR = 0.59, CI: 0.36, 0.96). Other NPIs were not associated with changes. CONCLUSIONS: Among nine countries, the 2020/21 seasonal epidemics were delayed, shorter, and less intense than expected. Although layered NPIs were difficult to tease apart, school closings, canceling public events, and restricting internal movements before influenza circulation seemed to reduce transmission.

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.

In March 2021, Lao People's Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.

In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child's house was positive for H9N2 virus and genetically similar to the human virus.

OBJECTIVE: Estimates of the burden of influenza are needed to inform prevention and control activities for seasonal influenza, including to support the development of appropriate vaccination policies. We used sentinel surveillance data on severe acute respiratory infection (SARI) to estimate the burden of influenza-associated hospitalizations in the Lao People's Democratic Republic. METHODS: Using methods developed by the World Health Organization, we combined data from hospital logbook reviews with epidemiological and virological data from influenza surveillance from 1 January to 31 December 2016 in defined catchment areas for two sentinel sites (Champasack and Luang Prabang provincial hospitals) to derive population-based estimates of influenza-associated SARI hospitalization rates. Hospitalization rates by age group were then applied to national age-specific population estimates using 2015 census data. RESULTS: We estimated the overall influenza-associated SARI hospitalization rate to be 48/100 000 population (95% confidence interval [CI]: 44-51) or 3097 admissions (95% CI: 2881-3313). SARI hospitalization rates were estimated to be as low as 40/100 000 population (95% CI: 37-43) and as high as 92/100 000 population (95% CI: 87-98) after accounting for SARI patient underascertainment in hospital logbooks. Influenza-associated SARI hospitalization rates were highest in children aged < 5 years (219; 95% CI: 198-241) and persons aged (3) 65 years (106; 95% CI: 91-121). DISCUSSION: Our findings have identified age groups at higher risk for influenza-associated SARI hospitalization, which will support policy decisions for influenza prevention and control strategies, including for vaccination. Further work is needed to estimate the burdens of outpatient influenza and influenza in specific high-risk subpopulations.

INTRODUCTION: During the 2019 novel coronavirus infectious disease (COVID-19) pandemic in 2020, limited data from several countries suggested reduced seasonal influenza viruses' circulation. This was due to community mitigation measures implemented to control the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used sentinel surveillance data to identify changes in the 2020 influenza season compared with previous seasons in Bangladesh. METHODS: We used hospital-based influenza surveillance (HBIS) data of Bangladesh that are generated year-round and are population-representative severe acute respiratory infection (SARI) data for all age groups from seven public and two private tertiary care level hospitals data from 2016 to 2019. We applied the moving epidemic method (MEM) by using R language (v4.0.3), and MEM web applications (v2.14) on influenza-positive rates of SARI cases collected weekly to estimate an average seasonal influenza curve and establish epidemic thresholds. RESULTS: The 2016-2019 average season started on epi week 18 (95% CI: 15-25) and lasted 12.5 weeks (95% CI: 12-14 weeks) until week 30.5. The 2020 influenza season started on epi week 36 and ended at epi week 41, lasting for only five weeks. Therefore, influenza epidemic started 18 weeks later, was 7.5 weeks shorter, and was less intense than the average epidemic of the four previous years. The 2020 influenza season started on the same week when COVID-19 control measures were halted, and 13 weeks after the measures were relaxed. CONCLUSION: Our findings suggest that seasonal influenza circulation in Bangladesh was delayed and less intense in 2020 than in previous years. Community mitigation measures may have contributed to this reduction of seasonal influenza transmission. These findings contribute to a limited but growing body of evidence that influenza seasons were altered globally in 2020.

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.

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.

BACKGROUND: We compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women. METHODS: During 1st June- 30th September 2018, four groups of cohort participants-vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels. RESULTS: A total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs for influenza A(H1N1), A(H3N2), and B vaccine strains were not significantly different among all four groups (all p-values >0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values <0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) were not significantly different between pregnant and non-pregnant women for all three strains of IIV3 (all p>0.05). CONCLUSIONS: The 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.

BACKGROUND: In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children <5 years hospitalized with a clinical diagnosis of respiratory disease at Kenya's largest referral hospital. METHODS: We collected respiratory and other tissues postmortem to examine pathologic processes using histology, molecular and immunohistochemistry assays. Nasopharyngeal, trachea, bronchi and lung specimens were tested using 21-target respiratory pathogen real-time reverse transcription polymerase chain reaction assays deployed on Taqman Array Cards. Expert panels reviewed all findings to determine causes of death and associated pathogens. RESULTS: From 2014 to 2015, we investigated 64 pediatric deaths (median age 7 months). Pneumonia was determined as cause of death in 70% (42/52) of cases where death was associated with an infectious disease process. The main etiologies of pneumonia deaths were respiratory syncytial virus (RSV) (n = 7, 19%), Pneumocystis jirovecii (n = 7, 19%), influenza A (n = 5, 14%) and Streptococcus pneumoniae (n = 5, 14%)-10% of cases had multi-pathogen involvement. Among the other 10 deaths associated with a nonpneumonia infectious process, 4 did not have an etiology assigned, the others were associated with miliary tuberculosis (2), cerebral thrombosis due to HIV (1), Enterobacteriaceae (1), rotavirus (1), and 1 case of respiratory infection with severe hypokalemia associated with RSV. CONCLUSIONS: In spite of well-established vaccination programs in Kenya, some deaths were still vaccine preventable. Accelerated development of RSV monoclonal antibodies and vaccines, introduction of seasonal influenza vaccination, and maintenance or improved uptake of existing vaccines can contribute to further reductions in childhood mortality.

BACKGROUND: Adults with cardiopulmonary conditions may be at increased risk of influenza and respiratory syncytial virus (RSV) infection, but it is not well-established and few data are available from middle-income countries. METHODS: Using data from a prospective cohort study of influenza vaccine effectiveness, we estimated and compared the incidences of influenza and RSV between community-dwelling Thai adults aged ≥ 65 years with and without cardiopulmonary conditions. During May 2015-May 2017, older adults in a rural province in Thailand were followed-up with weekly surveillance for acute respiratory illness (ARI), defined broadly as new onset or worsening of cough with or without fever, and hospitalized ARI. When ill, nasal self-swabs and/or nasopharyngeal swabs were collected for reverse-transcription polymerase chain reaction testing. We used Poisson regression to calculate incidence rate ratios (IRR), adjusting for age, sex, current smoking, number of hospital visits, weekly influenza activity, and influenza vaccination. RESULTS: Overall, 3220 adults with a median age of 71 years (IQR 68-76) were enrolled; 1324 (41.1%) were male; and 313 (9.7%) had ≥1 underlying cardiopulmonary condition, most commonly chronic obstructive pulmonary disease (131; 41.2%) or asthma (73; 23.3%). Participants with cardiopulmonary conditions had higher incidences of ARI, influenza, and RSV than those without (Adjusted IRR: 1.84, 95% CI 1.64-2.07; 1.86, 95% CI 1.07-3.26; 2.04, 95% CI 1.11-3.76, respectively). CONCLUSION: Older adults in rural Thailand with cardiopulmonary conditions have increased rates of ARI, influenza, and RSV infections. Our findings support efforts to ensure this population has access to influenza vaccines and other respiratory illness prevention measures.

Global influenza virus circulation declined and has been below traditional seasonal levels during the COVID‐19 pandemic. 1 , 2 , 3 After learning of increased influenza virus circulation in some tropical Asian countries, we reviewed current surveillance data to better ascertain risk for an influenza resurgence during the 2020‐2021 Northern Hemisphere influenza season and subsequent seasons during the COVID‐19 pandemic.

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.

BACKGROUND: We assessed performance of participant-collected mid-turbinate nasal swabs compared to study staff-collected mid-turbinate 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 (ARI) self-collected mid-turbinate nasal swabs at homes for influenza viruses, RSV, and hMPV real-time RT-PCR testing while the study nurse collected a second mid-turbinate 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 two days and to staff-collected swabs was also two days. The median time difference between the two swabs was two 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 mid-turbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

BACKGROUND: We evaluated molecular-based point-of-care influenza detection systems in a laboratory prior to the field evaluations of on-site specimen testing. METHODS: Performance of 1) insulated isothermal PCR on the POCKIT(TM) 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(TM) Real-time Detection System was used as a gold standard for comparisons. RESULTS: Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT(TM) 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(TM) 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.

BACKGROUND: Coinciding with the COVID-19 pandemic, global influenza virus circulation decreased, possibly due to widespread community mitigation measures. Cambodia eased some COVID-19 mitigation measures in June and July 2020. On Aug 20th a cluster of respiratory illnesses among residents of a pagoda included persons that had tested positive for influenza A, and none that were positive for SARS-CoV-2. METHODS: On Aug 25, a response team deployed. Persons with influenza-like illness (ILI) were asked questions on demographics, illness, personal prevention measures, and residential arrangements. Respiratory swabs were tested for influenza and SARS-Cov-2 by RT-PCR; viruses were sequenced. Sentinel surveillance data were analyzed to assess recent trends in influenza circulation in the community. RESULTS: Influenza A(H3N2) viruses were identified in sentinel surveillance in Cambodia in July 2020, prior to the reported pagoda outbreak. Among the 362 pagoda residents, 73(20.2%) ILI cases were identified; 40 were tested with 33/40 (82.5%) confirmed positive for influenza A(H3N2). All 40 were negative for SARS-CoV-2. Among 73 residents with ILI, none were vaccinated against influenza, 47 (64%) clustered in 3 of 8 sleeping quarters; 20 (27%) reported often wearing a mask; 27 (36%) reported often washing hands; and 11 (15%) reported practicing social distancing. All viruses clustered within clade 3c2.A1 close to strains circulating in Australia in 2020. CONCLUSIONS: Circulation of influenza viruses began in the community following a relaxing of national COVID-19 mitigation measures, and prior to this outbreak in a pagoda with limited social distancing. Continued surveillance and influenza vaccination remain needed to limit the impact of influenza globally.

BACKGROUND: We compared cord blood antibody titers in unvaccinated pregnant women to those vaccinated with seasonal influenza vaccine during the 2(nd) and the 3(rd) 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 2(nd) and the 3(rd) trimesters. Proportions of women achieving defined titers were compared using the χ(2) test. RESULTS: Of 307 women, 190 (62%) were unvaccinated. Fifty and 67 were vaccinated during the 2(nd) and the 3(rd) 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 3(rd) and the 2(nd) 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 2(nd) and 3(rd) 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 3(rd) trimester than in the 2(nd) 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 2(nd) or 3(rd) trimester of pregnancy.

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.