The Impact of Prenatal Alcohol Exposure on Longitudinal Growth, Nutritional Status, and Insulin-Like Growth Factor 1 in Early Childhood in Leyte, the Philippines.

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.

Early-life matters: The role of fetal adrenal steroids in the relationship between cytokines within the placental circulation and cognitive development among infants in the Philippines.

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.

Impaired Intrauterine Growth in the Context of Maternal Hookworm Infection During Gestation.

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.

Incidence of lower respiratory tract infection and associated viruses in a birth cohort in the Philippines.

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.

Risk of Transmission and Viral Shedding From the Time of Infection for Respiratory Syncytial Virus in Households.

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.

"The staff are not motivated anymore": Health care worker perspectives on the Integrated Management of Childhood Illness (IMCI) program in the Philippines.

BACKGROUND: Studies focusing on the Integrated Management of Childhood Illness (IMCI) program in the Philippines are limited, and perspectives of frontline health care workers (HCWs) are largely absent in relation to the introduction and current implementation of the program. Here, we describe the operational challenges and opportunities described by HCWs implementing IMCI in five regions of the Philippines. These perspectives can provide insights into how IMCI can be strengthened as the program matures, in the Philippines and beyond. METHODS: In-depth interviews (IDIs) were conducted with HCWs (n = 46) in five provinces (Ilocos Sur, Quezon, National Capital Region, Bohol and Davao), with full transcription and translation as necessary. In parallel, data collectors observed the status (availability and placement) of IMCI-related materials in facilities. All data were coded using NVivo 12 software and arranged along a Social Ecological Model. RESULTS: HCWs spoke of the benefits of IMCI and discussed how they developed workarounds to ensure that integral components of the program could be delivered in frontline facilities. Five key challenges emerged in relation to IMCI implementation in primary health care (PHC) facilities: 1) insufficient financial resources to fund program activities, 2) inadequate training, mentoring and supervision among and for providers, 3) fragmented leadership and governance, 4) substandard access to IMCI relevant written documents, and 5) professional hierarchies that challenge fidelity to IMCI protocols. CONCLUSION: Although the IMCI program was viewed by HCWs as holistic and as providing substantial benefits to the community, more viable implementation processes are needed to bolster acceptability in PHC facilities.

Population Pharmacokinetics of Praziquantel in Pregnant and Lactating Filipino Women Infected with Schistosoma japonicum.

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 (AUC0-24) 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.

Association Between Preceding Viral Respiratory Infection and Subsequent Respiratory Illnesses Among Children: A Prospective Cohort Study in the Philippines.

Background: Acute respiratory infection (ARI) is of great concern in public health. It remains unclear whether viral infections can affect the host's susceptibility to subsequent ARIs. Methods: A prospective cohort study on ARIs of children below 5 years old was conducted in the Philippines from 2014 to 2016. The respiratory symptoms were recorded daily, and nasopharyngeal swabs were collected at both household and health facilities. The specimens were tested for respiratory viruses. We then determined whether viral etiology was associated with the severity of the present ARI and whether previous viral infections was associated with subsequent ARIs. Results: A total of 3851 children and 16337 ARI episodes were enrolled and recorded, respectively. Samples were collected from 24% of all ARI episodes; collection rate at the healthcare facilities was 95%. Enterovirus D68, rhinovirus species C, and respiratory syncytial virus were significantly associated with severe ARIs. The risk for subsequent ARIs was significantly enhanced after infections with adenovirus, influenza A virus, parainfluenza virus type 4, and rhinovirus species C. Conclusions: This study revealed that viral etiology plays a significant role in the severity of the present ARI and that viral infection affects the host's susceptibility to subsequent ARIs.

On the estimation of population cause-specific mortality fractions from in-hospital deaths.

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.

Maternal anemia type during pregnancy is associated with anemia risk among offspring during infancy.

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.

Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment.

Background: To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. Objectives: The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. Methods: We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin <30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin ≥30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. Results: Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 µg/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 µg/L; P = 0.042). Conclusions: Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy. This trial was registered at www.clinicaltrials.gov as NCT00486863.

Assessing the quality of medical death certification: a case study of concordance between national statistics and results from a medical record review in a regional hospital in the Philippines.

BACKGROUND: Medical certificates of cause of death (MCCOD) issued by hospital physicians are a key input to vital registration systems. Deaths certified by hospital physicians have been implicitly considered to be of high quality, but recent evidence suggests otherwise. We conducted a medical record review (MRR) of hospital MCCOD in the Philippines and compared the cause of death concordance with certificates coded by the Philippines Statistics Authority (PSA). METHODS: MCCOD for adult deaths in Bohol Regional Hospital (BRH) in 2007-2008 and 2011 were collected and reviewed by a team of study physicians. Corresponding MCCOD coded by the PSA were linked by a hospital identifier. The study physicians wrote a new MCCOD using the patient medical record, noted the quality of the medical record to produce a cause of death, and indicated whether it was necessary to change the underlying cause of death (UCOD). Chance-corrected concordance, cause-specific mortality fraction (CSMF) accuracy, and chance-corrected CSMF were used to examine the concordance between the MRR and PSA. RESULTS: A total of 1052 adult deaths were linked between the MRR and PSA. Median chance-corrected concordance was 0.73, CSMF accuracy was 0.85, and chance-corrected CSMF accuracy was 0.58. 74.8% of medical records were deemed to be of high enough quality to assign a cause of death, yet study physicians indicated that it was necessary to change the UCOD in 41% of deaths, 82% of which required addition of a new UCOD. CONCLUSIONS: Medical records were generally of sufficient quality to assign a cause of death and concordance between the PSA and MRR was reasonably high, suggesting that routine mortality statistics data are reasonably accurate for describing population level causes of death in Bohol. While overall agreement between the PSA and MRR in major cause groups was sufficient for public health purposes, improvements in death certification practices are recommended to help physicians differentiate between treatable (immediate) COD and COD that are important for public health surveillance.

Collecting verbal autopsies: improving and streamlining data collection processes using electronic tablets.

BACKGROUND: There is increasing interest in using verbal autopsy to produce nationally representative population-level estimates of causes of death. However, the burden of processing a large quantity of surveys collected with paper and pencil has been a barrier to scaling up verbal autopsy surveillance. Direct electronic data capture has been used in other large-scale surveys and can be used in verbal autopsy as well, to reduce time and cost of going from collected data to actionable information. METHODS: We collected verbal autopsy interviews using paper and pencil and using electronic tablets at two sites, and measured the cost and time required to process the surveys for analysis. From these cost and time data, we extrapolated costs associated with conducting large-scale surveillance with verbal autopsy. RESULTS: We found that the median time between data collection and data entry for surveys collected on paper and pencil was approximately 3 months. For surveys collected on electronic tablets, this was less than 2 days. For small-scale surveys, we found that the upfront costs of purchasing electronic tablets was the primary cost and resulted in a higher total cost. For large-scale surveys, the costs associated with data entry exceeded the cost of the tablets, so electronic data capture provides both a quicker and cheaper method of data collection. CONCLUSIONS: As countries increase verbal autopsy surveillance, it is important to consider the best way to design sustainable systems for data collection. Electronic data capture has the potential to greatly reduce the time and costs associated with data collection. For long-term, large-scale surveillance required by national vital statistical systems, electronic data capture reduces costs and allows data to be available sooner.

Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods.

BACKGROUND: This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. METHODS/DESIGN: We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. DISCUSSION: The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.

Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children.

Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from -14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs.

Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines.

BACKGROUND: Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. FINDINGS: Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. CONCLUSIONS: The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

What is the optimal recall period for verbal autopsies? Validation study based on repeat interviews in three populations.

BACKGROUND: One key contextual feature in Verbal Autopsy (VA) is the time between death and survey administration, or recall period. This study quantified the effect of recall period on VA performance by using a paired dataset in which two VAs were administered for a single decedent. METHODS: This study used information from the Population Health Metrics Research Consortium (PHMRC) Study, which collected VAs for "gold standard" cases where cause of death (COD) was supported by clinical criteria. This study repeated VA interviews within 3-52 months of death in PHMRC study sites in Andhra Pradesh, India, and Bohol and Manila, Philippines. The final dataset included 2113 deaths interviewed twice and with recall periods ranging from 0 to 52 months. COD was assigned by the Tariff method and its accuracy determined by comparison with the gold standard COD. RESULTS: The probability of a correct diagnosis of COD decreased by 0.55 % per month in the period after death. Site of data collection and survey module also affected the probability of Tariff Method correctly assigning a COD. The probability of a correct diagnosis in VAs collected 3-11 months after death will, on average, be 95.9 % of that in VAs collected within 3 months of death. CONCLUSIONS: These findings suggest that collecting VAs within 3 months of death may improve the quality of the information collected, taking the need for a period of mourning into account. This study substantiates the WHO recommendation that it is reasonable to collect VAs up to 1 year after death providing it is accepted that probability of a correct diagnosis is likely to decline month by month during this period.

The paradox of verbal autopsy in cause of death assignment: symptom question unreliability but predictive accuracy.

BACKGROUND: We believe that it is important that governments understand the reliability of the mortality data which they have at their disposable to guide policy debates. In many instances, verbal autopsy (VA) will be the only source of mortality data for populations, yet little is known about how the accuracy of VA diagnoses is affected by the reliability of the symptom responses. We previously described the effect of the duration of time between death and VA administration on VA validity. In this paper, using the same dataset, we assess the relationship between the reliability and completeness of symptom responses and the reliability and accuracy of cause of death (COD) prediction. METHODS: The study was based on VAs in the Population Health Metrics Research Consortium (PHMRC) VA Validation Dataset from study sites in Bohol and Manila, Philippines and Andhra Pradesh, India. The initial interview was repeated within 3-52 months of death. Question responses were assessed for reliability and completeness between the two survey rounds. COD was predicted by Tariff Method. RESULTS: A sample of 4226 VAs was collected for 2113 decedents, including 1394 adults, 349 children, and 370 neonates. Mean question reliability was unexpectedly low (kappa = 0.447): 42.5 % of responses positive at the first interview were negative at the second, and 47.9 % of responses positive at the second had been negative at the first. Question reliability was greater for the short form of the PHMRC instrument (kappa = 0.497) and when analyzed at the level of the individual decedent (kappa = 0.610). Reliability at the level of the individual decedent was associated with COD predictive reliability and predictive accuracy. CONCLUSIONS: Families give coherent accounts of events leading to death but the details vary from interview to interview for the same case. Accounts are accurate but inconsistent; different subsets of symptoms are identified on each occasion. However, there are sufficient accurate and consistent subsets of symptoms to enable the Tariff Method to assign a COD. Questions which contributed most to COD prediction were also the most reliable and consistent across repeat interviews; these have been included in the short form VA questionnaire. Accuracy and reliability of diagnosis for an individual death depend on the quality of interview. This has considerable implications for the progressive roll out of VAs into civil registration and vital statistics (CRVS) systems.

National Influenza Surveillance in the Philippines from 2006 to 2012: seasonality and circulating strains.

BACKGROUND: The results of routine influenza surveillance in 13 regions in the Philippines from 2006 to 2012 are presented, describing the annual seasonal epidemics of confirmed influenza virus infection, seasonal and alert thresholds, epidemic curve, and circulating influenza strains. METHODS: Retrospective analysis of Philippine influenza surveillance data from 2006 to 2012 was conducted to determine seasonality with the use of weekly influenza positivity rates and calculating epidemic curves and seasonal and alert thresholds using the World Health Organization (WHO) global epidemiological surveillance standards for influenza. RESULTS: Increased weekly influenza positive rates were observed from June to November, coinciding with the rainy season and school opening. Two or more peaks of influenza activity were observed with different dominant influenza types associated with each peak. A-H1N1, A-H3N2, and two types of B viruses circulated during the influenza season in varying proportions every year. Increased influenza activity for 2012 occurred 8 weeks late in week 29, rather than the expected week of rise of cases in week 21 as depicted in the established average epidemic curve and seasonal threshold. The intensity was severe going above the alert threshold but of short duration. Southern Hemisphere vaccine strains matched circulating influenza virus for more surveillance years than Northern Hemisphere vaccine strains. CONCLUSIONS: Influenza seasonality in the Philippines is from June to November. The ideal time to administer Southern Hemisphere influenza vaccine should be from April to May. With two lineages of influenza B circulating annually, quadrivalent vaccine might have more impact on influenza control than trivalent vaccine. Establishment of thresholds and average epidemic curve provide a tool for policy-makers to assess the intensity or severity of the current influenza epidemic even early in its course, to help plan more precisely resources necessary to control the outbreak. Influenza surveillance activities should be continued in the Philippines and funding for such activities should already be incorporated into the Philippine health budget.

Can mass drug administration lead to the sustainable control of schistosomiasis?

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.