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Background: A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as these condary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies onherd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results: We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently.Conclusions: There were several factors that made the task of data management doable and efficient. First, a pretrial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed [ABSTRACT FROM AUTHOR]

Background: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. Methods: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. Results: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%-3.1%) to 45.2% (95% BCI: 36.5%-53.9%) and 0% to 23.0% (95% BCI: 16.4%-31.2%) from village-to-village, respectively. Using the 0-7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17-40-year old (OR = 8.76; 95% BCI: 6.03-12.47) and 11-16-year old (OR = 8.59; 95% BCI: 4.74-14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50-3.21). Discussion: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants. [ABSTRACT FROM AUTHOR]

Background: The transmission of soil-transmitted helminths (STHs) is associated with poverty, poor hygiene behaviour, lack of clean water and inadequate waste disposal and sanitation. Periodic administration of benzimidazole drugs is the mainstay for global STH control but it does not prevent re-infection, and is unlikely to interrupt transmission as a stand-alone intervention. Findings: We reported recently on the development and successful testing in Hunan province, PR China, of a health education package to prevent STH infections in Han Chinese primary school students. We have recently commenced a new trial of the package in the ethnically diverse Xishuangbanna autonomous prefecture in Yunnan province and the approach is also being tested in West Africa, with further expansion into the Philippines in 2015. Conclusions: The work in China illustrates well the direct impact that health education can have in improving knowledge and awareness, and in changing hygiene behaviour. Further, it can provide insight into the public health outcomes of a multi-component integrated control program, where health education prevents re-infection and periodic drug treatment reduces prevalence and morbidity. [ABSTRACT FROM AUTHOR]

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infection (LRTI) is an important cause of morbidity and mortality in infants and young children. However, the etiological role of viruses and the timing of developing LRTI are not well defined.Methods: We analyzed the data of a prospective cohort study in the Philippines as a birth cohort. We detected LRTI among children who visited healthcare facilities with respiratory symptom, and collected nasopharyngeal swabs for virus detection. We analyzed the incidence rates (IRs) and cumulative proportion of LRTI and severe LRTI by age group and each virus detected.Results: A total of 350 LRTI episodes were observed from 473 child-years yielded from 419 children. The IRs of LRTI were 70.8, 70.7, and 80.8 per 100 child-years for 0-5, 6-11, and 12-23 months of age, respectively. By 12 months of age, 45% of children developed LRTI at least once. Rhinovirus and respiratory syncytial virus were the most frequently detected viruses in all age groups. However, the IRs of influenza virus were low especially at 0-5 months of age.Conclusions: We identified various patterns of age-specific IRs of LRTI and severe LRTI for different viruses, which should be considered to establish more effective interventions including vaccinations. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide, but reports of temporal changes in the risk of transmission among close contacts has been scarce. This study aimed to examine an association between the viral load trajectory and transmission risk to develop a better control strategy for the disease spread. We conducted a household-based prospective cohort study in Biliran Province, the Philippines, and enrolled 451 participants to observe the development of acute respiratory infection. Including the cases found at the health-care facility, we analyzed the data of viral loads with symptom records obtained from 172 followed participants who had household member positive for RSV with a rapid test during an RSV outbreak in 2018–2019. We developed a model estimating a temporal change in the viral shedding from the infection and evaluated transmission dynamics. We found that most transmission events occurred within approximately 7 days of the household exposure, including potential presymptomatic transmissions. The inferred risk of infection among those younger than 5 years was 3.5 times higher than that of those older than 5 years. This finding suggested that the initial week after the household exposure is particularly important for preventing RSV spread. [ABSTRACT FROM AUTHOR]

In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12–16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863. Author summary: Children living in areas endemic to schistosomiasis typically do not present signs of acute illness during infection. It is believed that fetal exposure from a pregnant mother with infection primes the offspring and influences the child's susceptibility and immune response to infection. Praziquantel treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective, but the long-term impact on the child's immunity is not fully understood. This study enrolled 295 children at age six, who were born to mothers who participated in a randomized controlled trial of praziquantel vs placebo for S. japonicum infection during pregnancy. The children were assessed and treated for S. japonicum infection and blood was collected to measure immune response markers. We found that praziquantel treatment during pregnancy did not impact the prevalence or intensity of naturally acquired S. japonicum infection among children at age six. Among the 37 children with S. japonicum infection, immune response markers did not differ by maternal treatment group. This evidence further supports the safe use of praziquantel for pregnant women. [ABSTRACT FROM AUTHOR]

Objectives: Gold standard cause of death data is critically important to improve verbal autopsy (VA) methods in diagnosing cause of death where civil and vital registration systems are inadequate or poor. As part of a three-country research study—Improving Methods to Measure Comparable Mortality by Cause (IMMCMC) study—data were collected on clinicopathological criteria-based gold standard cause of death from hospital record reviews with matched VAs. The purpose of this data note is to make accessible a de-identified format of these gold standard VAs for interested researchers to improve the diagnostic accuracy of VA methods. Data description: The study was conducted between 2011 and 2014 in the Philippines, Bangladesh, and Papua New Guinea. Gold standard diagnoses of underlying causes of death for deaths occurring in hospital were matched to VAs conducted using a standardized VA questionnaire developed by the Population Health Metrics Consortium. 3512 deaths were collected in total, comprised of 2491 adults (12 years and older), 320 children (28 days to 12 years), and 702 neonates (0–27 days). [ABSTRACT FROM AUTHOR]

Background: Almost all countries without complete vital registration systems have data on deaths collected by hospitals. However, these data have not been widely used to estimate cause of death (COD) patterns in populations because only a non-representative fraction of people in these countries die in health facilities. Methods that can exploit hospital mortality statistics to reliably estimate community COD patterns are required to strengthen the evidence base for disease and injury control programs. We propose a method that weights hospital-certified causes by the probability of death to estimate population cause-specific mortality fractions (CSMFs).Methods: We used an established verbal autopsy instrument (VAI) to collect data from hospital catchment areas in Chandpur and Comilla Districts, Bangladesh, and Bohol province, the Philippines, between 2011 and 2014, along with demographic covariates for each death. Hospital medical certificates of cause of death (death certificates) were collected and mapped to the corresponding cause categories of the VAI. Tariff 2.0 was used to assign a COD for community deaths. Logistic regression models were created for broad causes in each country to calculate the probability of in-hospital death, given a set of covariate values. The reweighted CSMFs for deaths in the hospital catchment population, represented by each hospital death, were calculated from the corresponding regression models.Results: We collected data on 4228 adult deaths in the Philippines and 3725 deaths in Bangladesh. Short time to hospital and education were consistently associated with in-hospital death in the Philippines and absence of a disability was consistently associated with in-hospital death in Bangladesh. Non-communicable diseases (excluding stroke) and stroke were the leading causes of death in both the Philippines (33.9%, 19.1%) and Bangladesh (46.1%, 21.1%) according to the reweighted method. The reweighted method generally estimated CSMFs that fell between those derived from hospitals and those diagnosed by Tariff 2.0.Conclusions: Statistical methods can be used to derive estimates of cause-specific probability of death in-hospital for Bangladesh and the Philippines to generate population CSMFs. In regions where hospital death certification is of reasonable quality and routine verbal autopsy is not applied, these estimates could be applied to generate cost-effective and robust CSMFs for the population. [ABSTRACT FROM AUTHOR]

Abstract Objective Large-scale otoscopic and audiometric assessment of populations is difficult due to logistic impracticalities, particularly in low- and middle-income countries (LMIC). We report a novel assessment methodology based on training local field workers, advances in audiometric testing equipment and cloud-based technology. Methods Prospective observational study in Bohol, Philippines. A U.S. otolaryngologist/audiologist team trained 5 local nurses on all procedures in a didactic and hands-on process. An operating otoscope (Welch-AllynR) was used to clear cerumen and view the tympanic membrane, images of which were recorded using a video otoscope (JedMedR). Subjects underwent tympanometry and distortion product otoacoustic emission (DPOAE) (Path SentieroR), and underwent screening audiometry using noise cancelling headphones and a handheld Android device (HearScreenR). Sound-booth audiometry was reserved for failed subjects. Data were uploaded to a REDCap database. Teenage children previously enrolled in a 2000–2004 Phase 3 pneumococcal conjugate vaccine trial, were the subjects of the trainees. Results During 4 days of training, 47 Filipino children (M/F = 28/19; mean/median age = 14.6/14.6 years) were the subjects of the trainee nurses. After the training, all nurses could perform all procedures independently. Otoscopic findings by ears included: normal (N = 77), otitis media with effusion (N = 2), myringosclerosis (N = 5), healed perforation (N = 6), perforation (N = 2) and retraction pocket/cholesteatoma (N = 2). Abnormal audiometric findings included: tympanogram (N = 4), DPOAE (N = 4) and screening audiometry (N = 0). Conclusion Training of local nurses has been shown to be robust and this methodology overcomes challenges of distant large-scale population otologic/audiometric assessment. [ABSTRACT FROM AUTHOR]

Objectives Schistosomiasis control is centred on preventive chemotherapy through mass drug administration (MDA). However, endemic countries continue to struggle to attain target coverage rates and patient compliance. In the Philippines, barangay health workers (BHWs) play a vital role in the coordination of MDA, acting as advocates, implementers, and educators. The aim of this study was to determine whether BHW knowledge and attitudes towards schistosomiasis and MDA is sufficient and correlated with resident knowledge and drug compliance. Methods A cross-sectional survey was conducted in 2015 among 2186 residents and 224 BHWs in the province of Northern Samar, the Philippines using a structured survey questionnaire. Results BHWs showed good familiarity on how schistosomiasis is acquired and diagnosed. Nevertheless, both BHWs and residents had poor awareness of the signs and symptoms of schistosomiasis, disease prevention, and treatment options. There was no correlation between the knowledge scores of the BHWs and the residents ( r = 0.080, p = 0.722). Kruskal–Wallis analysis revealed significant differences in BHW knowledge scores between the low (3.29, 95% confidence interval 3.16–3.36), moderate (3.61, 95% confidence interval 3.49–3.69), and high (4.05, 95% confidence interval 3.77–4.13) compliance village groups ( p = 0.002), with the high compliance areas having the highest mean knowledge scores. Conclusions This study highlights the importance of community health workers in obtaining the World Health Organization drug coverage rate of 75% and improving compliance with MDA in the community. Investing in the education of community health workers with appropriate disease-specific training is crucial if disease elimination is ultimately to be achieved. [ABSTRACT FROM AUTHOR]

Background Acute lower respiratory tract infections ( ALRI) are the leading cause of childhood mortality worldwide. Currently, most developing countries assign resources at a district level, and yet District Medical Officers have few tools for directing targeted interventions to high mortality or morbidity areas. Mapping of ALRI at the local level can guide more efficient allocation of resources, coordination of efforts and targeted interventions, which are particularly relevant for health management in resource-scarce settings. Methods An efficacy study of 11-valent pneumococcal vaccine was conducted in six municipalities in the Bohol Province of central Philippines from July 2000 to December 2004. Geocoded under-five pneumonia cases (using WHO classifications) were mapped to create spatial patterns of pneumonia at the local health unit (barangay) level. Results There were 2951 children with WHO-defined clinical pneumonia, of whom 1074 were severe or very severely ill, 278 were radiographic, and 219 were hypoxaemic. While most children with pneumonia were from urban barangays, there was a disproportionately higher distribution of severe/very severe pneumonia in rural barangays and the most severe hypoxaemic children were concentrated in the northern barangays most distant from the regional hospital. Conclusions Mapping of ALRI at the local administrative health level can be performed relatively simply. If these principles are applied to routinely collected IMCI classification of disease at the district level in developing countries, such efforts can form the basis for directing public health and healthcare delivery efforts in a targeted manner. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the Philippines, the current national control strategy for schistosomiasis is annual mass drug administration (MDA) with 40 mg/kg of praziquantel in all schistosomiasis-endemic villages with a prevalence >=10%. METHODS: A cross-sectional survey of schistosomiasis was conducted in 2012 on 18 221 individuals residing in 22 schistosomiasis-endemic villages in the province of Northern Samar. The prevalence of schistosomiasis, intensity of Schistosoma infection, and morbidity of disease were assessed. RESULTS: Despite an active schistosomiasis-control program in Northern Samar for >30 years, which included a MDA campaign in the last 5 years, the mean prevalence of schistosomiasis among 10 435 evaluated subjects was 27.1% (95% confidence interval [CI], 26.3%-28.0%), and the geometric mean intensity of infection among 2832 evaluated subjects was 17.2 eggs per gram of feces (95% CI, 16.4-18.1). Ultrasonography revealed high levels of schistosomiasis-induced morbidity in the schistosomiasis-endemic communities. Left lobe liver enlargement (>=70 mm) was evident in 89.3% of subjects. Twenty-five percent of the study population had grade II/III liver parenchyma fibrosis, and 13.3% had splenomegaly (>=100 mm). CONCLUSIONS: MDA on its own was insufficient to control the prevalence of schistosomiasis, intensity of Schistosoma infection, or morbidity of the disease. Alternative control measures will be needed to complement the existing national MDA program. [ABSTRACT FROM AUTHOR]

Correction to: BMC Research Notes (2021) 14:422 https://doi.org/10.1186/s13104-021-05834-y Following the publication of the original article [[1]], the authors requested to amend the article title from "Improving methods to measure comparable mortality cause (IMMCMC) gold standard verbal autopsy dataset" to "Improving methods to measure comparable mortality by cause (IMMCMC): gold standard verbal autopsy dataset". Improving methods to measure comparable mortality by cause (IMMCMC): gold standard verbal autopsy dataset. [Extracted from the article]

Obtaining schistosome infection data from thousands of humans and mammalian hosts in the Philippines, Steven Riley and colleagues find that mammalian acquisition, rather than transmission to snails, drives prevalence. [ABSTRACT FROM AUTHOR]

Viral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children. A cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated. Overall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1–2.8), human metapneumovirus (2.1, 1.4–3.2), rhinovirus (2.1, 1.8–2.6), and respiratory syncytial virus (1.6, 1.2–1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0–4.9). We determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy is the current global control strategy for schistosomiasis. The WHO target coverage rate is at least 75% for school-aged children. In the Philippines, the reported national coverage rate (43.5%) is far below the WHO target. This study examined the factors associated with non-compliance to mass drug administration. Methods: A cross-sectional survey was conducted in 2015 among 2189 adults in the province of Northern Samar, the Philippines using a structured face-to-face survey questionnaire. Results: The overall rate of non-compliance to mass drug administration (MDA) in the last treatment round was 27%. Females (aOR = 1.67, P = 0.033) were more likely to be non-compliant. Respondents who believed that schistosomiasis was acquired by open defecation and poor sanitation (aOR = 1.41, P = 0.015), and by drinking unclean water (aOR = 2.09, P = 0.001) were more likely to refuse treatment. Uncertainties on whether schistosomiasis can be treated (aOR = 2.39, P = 0.033), their fear of adverse reactions to praziquantel (aOR = 1.94, P = 0.021), misconceptions about alternative forms of treatment (aOR = 1.45, P = 0.037), and that praziquantel is used for purposes other than deworming (aOR = 2.15, P = 0.021) were all associated with a higher odd of non-compliance. In contrary, being a farmer (aOR = 0.62, P =0.038), participation in past MDA (aOR = 0.30, P < 0.001), informed about impending MDA (aOR = 0.08, P < 0.001), and having heard of schistosomiasis (aOR = 0.22, P = 0.045) were all significantly associated with reduced non-compliance. Conclusions: To improve drug compliance for schistosomiasis there is an urgent need for intensive health education campaigns before conducting MDA that would not only provide disease specific information, but also deal with prevailing misconceptions about transmission, prevention, treatment, and drug side-effects. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal conjugate vaccines (PCVs) have been shown in randomised controlled trials and epidemiological studies to prevent acute otitis media caused by vaccine serotype pneumococci, although their role in preventing complications of acute otitis media is less clear. We hypothesised that the 11-valent PCV would reduce the long-term sequelae of acute otitis media, including moderate-to-severe ear disease and hearing loss., Methods: This prospective cohort study, referred to as 11PCV study, included follow-up after 16-20 years of children previously enrolled in 2000-04, at age 6 weeks to 6 months, in the randomised, placebo-controlled, ARIVAC trial of 11-valent PCV for the prevention of radiographical pneumonia. The ARIVAC trial and this 11PCV study were conducted at six study centres in Bohol, Philippines. Ear disease was classified using video-otoscopy review and observations derived from the ear exam. The final classification of the worst ear disease was mild (ie, acute otitis media, otitis media with effusion, healed perforation, or tympanosclerosis), moderate (ie, dry perforation or adhesive otitis media), or severe (chronic suppurative otitis media). Hearing loss was assessed following a standard schema and classified according to the worst ear as mild (>15 to 30 dB puretone average) or moderate-to-profound (>30 dB pure tone average). We calculated the relative and absolute risk reduction in the primary outcome of moderate-to-severe ear disease and the secondary outcomes of mild or moderate-to-profound hearing loss in adolescents who previously received the 11-valent PCV compared with those who received placebo during infancy in ARIVAC., Findings: Of the 15 593 children assessed for eligibility in ARIVAC, 12 194 were randomly assigned and 8926 were alive and could be located for enrolment in this 11PCV study between Sept 19, 2016, and Dec 13, 2019. 8321 (4188 in the vaccine group and 4133 in the placebo group) completed follow-up of the 11PCV study by March 30, 2020, and had sufficient data to classify ear disease and be included in the primary outcome analysis. The primary outcome of the absolute risk reduction in moderate-to-severe ear disease in the vaccine group (310 [7·4%] of 4188) versus those in the placebo group (356 [8·6%] of 4133) was 1·2% (95% CI 0·0-2·4; p=0·046) and the relative risk reduction was 14·1% (0·0 to 26·0). There were no differences in secondary outcomes of mild hearing loss or moderate-to-profound hearing loss between the vaccine and placebo groups., Interpretation: The absolute risk reduction for moderate-to-severe ear disease in adolescence of 1·2% (12 per 1000 children) was almost three times higher than the 0·45% reduction (4·5 per 1000 children) in radiographical pneumonia in the first 2 years of life shown in ARIVAC. Administration of 11-valent PCV in infancy was associated with absolute and relative risk reductions in the sequelae of acute otitis media 16-20 years after the original ARIVAC trial., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests EAFS, PC-L, DMS, ML, VT, KMU, and KHC have received grants from the Bill & Melinda Gates Foundation for this study. EAFS reports grants and consulting fees to the institution from Merck and Pfizer; grants to the institution from AstraZeneca, Roche Pharmaceuticals, and Johnson and Johnson; and consulting fees to the institution from Sanofi Pasteur, Cidara Therapeutics, Adiago Therapeutics, and Nuance Pharmaceuticals; manuscript writing support from Pfizer and AstraZeneca; financial support for attending a meeting from AstraZeneca and Pfizer; and participation on a data monitoring committee for Abbvie, GlaxoSmithKline, and the Bill & Melinda Gates Foundation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The WHO estimates that close to 1.7 billion people worldwide have hearing loss; 34 million of whom are children, with 90% residing in low- and middle-income countries. While the effects of ear disease and hearing loss on language, academic, and behavioral development are established, there is remarkably little data on intellectual and other cognitive differences., Methods: Here we report results from an extension of a randomized controlled vaccination trial originally carried out between 2000 and 2004. Primary caregivers completed demographic and household questionnaires. Beginning in 2016, children were followed up for a hearing and ear disease evaluation. Participants also completed extensive cognitive testing, which included the domains of IQ, language, attention and processing speed, visual and visuospatial skills, and learning and memory. The association between ear disease and hearing loss and each of the cognitive outcomes was examined using multivariate linear regression models., Findings: We followed up 8926 children ages 14-19 years old. Children with hearing loss or ear disease had lower socioeconomic status compared to children without. However, even after controlling for a high number of covariates, all levels of ear disease or hearing loss were associated with clinically relevant reductions across all cognitive domains, though effect sizes were small. Even mild ear disease or hearing loss was associated with a -0.15 (95% CI: -0.20, -0.11) and a -0.23 (95% CI: -0.32, -0.14) standard deviation reduction, respectively, in IQ. The effects of ear disease and hearing loss were additive as children with both had the lowest cognitive scores., Interpretation: Untreated ear disease and hearing loss exert measurable effects on cognition that are able to be detected into the teenage years. Early identification of hearing loss and chronic ear disease may have lifelong benefits. Individuals with ear disease and/or hearing loss may require supports and services in addition to those related to speech and language therapy., Funding: The Bill and Melinda Gates Foundation OPP1142570., Competing Interests: ASM reports consulting fees from Biogen, Inc., and a grant from the STXBP1 Foundation, which are not related to the current work. EAFS reports grants and consulting fees to the institution from Merck & Co. and Pfizer Inc; grants to the institution from Astra Zeneca Inc., Roche Pharmaceuticals, and Johnson and Johnson; consulting fees to the institution from sanofi paseur, Cidara Therapeutics, Adiago Therapeutics and Nuance Pharmaceuticals; manuscript writing support from Pfizer Inc. and Astra Zeneca Inc.; support for attending a meeting Astra Zeneca Inc. and Pfizer Inc.; and participation on a DSMB from Abbvie Inc, GlaxoSmithKline plc, and Bill and Melinda Gates Foundation, all outside the submitted work. There are no other potential conflicts of interest related to this study., (© 2024 The Authors.)

Objective: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood., Study Design: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1])., Results: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months., Conclusion: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay., Competing Interests: Declaration of Competing Interest Authors have indicated they have no conflicts of interest other incentives relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Prenatal exposure to inflammation is related to the risk for cognitive impairment in offspring. However, mechanisms underlying the link between inflammatory cytokines at the maternal-fetal interface and human cognitive development are largely unknown. This study addressed this research gap by examining whether i) cytokines within the placenta are associated with different domains of neurocognitive development during infancy, and ii) if DHEA-S in cord blood mediates these associations. We also explored the role of early-life socioeconomic status (SES) in moderating the effect of fetal adrenal steroids on cognitive development in low- and middle-income country contexts. A cohort of 242 mother-infant dyads in Leyte, the Philippines participated in the study and all of them were followed from early pregnancy until 12-months. Concentrations of pro- and anti-inflammatory cytokines in the placenta, and DHEA-S in cord blood collected at delivery were evaluated. The multifactorial aspects of the infant's cognitive functioning were assessed based on the Bayley Scales of Infant Development, third edition (BSID-III). We used Structural Equation Modelling (SEM) with an orthogonal rotation to examine associated paths among latent variables of pro- and anti-inflammatory cytokines in the placenta, fetal neuroendocrine factors, and cognitive development. Pathway analyses showed that both pro- and anti-inflammatory cytokines in the placenta were indirectly related to cognitive (p < 0.05) and language developmental outcomes (p < 0.1) via DHEA-S in cord blood among the low SES group. Yet, we found no statistically significant indirect effect of pro- or anti-inflammatory cytokines on neurocognitive development among the high SES sub-sample. This study extends our understanding of how early-life socioeconomic conditions modify biological pathways underlying the relationship between prenatal factors and postpartum cognitive development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth., Methods: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors., Results: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004)., Conclusion: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities., (© 2023 International Federation of Gynecology and Obstetrics.)

Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear., Methods: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models., Results: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations., Conclusions: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide., Competing Interests: Potential conflicts of interest. A. G. serves on a scientific advisory board for Janssen. E. A. F. S. reports grants and consulting fees to the institution from Merck & Co and Pfizer Inc; grants to the institution from Astra Zeneca Inc, Roche Pharmaceuticals, and Johnson & Johnson; consulting fees to the institution from Sanofi Pasteur, Cidara Therapeutics, Adiago Therapeutics, and Nuance Pharmaceuticals; manuscript writing support from Pfizer Inc and Astra Zeneca Inc; support for attending a meeting Astra Zeneca Inc; and participation on a data and safety monitoring board from AbbVie Inc, GlaxoSmithKline plc, and the Bill and Melinda Gates Foundation. None of these are directly related to this manuscript. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Fetal alcohol spectrum disorder (FASD) captures the broad range of emotional, cognitive, behavioral, and congenital abnormalities associated with maternal alcohol consumption, and women living in resource-limited settings may be higher risk. This study aims to examine knowledge, attitudes, practices, and beliefs (KAPB) of women in Leyte, The Philippines regarding prenatal alcohol consumption., Methods: One hundred postpartum women were recruited from a birth cohort in Leyte. A prenatal alcohol use KAPB survey was constructed in Waray, the local language. The survey was administered in June-September 2019. Descriptive statistics, chi-squared test, and Fisher's exact test were used to analyze responses., Results: Seventy-five percent of subjects reported drinking tuba, a local palm wine, during pregnancy. Most participants (75%) did not believe tuba contained alcohol. Women who believed tuba contains no alcohol were more likely to drink tuba during pregnancy (81.3%) than women who believed tuba contains alcohol (56.0%), X 2 (1, N  = 100) = 6.41, p  = .011. Women who drank tuba during pregnancy were more likely to believe tuba has health benefits (60%) than women who did not drink tuba during pregnancy (12%), Fisher's exact p  < .05, citing increased red blood cell count and unproven antiparasitic qualities. Fifteen percent of subjects reported having fed their babies tuba. Nearly all (98%) were willing to attenuate tuba/alcohol consumption if told that this practice negatively impacts pregnancies., Conclusion: Misinformation about tuba appears widespread in Leyte. Educating women of reproductive age in Leyte regarding prenatal tuba use may lead to a reduction in tuba use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Huang, Neale, Darveau, Sagliba, Moreno, Urbina Paz, Tallo, McDonald, Jiz and Friedman.)

Background: Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies., Methods: Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth)., Results: Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4-6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2-2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0-2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old., Conclusions: RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2023.)

Background: Rhinoviruses (RVs) are among the most frequently detected viruses from hospitalized children with severe acute respiratory infections, being classified into RV-A, RV-B, and RV-C (4 clades: C, GAC1, GAC2, and A2). This study aimed to compare the clinical characteristics and respiratory tract illness severity between the RV species and RV-C clades in children in primary care and hospital settings in rural communities in the Philippines., Methods: Clinical samples and information of children <5 years old in the Philippines were collected from 2014 to 2016. The samples were tested by reverse-transcription polymerase chain reaction (RT-PCR) targeting the 5'-untranslated region. PCR-positive samples were sequenced, and RV species were identified by phylogenetic analysis., Results: Overall, 3680 respiratory tract illness episodes in 1688 cohort children were documented; 713 of those were RV positive and identified as RV-A (n = 271), RV-B (n = 47), and RV-C (n = 395: C [n = 76], GAG1 [n = 172], GAG2 [n = 8], A2 [n = 138], and unidentified [n = 1]). Severe illnesses, low oxygen saturation, cough, and wheezing were more common in patients with RV-C, especially with GAC1, than in those with RV-A or RV-B. Furthermore, severe illness was significantly more common in RV-C (GAC1)-positive cases than in RV-A-positive cases (odds ratio, 2.61 [95% CI, 1.17-4.13])., Conclusions: Children infected with RV-C had more severe illnesses than children infected with RV-A and RV-B. Moreover, emerging clades of RV-C were associated with increased severity., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Soil-transmitted helminth (STH) infections are a significant public health problem affecting over 900 million people globally. Health education has been shown to complement mass drug administration (MDA) for the control of these intestinal worms. We reported recently results of a cluster randomised control trial (RCT) showing the positive impact of the "The Magic Glasses Philippines (MGP)" health education package in reducing STH infections among schoolchildren in intervention schools with ≤15% STH baseline prevalence in Laguna province, the Philippines. To inform decision making on the economic implications of the MGP, we evaluated the in-trial costs and then quantified the costs of scaling up the intervention both regionally and nationally., Methods: Costs were determined for the MGP RCT conducted in 40 schools in Laguna province. We estimated the total cost and the costs incurred per student for the actual RCT and the total costs for regional and national scale-up in all schools regardless of STH endemicity. The costs associated with the implementation of standard health education (SHE) activities and mass drug administration (MDA) were determined with a public sector perspective., Findings: The cost per participating student in the MGP RCT was Php 58.65 (USD 1.15) but if teachers instead of research staff had been involved, the estimated cost would have been considerably lower at Php 39.45 (USD 0.77). Extrapolating the costs for regional scale-up, the costs per student were estimated to be Php 15.24 (USD 0.30). As it is scaled up at the national level to include more schoolchildren, the estimated cost was increased at Php 17.46 (USD 0.34). In scenario 2 and 3, consistently, labour/salary costs associated with the delivery of the MGP contributed most to overall programme expenditure. Furthermore, the estimated average cost per student for SHE and MDA were Php 117.34 (USD 2.30) and Php 58.17 (USD 1.14), respectively. Using national scale up estimates, the cost of combining the MGP with SHE and MDA was Php 192.97 (USD 3.79)., Interpretation: These findings suggest that the integration of MGP into the school curriculum would be an affordable and scalable approach to respond to the continuous burden of STH infection among schoolchildren in the Philippines., Funding: National and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland., Competing Interests: All authors declare no competing interests., (© 2022 The Author(s).)

Background: Soil-transmitted helminth (STH) infections are still prevalent among schoolchildren in the Philippines. We evaluated the risk factors associated with STH and the relationship between STH and nutritional indices among schoolchildren aged 9-10 years in Laguna province, the Philippines., Methods: We used the baseline data from 40 schools enrolled in a randomised controlled trial of the Magic Glasses Philippines health education package. Data on demographic and socio-economic variables, and STH related knowledge, attitudes and practices, were obtained through a questionnaire. Stool samples were collected and assessed for STH egg presence using the Kato-Katz technique. Haemoglobin levels and height and weight of study participants were also determined. The generalized estimating equations approach was used to construct logistic regression models to assess STH-associated risk factors, and the association between any STH infection and anaemia, child stunting, wasting and being underweight. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000508471)., Findings: Among 1,689 schoolchildren, the prevalence of any STH was 23%. The prevalence of anaemia, stunting, being underweight and wasting was 13%, 20.2%, 19% and 9.5%, respectively. Age, socio-economic status, rural/urban classification of schools and knowledge of STH were significant risk factors for acquiring a STH infection. Moreover, infections with any STH were significantly associated with stunting (P = <0.001) and being underweight (P = <0.003), but not wasting (P = 0.375) or anaemia (P = 0.462) after controlling for confounding covariates., Conclusion: The study findings emphasise the need for sustainable deworming in tandem with other measures such as the provision of health education, improvements in sanitation and hygiene, and nutritional programs in order to control STH infections and improve morbidity outcomes in schoolchildren., Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12616000508471)., Competing Interests: The authors have declared that no competing interests exist. Author Remigio M Olveda was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Background: Soil-transmitted helminths (STH) cause substantial disease and disability globally. Health education has proven complementary to school-based drug administration programs for STH control. We determined the generalizability of the impact of "The Magic Glasses" health education package for STH prevention in schoolchildren in Laguna province, the Philippines, having previously shown its positive impact in China., Methods: We conducted a cluster-randomised controlled trial, in schoolchildren, aged 9-10 years, across 40 schools over one year. Schools were randomly assigned either to the "Magic Glasses Philippines" health education intervention package (consisting of a cartoon video, classroom discussions, drawing and essay competition) complementing the standard health education activities of the Philippines Departments of Health and Education, or to a control group, which involved only the standard health education activities. The primary trial outcomes were the proportion of STH infected schoolchildren and their knowledge, attitude and behaviour of STH assessed in both groups at baseline and through two follow-up surveys undertaken immediately prior to the semi-annual national mass administration of albendazole. The outcomes between the study arms were compared using generalized estimating equation models, accounting for clustering at the school level. The trial is registered with Australian New Zealand Clinical Trials Registry number: ACTRN12616000508471., Findings: At follow-up assessments, the mean knowledge and behaviour scores in the intervention group were, respectively, 5·3 (95% confidence interval [CI]:4·2-6·5; p=<0.001) and 1·1 (95% CI: 0·4-1·7; p=0.002) percentage points higher than the control group. There was no overall effect on helminth infections (any STH; adjusted odds ratio [aOR]:1·0; 95% CI: 0·8-1·3; p=0·856), Ascaris lumbricoides; aOR:1·0; 95% CI: 0·7-1·6; p=0·894, or Trichuris trichiura; aOR:1·7; 95% CI: 0·9-1·6; p=0·315) but sub-group analysis showed a 60% reduction in the odds of any STH infection resulting from the "Magic Glasses" intervention in schools with a baseline prevalence ≤15% (aOR: 0·4; 95% CI: 0·2-0·7; p=0·001)., Interpretation: The health-education package demonstrated a modest but statistically significant impact on the students' overall STH knowledge and changes in their behaviour but was only effective in preventing STH infections in intervention schools where the baseline prevalence was ≤15%., Funding: National Health and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland., Competing Interests: All authors declare no competing interests., (© 2021 The Authors.)

Background: Soil-transmitted helminth (STH) infections have long been an important public health concern in the Philippines. In this review, we describe the current status of STH infections there and highlight the control efforts undertaken to reduce STH burden., Main Text: A nationwide STH mass drug administration (MDA) programme was started in 2006 but the overall STH prevalence remains stubbornly high across the Philippines, ranging from 24.9% to 97.4%. The continued increase in the prevalence may have been due to the challenges related to MDA implementation which include the lack of people's awareness about the importance of regular treatment, misconceptions about the MDA strategy, lack of confidence on the drugs used, fear of adverse events and general distrust of government programs. There are existing water, sanitation and hygiene (WASH) programmes implemented in communities [e.g., Community-Led Total Sanitation (CLTS) program and providing toilet bowls and provision of subsidy for latrine construction] and schools [e.g., WASH in School (WINS) program], but sustained implementation is required to achieve expected outcomes. Although WASH in general is being taught in schools, integration of STH as a disease and community problem in the current public elementary school curriculum is still inadequate. The Integrated Helminth Control Program (IHCP) currently implemented in the country, which is focused on improved sanitation and personal hygiene, health education and preventive chemotherapy, will require continuous appraisal. The sustainability of this programme still continues to be a challenge., Conclusions: Despite the major efforts to control STH infections for almost two decades in the Philippines, persistently high STH prevalence has been reported across the country, which is likely due to suboptimal MDA coverage and limitations in WASH and health education programs. Sustainable delivery of integrated control approaches will continue to play a pivotal role in the control and elimination of STH in the Philippines.

Introduction: A cohort of 12 000 children in the Philippines who had enrolled in a 2000-2004 (current ages 16 to 20 years) Phase 3 11-valent pneumococcal conjugate vaccine for the prevention of radiographically confirmed pneumonia are now being asked to participate in a separate study (expected completion date September 2021) to assess the cohort's current long-term audiometric and otologic status. This new study would allow assessments of the utility of the pneumococcal vaccine in conferring its protective effects on the long-term sequelae of otitis media (OM), if any. Lack of trained local healthcare providers in otolaryngology/audiology and testing equipment in Bohol, Philippines, necessitates the development of a distinct methodology that would lead to meaningful data analysis., Methods and Analysis: Reliable data collection and transfer are achieved by a US otolaryngologist/audiologist team training local nurses on all procedures in a didactic and hands-on process. An assortment of portable otolaryngologic and audiologic equipment suitable for field testing has been acquired, including an operating otoscope (Welch-Allyn), a video-otoscope (JedMed), a tympanometer with distortion product otoacoustic emission measurements (Path Sentiero) and a screening audiometer (HearScreen). Data will then be uploaded to a Research Electronic Data Capture database in the USA.Tympanometric and audiologic data will be codified through separate conventional algorithms. A team of paediatric otolaryngology advanced practice providers (APPs) have been trained and validated in interpreting video otoscopy. The protocol for classification of diagnostic outcome variables based on video otoscopy and tympanometry has been developed and is being used by APPs to evaluate all otoscopy data., Ethics and Dissemination: The study was approved by the Research Institute of Tropical Medicine, Alabang, Manila, Philippines, and the institutional review board and the Colorado Multiple Institutional Review Board of the University of Colorado School of Medicine, Aurora, Colorado, USA.Research results will be made available to children and their caregivers with abnormal audiologic outcomes, the funders and other researchers., Trial Registration Number: ISRCTN 62323832; Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care., Methods and Analysis: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies., Ethics and Dissemination: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings., Trial Registration Number: NCT04285021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background and Objectives: Despite a substantial reduction in the mortality rate of children under 5 years in the past 25 years, pneumonia remains the single-largest infectious cause of child deaths worldwide. This study explored the chronological order of visited healthcare facilities and practitioners, and the factors affecting mothers' intention to seek care before the hospitalisation of children with pneumonia., Methods and Analysis: A qualitative research design was employed using theory of planned behaviour as a framework for the analysis. Using purposive sampling technique, 11 mothers, whose children under 5 years old were hospitalised with severe pneumonia, were recruited for individual semi-structured interviews. Their socio-demographic information was analysed using descriptive statistics., Results: Mothers brought their sick children to multiple facilities, and 1 to 19 days had passed before hospitalisation. We identified four major factors determining mothers' intentions: (1) doing something useful for the sick child, (2) expecting the child to receive the necessary assessment and treatment, (3) accepting advice to visit a healthcare facility and be referred to a hospital and (4) considering issues and benefits associated with hospitalisation. Mothers noticed their children's unusual symptoms and monitored them while applying home remedies. They also took their children to traditional healers despite knowing that the treatments were not necessarily effective. Mothers expected children to be checked by health professionals and listened to advice from family members regarding the facilities to visit, and from healthcare staff to be referred to a hospital. Financial issues and the double burden of housework and caring for the hospitalised child were mothers' major concerns about hospitalisation., Conclusion: Children were hospitalised after several days because they visited multiple healthcare facilities, including traditional healers. Improving care quality at healthcare facilities and reducing financial and mothers' burden may reduce the hospitalisation delay for children with pneumonia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with S. japonicum in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women ( n = 15 each) and lactating postpartum women ( n  = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC 0-24 ) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis., (Copyright © 2020 Bustinduy et al.)

Background: Repeated mass drug administration (MDA) of antihelminthics to at-risk populations is still the main strategy for the control of soil-transmitted helminth (STH) infections. However, MDA, as a stand-alone intervention, does not prevent reinfection. Accordingly, complementary measures to prevent STH reinfection, such as health education and improved sanitation, as part of an integrated control approach, are required to augment the effectiveness of MDA for optimal efficiency and sustainability., Objective: The aim of this study is to determine the impact and generalizability of a school-based health education package entitled The Magic Glasses for STH prevention in the Philippines., Methods: We conducted a cluster randomized controlled intervention trial, involving 2020 schoolchildren aged 9-10 years, in 40 schools in Laguna Province, Philippines, to evaluate the impact of the school-based health education package for the prevention of STHs. The trial was conducted over the course of 1 year (June 2016 to July 2017). A total of 20 schools were randomly assigned to the intervention arm, in which The Magic Glasses Philippines health education package was delivered with the standard health education activities endorsed by the Philippines Department of Health (DOH) and the Department of Education (DepEd). The other 20 schools comprised the control arm of the study, where the DOH/DepEd's standard health education activities were done. At baseline, parasitological assessments and a knowledge, attitude, and practice survey were carried out in all schools. In addition, height, weight, and hemoglobin levels were obtained from each child (after parental consent), and their school attendance and academic performance in English and mathematics were accessed from the school records. The baseline and 2 follow-up surveys were completed using the same study measurements and quality-control assessments., Results: Key results from this cluster randomized intervention trial will shed light on the impact that The Magic Glasses health education package will have against STH infections in schoolchildren in the province of Laguna, located on the Island of Luzon, in the Calabarzon Region of the Philippines., Conclusions: The results of the trial will be used to assess the generalizability of the impact of The Magic Glasses health education package in different epidemiological and cultural settings, providing evidence for translation of this health education package into public health policy and practice in the Asian region and beyond., Trial Registration: Australian New Zealand Clinical Trials Registry number ACTRN12616000508471; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368849., International Registered Report Identifier (irrid): DERR1-10.2196/18419., (©Mary Lorraine S Mationg, Gail M Williams, Veronica L Tallo, Remigio M Olveda, Eindra Aung, Portia Alday, Mark Donald Reñosa, Chona Mae Daga, Jhoys Landicho, Maria Paz Demonteverde, Eunice Dianne Santos, Thea Andrea Bravo, Franziska A Angly Bieri, Yuesheng Li, Archie C A Clements, Peter Steinmann, Kate Halton, Donald E Stewart, Donald P McManus, Darren J Gray. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.06.2020.)

Background: Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers' knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers' intent to vaccinate their child., Methods: From 2015 to 2017, infants 0-11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6-11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis., Results: In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample., Conclusion: Intent to vaccinate infants aged 6-11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants., Methods: The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015-16 and 2016-17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015-16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses., Findings: Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2·6 (95% CI 2·0-3·6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis., Interpretation: If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes., Funding: US Centers for Disease Control and Prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We evaluated the association between etiology of maternal anemia and iron status throughout infancy., Methods: Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated., Results: Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status., Conclusions: Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.