Publications by authors named "Socorro P Lupisan"

26 Publications

  • Page 1 of 1

Development of a novel in vitro assay to evaluate environmental water using an IL-8 reporter cell line.

EXCLI J 2020 21;19:1054-1063. Epub 2020 Jul 21.

Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

The IL-8 luciferase reporter cell line, THP-G8 cells, used in the sensitization test, OECD442E, can respond to a variety of stimuli other than haptens, such as lipopolysaccharide (LPS), other bacterial toxins, and detergents. Considering these characteristics, we examined the ability of the IL-8 luciferase assay using THP-G8 cells to evaluate water pollution. We first stimulated THP-G8 cell with various Toll-like receptor (TLR) agonists and nucleotide-binding oligomerization domain-like receptor (NLR) agonists, and found that TLR1, 2, 4, 5, 6 agonists and NOD 1, 2 agonists significantly augmented IL-8 luciferase activity (IL8LA). Then, we examined the detection threshold of LPS by THP-G8 cells, and found it 0.4 EU/ml. Next, we examined whether THP-G8 cells can differently respond to a variety of sources of environmental water around Sendai, Japan and Manila, Philippine and whether there is a correlation between the IL8LA of different sources of water and their level of endotoxin assessed by the LAL assay. There was a clear trend that the IL8LA was lower in the upper stream and higher in the downstream in both Japan and Philippine. Moreover, there was a strong correlation between the IL8LA of the environmental water and its endotoxin level. Finally, using N-acetyl-L-cysteine, an antioxidant/radical scavenger, and polymyxin B that neutralizes endotoxin, we demonstrated that there was a difference in the suppressive effects by them between the water from Japan and that from Philippine. These data suggest the potential of the IL-8 luciferase assay for evaluating environmental water pollution both quantitatively and qualitatively.
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http://dx.doi.org/10.17179/excli2020-2104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527499PMC
July 2020

Factors affecting mothers' intentions to visit healthcare facilities before hospitalisation of children with pneumonia in Biliran province, Philippines: a qualitative study.

BMJ Open 2020 08 26;10(8):e036261. Epub 2020 Aug 26.

Epidemiology and Biostatics, Research Institute for Tropical Medicine, Muntinlupa City, Philippines.

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.
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http://dx.doi.org/10.1136/bmjopen-2019-036261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451295PMC
August 2020

Genetic diversity of species A rotaviruses detected in clinical and environmental samples, including porcine-like rotaviruses from hospitalized children in the Philippines.

Infect Genet Evol 2020 11 17;85:104465. Epub 2020 Jul 17.

Department of Virology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Rotaviruses are the major cause of severe acute diarrhea in infants and young children. Rotaviruses exhibit zoonosis and thereby infect both humans and animals. Viruses detected in urban rivers possibly reflect the presence of circulating viruses in the catchment. The present study investigates the genetic diversity of species A rotaviruses detected from river water and stool of hospitalized children with acute diarrhea in Tacloban City, the Philippines. Species A rotaviruses were detected by real-time RT-PCR and their genotypes were identified by multiplex PCR and sequencing of partial regions of VP7 and VP4. Rotaviruses were detected in 85.7% (30/35) of the river water samples and 62.7% (151/241) of the clinical samples. Genotypes of VP7 in the river water samples were G1, G2, G3, G4, G5, and G9, and those of VP4 were P[3], P[4], P[6], P[8], and P[13]. Genotypes of viruses from the clinical samples were G2P[4], G1P[8], G3P[8], G4P[6], G5P[6], and G9P[8]. Among those, G2P[4] in clinical samples (77.9%, 81/104) and P[4] of VP4 in river water samples (67.5%, 56/83)) were the most frequently detected rotavirus genotypes. However, G5 was the more frequently detected than G2 in the river water samples (42% vs. 13%) which may be originated from porcine rotavirus. Sequence analyses of eleven gene segments revealed one G5P[6] and two G4P[6] rotaviruses in the clinical samples, wherein, several gene segments were closely related to porcine rotaviruses. The constellation of these rotavirus genes suggests the emergence of reassortment between human and porcine rotavirus due to interspecies transmission. Although two commercial rotavirus vaccines are available now, these vaccines are designed to confer immunity against the major human rotaviruses. Constant monitoring of viral variety in populated areas where humans and domestic animals live in close proximity provides vital information related to the diversity of rotaviruses in a human population.
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http://dx.doi.org/10.1016/j.meegid.2020.104465DOI Listing
November 2020

Aetiology and risks factors associated with the fatal outcomes of childhood pneumonia among hospitalised children in the Philippines from 2008 to 2016: a case series study.

BMJ Open 2019 03 30;9(3):e026895. Epub 2019 Mar 30.

Virology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: Pneumonia remains the leading cause of hospitalisations and deaths among children aged <5 years. Diverse respiratory pathogens cause acute respiratory infections, including pneumonia. Here, we analysed viral and bacterial pathogens and risk factors associated with death of hospitalised children.

Design: A 9-year case series study.

Setting: Two secondary-care hospitals, one tertiary-care hospital and one research centre in the Philippines.

Participants: 5054 children aged <5 years hospitalised with severe pneumonia.

Methods: Nasopharyngeal swabs for virus identification, and venous blood samples for bacterial culture were collected. Demographic, clinical data and laboratory findings were collected at admission time. Logistic regression analyses were performed to identify the factors associated with death.

Results: Of the enrolled patients, 57% (2876/5054) were males. The case fatality rate was 4.7% (238/5054), showing a decreasing trend during the study period (p<0.001). 55.0% of the patients who died were either moderately or severely underweight. Viruses were detected in 61.0% of the patients, with respiratory syncytial virus (27.0%) and rhinovirus (23.0%) being the most commonly detected viruses. In children aged 2-59 months, the risk factors significantly associated with death included age of 2-5 months, sensorial changes, severe malnutrition, grunting, central cyanosis, decreased breath sounds, tachypnoea, fever (≥38.5°C), saturation of peripheral oxygen <90%, infiltration, consolidation and pleural effusion on chest radiograph.Among the pathogens, adenovirus type 7, seasonal influenza A (H1N1) and positive blood culture for bacteria were significantly associated with death. Similar patterns were observed between the death cases and the aforementioned factors in children aged <2 months.

Conclusion: Malnutrition was the most common factor associated with death and addressing this issue may decrease the case fatality rate. In addition, chest radiographic examination and oxygen saturation measurement should be promoted in all hospitalised patients with pneumonia as well as bacteria detection to identify patients who are at risk of death.
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http://dx.doi.org/10.1136/bmjopen-2018-026895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475207PMC
March 2019

Age-specific incidence rates and risk factors for respiratory syncytial virus-associated lower respiratory tract illness in cohort children under 5 years old in the Philippines.

Influenza Other Respir Viruses 2019 07 19;13(4):339-353. Epub 2019 Mar 19.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Respiratory syncytial virus (RSV) is one of the main viral causes of lower respiratory tract illness (LRTI), especially in young children. RSV vaccines, including maternal and infant vaccines, are under development; however, more epidemiological studies are needed to develop effective vaccination strategies.

Objectives: To estimate detailed age-specific incidence rates and severity of RSV-associated LRTI (RSV-LRTI) using data from a community-based prospective cohort study in the Philippines.

Patients/methods: Cohort children who visited health facilities due to acute respiratory symptoms were identified, and nasopharyngeal swabs were collected to detect RSV. The severity of RSV-LRTI was assessed using the severity definition proposed by the World Health Organization. Risk factors for developing RSV-LRTI and contribution of SpO measurement were also evaluated.

Results: A total of 395 RSV episodes which occurred in children aged 2-59 months were categorised as 183 RSV-LRTI, 72 as severe RSV-LRTI and 29 as very severe RSV-LRTI. Children aged 3-5 months had the highest incidence rate of RSV-LRTI, at 207.4 per 1000 child-years (95% CI: 149.0-279.5). Younger age group, place of living and low educational level of caregivers were associated with developing RSV-LRTI. Clinical manifestations had low levels of agreement with hypoxaemia as measured by pulse oximeter.

Conclusion: The highest burden of RSV was observed in young infants aged 3-5 months, whereas the burden was also high in those aged 12-20 months. Future vaccination strategies should consider the protection of older children, especially those aged one year, as well as young infants.
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http://dx.doi.org/10.1111/irv.12639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586181PMC
July 2019

Understanding user requirements to improve adoption of influenza diagnostics in clinical care within Metro Manila.

Health Sci Rep 2018 Sep 7;1(9):e75. Epub 2018 Aug 7.

Research Institute for Tropical Medicine Department of Health Metro Manila Philippines.

Background And Aim: Influenza diagnostics play a critical role informing in clinical management decisions and defining the global epidemiology of the disease to support public health responses. Use of influenza diagnostics within most low-income and middle-income countries remains limited, including in the Philippines, where they are currently used only for epidemiologic surveillance. The aim of this study was to define key considerations, including product characteristics, which may influence future adoption, uptake, and integration of influenza diagnostics into public and private clinical settings in this emerging Asian market.

Methods: Our study was conducted using a convenience sample of public and private hospital laboratories in Metro Manila. A usability assessment was conducted that included interviews with decision-makers and direct observation of laboratory end users using 2 platforms representative of emerging diagnostic products: (1) a point-of-care antigen-based rapid immunoassay diagnostic test paired with a reader and (2) a molecular diagnostic platform intended for decentralized use. Data were analyzed to assess user errors and device failure modes with each platform and to determine key considerations related to product adoption and uptake.

Results: The most difficult test step for most users on both platforms involved sample preparation. When deciding to adopt a new test, priority product attributes include performance, potential volume of demand from clinicians, equipment cost, and ease of use. Demand for new tests is likely going to be driven by clinicians, and policies and guidelines will be needed to support the introduction of new products.

Conclusion: Adoption of influenza diagnostics in Metro Manila is feasible but will require affordable products capable of satisfying needs for use in both epidemiologic surveillance and clinical management.
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http://dx.doi.org/10.1002/hsr2.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266513PMC
September 2018

Complete Genome Sequences of 12 Human Respiratory Syncytial Virus () Strains Detected in Children with Repeated Subgroup B Infections in the Philippines.

Microbiol Resour Announc 2018 Dec 6;7(22). Epub 2018 Dec 6.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Complete genome sequences were determined for 12 human respiratory syncytial virus strains collected from nasopharyngeal samples obtained from children with repeated subgroup B infections. Eight common amino acid polymorphisms in the G, F, and L proteins were identified between the viruses detected in initial and subsequent infections.
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http://dx.doi.org/10.1128/MRA.01017-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284083PMC
December 2018

Detection of Subgenotype IA and IIIA Hepatitis A Viruses in Rivers Flowing through Metro Manila, the Philippines.

Jpn J Infect Dis 2019 Jan 31;72(1):53-55. Epub 2018 Aug 31.

Department of Virology II, National Institute of Infectious Diseases.

Hepatitis A virus (HAV) is a common infectious etiology of acute hepatitis worldwide. The Philippines remains highly endemic for hepatitis A, but there is still a lack of information about HAV in the country. To evaluate the HAV contamination in environmental water in the Philippines, we conducted the detection and genetic analyses of HAV RNA in samples from river water. Twelve water samples were collected at 6 sampling sites of 3 rivers in Metro Manila, in both the dry and wet seasons in 2012 and 2013. The HAV RNA was detected in all the 6 samples collected in the dry season, and in one sample from the wet season. Phylogenetic analysis confirmed that the HAV strains detected in the river water included multiple sequences belonging to subgenotypes IA and IIIA. This indicates that at least 2 genotypes of the HAV strains are circulating in the environment in the Philippines, posing a risk of HAV infection to not only residents, but also tourists, especially in the dry season.
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http://dx.doi.org/10.7883/yoken.JJID.2018.148DOI Listing
January 2019

Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines.

J Infect Dis 2018 08;218(7):1045-1053

Department of Virology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.

Background: Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes.

Methods: We conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections.

Results: We examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein.

Conclusions: Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.
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http://dx.doi.org/10.1093/infdis/jiy256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107742PMC
August 2018

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

Lancet Glob Health 2017 10;5(10):e984-e991

Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Netherlands; ReSViNET Respiratory Syncytial Virus Network, Utrecht, Netherlands. Electronic address:

Background: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data.

Methods: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables.

Findings: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries.

Interpretation: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(17)30344-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599304PMC
October 2017

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

Authors:
Ting Shi David A McAllister Katherine L O'Brien Eric A F Simoes Shabir A Madhi Bradford D Gessner Fernando P Polack Evelyn Balsells Sozinho Acacio Claudia Aguayo Issifou Alassani Asad Ali Martin Antonio Shally Awasthi Juliet O Awori Eduardo Azziz-Baumgartner Henry C Baggett Vicky L Baillie Angel Balmaseda Alfredo Barahona Sudha Basnet Quique Bassat Wilma Basualdo Godfrey Bigogo Louis Bont Robert F Breiman W Abdullah Brooks Shobha Broor Nigel Bruce Dana Bruden Philippe Buchy Stuart Campbell Phyllis Carosone-Link Mandeep Chadha James Chipeta Monidarin Chou Wilfrido Clara Cheryl Cohen Elizabeth de Cuellar Duc-Anh Dang Budragchaagiin Dash-Yandag Maria Deloria-Knoll Mukesh Dherani Tekchheng Eap Bernard E Ebruke Marcela Echavarria Carla Cecília de Freitas Lázaro Emediato Rodrigo A Fasce Daniel R Feikin Luzhao Feng Angela Gentile Aubree Gordon Doli Goswami Sophie Goyet Michelle Groome Natasha Halasa Siddhivinayak Hirve Nusrat Homaira Stephen R C Howie Jorge Jara Imane Jroundi Cissy B Kartasasmita Najwa Khuri-Bulos Karen L Kotloff Anand Krishnan Romina Libster Olga Lopez Marilla G Lucero Florencia Lucion Socorro P Lupisan Debora N Marcone John P McCracken Mario Mejia Jennifer C Moisi Joel M Montgomery David P Moore Cinta Moraleda Jocelyn Moyes Patrick Munywoki Kuswandewi Mutyara Mark P Nicol D James Nokes Pagbajabyn Nymadawa Maria Tereza da Costa Oliveira Histoshi Oshitani Nitin Pandey Gláucia Paranhos-Baccalà Lia N Phillips Valentina Sanchez Picot Mustafizur Rahman Mala Rakoto-Andrianarivelo Zeba A Rasmussen Barbara A Rath Annick Robinson Candice Romero Graciela Russomando Vahid Salimi Pongpun Sawatwong Nienke Scheltema Brunhilde Schweiger J Anthony G Scott Phil Seidenberg Kunling Shen Rosalyn Singleton Viviana Sotomayor Tor A Strand Agustinus Sutanto Mariam Sylla Milagritos D Tapia Somsak Thamthitiwat Elizabeth D Thomas Rafal Tokarz Claudia Turner Marietjie Venter Sunthareeya Waicharoen Jianwei Wang Wanitda Watthanaworawit Lay-Myint Yoshida Hongjie Yu Heather J Zar Harry Campbell Harish Nair

Lancet 2017 Sep 7;390(10098):946-958. Epub 2017 Jul 7.

Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK; Public Health Foundation of India, New Delhi, India. Electronic address:

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.

Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.

Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.

Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.

Funding: The Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(17)30938-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592248PMC
September 2017

Estimates of influenza and respiratory syncytial virus incidences with fraction modeling approach in Baguio City, the Philippines, 2012-2014.

Influenza Other Respir Viruses 2017 07 3;11(4):311-318. Epub 2017 May 3.

Department of Epidemiology and Biostatistics, Department of Health, Research Institute for Tropical Medicine, Manila, Philippines.

Background: Estimation of the incidences of influenza and respiratory syncytial virus (RSV) infection is important for disease control. Previous estimate in the city showed a substantial burden of influenza in both outpatients and inpatients while it did not account for individuals who do not seek medical attention nor RSV.

Patients/methods: A total of 17 674 influenza-like illness (ILI) and 13 242 severe acute respiratory illness (SARI) cases were recruited, and samples were collected from 6267 and 2962 of ILI and SARI cases, respectively. RT-PCR assays were performed to detect influenza and RSV in the samples. A health-seeking behavior survey was conducted from February 2014 to April 2014 to estimate the fraction of infected individuals who did not seek medical attention between rainy and dry season.

Results: Average influenza and RSV incidence rates in outpatients were 1.6 and 1.4 per 1000 individuals, respectively, and the highest incidence rate for both viruses was found in the of 6-23 month age group. Average influenza and RSV hospitalization incidence rates were 1.7 and 1.9 per 1000 individuals, respectively. Further, we estimated that the incidence rates of influenza and RSV in individuals who did not seek medical attention were threefold and 1.6-fold those in the medically attended population.

Conclusions: Respiratory syncytial virus and influenza pose a substantial disease burden, particularly in hospitalized cases. The implementation of either a community-based approach or an enhanced surveillance system in combination with a community survey will allow a better understanding of the disease burdens of RSV and influenza in the Philippines.
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http://dx.doi.org/10.1111/irv.12453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485869PMC
July 2017

Laboratory Diagnosis for Outbreak-Prone Infectious Diseases after Typhoon Yolanda (Haiyan), Philippines.

PLoS Curr 2016 Oct 21;8. Epub 2016 Oct 21.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Introduction: Typhoon Yolanda (Haiyan) hit the central part of the Philippines on November 8, 2013. To identify possible outbreaks of communicable diseases after the typhoon, nasopharyngeal swabs, stool and blood samples were collected from patients who visited the Eastern Visayas Regional Medical Center due to acute respiratory infection (ARI), acute gastroenteritis (AGE) or other febrile illness (OFI) including suspected dengue fever, between November 28, 2013 and February 5, 2014.   Methods: Samples were tested on-site for selected pathogens using rapid diagnostic tests. Confirmation and further analysis were conducted at the Research Institute for Tropical Medicine (RITM) in Manila using polymerase chain reaction (PCR) and sequencing. Residues of the rapid diagnostic tests and samples collected in the filter papers (FTATM card) were transported to Manila under suboptimal conditions. PCR results were compared between the kit residues and the filter papers.   Results: A total of 185 samples were collected. Of these, 128 cases were ARI, 17 cases were AGE and 40 cases were OFI. For nasopharyngeal swab samples, detection rates for enterovirus and rhinovirus residues were higher than the filter papers. For stool samples, rotavirus positive rate for the filter paper was higher than the kit residues. We also managed to obtain the sequence data from some of the kit residues and filter papers.   Discussion: Our results confirmed the importance of PCR for the laboratory diagnosis of infectious diseases in post-disaster situations when  diagnostic options are limited.
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http://dx.doi.org/10.1371/currents.dis.9c3cb7b01ec2d04eef2406dbe03d253dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104685PMC
October 2016

Distance to health services modifies the effect of an 11-valent pneumococcal vaccine on pneumonia risk among children less than 2 years of age in Bohol, Philippines.

Int J Epidemiol 2017 04;46(2):706-716

Children's Hospital of Colorado, University of Colorado, Denver, CO, USA.

Background: Both vaccine trials and surveillance studies typically use passive surveillance systems to monitor study outcomes, which may lead to under-reporting of study outcomes in areas with poor access to care. This detection bias can have an adverse effect on conventional estimates of pneumonia risk derived from vaccine trials.

Methods: We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent pneumococcal vaccine (PCV) among children less than 2 years of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographical information system. The study was conducted using 11 729 children who received three doses of any study vaccine (PCV11) or placebo. Multivariate Cox proportional hazards models were used to examine major risk factors for pneumonia diagnosis and the relationship between distance to Bohol Regional Hospital (BRH) and vaccination with PCV with risk for pneumonia diagnosis.

Results: There was a significant interaction effect between distance from BRH and vaccination with PCV11 on pneumonia risk. Among children living 12 km from BRH, vaccination with PCV11 was associated with a decreased hazard ratio for radiographic pneumonia, compared with vaccination with the study placebo [0.57, 95% confidence interval (CI) 0.37-0.86). However, for children living 1 km from BRH, there was little difference in risk of radiographic pneumonia diagnosis between children vaccinated with PCV11 and those given the study placebo.

Conclusion: Children living close to BRH had no documented reduction in the primary study outcome from PCV11, whereas those at greater distance experienced a substantial reduction. Because of detection bias caused by distance to BRH, in spatial analysis of vaccine trial results it may be necessary to adjust estimates of pneumonia risk and vaccine efficacy. Failure to consider the geographical dimension of trials may lead to underestimates of efficacy which might influence public health planning efforts.
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http://dx.doi.org/10.1093/ije/dyw217DOI Listing
April 2017

WU and KI polyomavirus infections in Filipino children with lower respiratory tract disease.

J Clin Virol 2016 09 26;82:112-118. Epub 2016 Jul 26.

University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA; Center for Global Health, Colorado School of Public Health, Aurora, CO, USA. Electronic address:

Background: WU and KI are human polyomaviruses initially detected in the respiratory tract, whose clinical significance remains uncertain.

Objectives: To determine the epidemiology, viral load and clinical characteristics of WU and KI polyomaviruses.

Study Design: We tested respiratory specimens collected during a randomized, placebo-controlled pneumococcal conjugate vaccine trial and related epidemiological study in the Philippines. We analyzed 1077 nasal washes from patients aged 6 weeks to 5 years who developed lower respiratory tract illness using quantitative real-time PCR for WU and KI. We collected data regarding presenting symptoms, signs, radiographic findings, laboratory data and coinfection.

Results: The prevalence and co-infection rates for WU were 5.3% and 74% respectively and 4.2% and 84% respectively for KI. Higher KI viral loads were observed in patients with severe or very severe pneumonia, those presenting with chest indrawing, hypoxia without wheeze, convulsions, and with KI monoinfection compared with co-infection. There was no significant association between viral load and clinical presentation for WU.

Conclusions: These findings suggest a potential pathogenic role for KI, and that there is an association between KI viral load and illness severity.
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http://dx.doi.org/10.1016/j.jcv.2016.07.013DOI Listing
September 2016

Molecular detection and characterization of sapovirus in hospitalized children with acute gastroenteritis in the Philippines.

J Clin Virol 2015 Jul 6;68:83-8. Epub 2015 May 6.

Department of Virology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

Background: Human sapovirus (SaV) is a causative agent of acute gastroenteritis. Recently, SaV detection has been increasing worldwide due to the emerging SaV genotype I.2. However, SaV infection has not been reported in the Philippines.

Objectives: To evaluate the prevalence and genetic diversity of SaV in hospitalized children aged less than 5 years with acute gastroenteritis.

Study Design: Stool samples were collected from children with acute gastroenteritis at three hospitals in the Philippines from June 2012 to August 2013. SaV was detected by reverse transcription real-time PCR, and the polymerase and capsid gene sequences were analyzed. Full genome sequencing and recombination analysis were performed on possible recombinant viruses.

Results: SaV was detected in 7.0% of the tested stool samples (29/417). In 10 SaV-positive cases, other viruses were also detected, including rotavirus (n=6), norovirus (n=2), and human astrovirus (n=2). Four known SaV genotypes (GI.1 [7], GI.2 [2], GII.1 [12], and GV [2]) and one novel recombinant (n=3) were identified by polymerase and capsid gene sequence analysis. Full genome sequencing revealed that the 5' nontranslated region (NTR) and nonstructural protein region of the novel recombinant were closely related to the GII.1 Bristol/98/UK variant, whereas the structural protein region and 3' NTR were closely related to the GII.4 Kumamoto6/Mar2003/JPN variant.

Discussion And Conclusions: SaV was regularly detected in hospitalized children due to acute gastroenteritis during the study period. A novel recombinant, SaV GII.1/GII.4, was identified in three cases at two different study sites.
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http://dx.doi.org/10.1016/j.jcv.2015.05.001DOI Listing
July 2015

Molecular epidemiology of Bordetella pertussis in the Philippines in 2012-2014.

Int J Infect Dis 2015 Jun 8;35:24-6. Epub 2015 Apr 8.

Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address:

Objectives: The present study was designed to determine the genotypes of circulating Bordetella pertussis in the Philippines by direct molecular typing of clinical specimens.

Methods: Nasopharyngeal swabs (NPSs) were collected from 50 children hospitalized with pertussis in three hospitals during 2012-2014. Multilocus variable-number tandem repeat analysis (MLVA) was performed on the DNA extracts from NPSs. B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter, ptxP, were also investigated by DNA sequence-based typing.

Results: Twenty-six DNA extracts yielded a complete MLVA profile, which were sorted into 10 MLVA types. MLVA type 34 (MT34), which is rare in Australia, Europe, Japan, and the USA, was the predominant strain (50%). Seven MTs (MT29, MT32, MT33, and MT283-286, total 42%) were single-locus variants of MT34, while two (MT141 and MT287, total 8%) were double-locus variants of MT34. All MTs had the combination of virulence-associated allelic genes, ptxP1-ptxA1-prn1-fim3A.

Conclusions: The B. pertussis population in the Philippines comprises genetically related strains. These strains are markedly different from those found in patients from other countries where acellular pertussis vaccines are used. The differences in vaccine types between these other countries and the Philippines, where the whole-cell vaccine is still used, may select for distinct populations of B. pertussis.
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http://dx.doi.org/10.1016/j.ijid.2015.04.001DOI Listing
June 2015

Molecular epidemiology of enterovirus D68 from 2013 to 2014 in Philippines.

J Clin Microbiol 2015 Mar 7;53(3):1015-8. Epub 2015 Jan 7.

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan

Enterovirus D68 (EV-D68) has been recognized as an important cause of acute respiratory infections. Here we report the molecular epidemiology of EV-D68 in Philippines from 2013 to 2014; we found cases in areas affected by Typhoon Haiyan and found new strains in the country.
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http://dx.doi.org/10.1128/JCM.03362-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390660PMC
March 2015

Isolation and characterization of influenza C viruses in the Philippines and Japan.

J Clin Microbiol 2015 Mar 31;53(3):847-58. Epub 2014 Dec 31.

Department of Virology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, Japan

From November 2009 to December 2013 in the Philippines, 15 influenza C viruses were isolated, using MDCK cells, from specimens obtained from children with severe pneumonia and influenza-like illness (ILI). This is the first report of influenza C virus isolation in the Philippines. In addition, from January 2008 to December 2013, 7 influenza C viruses were isolated from specimens that were obtained from children with acute respiratory illness (ARI) in Sendai city, Japan. Antigenic analysis with monoclonal antibodies to the hemagglutinin-esterase (HE) glycoprotein showed that 19 strains (12 from the Philippines and 7 from Japan) were similar to the influenza C virus reference strain C/Sao Paulo/378/82 (SP82). Phylogenetic analysis of the HE gene showed that the strains from the Philippines and Japan formed distinct clusters within an SP82-related lineage. The clusters that included the Philippine and Japanese strains were shown to have diverged from a common ancestor around 1993. In addition, phylogenetic analysis of the internal genes showed that all strains isolated in the Philippines and Japan had emerged through reassortment events. The composition of the internal genes of the Philippine strains was different from that of the Japanese strains, although all strains were classified into an SP82-related lineage by HE gene sequence analysis. These observations suggest that the influenza C viruses analyzed here had emerged through different reassortment events; however, the time and place at which the reassortment events occurred were not determined.
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http://dx.doi.org/10.1128/JCM.02628-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390655PMC
March 2015

Molecular detection of hepatitis E virus in rivers in the Philippines.

Am J Trop Med Hyg 2014 Apr 3;90(4):764-6. Epub 2014 Mar 3.

Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-Murayama, Tokyo 208-0011, Japan; Department of Clinical Laboratory, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China; Department of Virology, Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan; RITM-Tohoku Collaborating Research Center on Emerging and Re-Emerging Infectious Diseases, Filinvest Corporate City, Alabang, Muntinlupa City 1781, the Philippines; Research Institute for Tropical Medicine, Department of Health Compound, FILINVEST Corporate City, Alabang, Muntinlupa City 1781, the Philippines.

To understand the hepatitis E virus (HEV)-pollution status in the environment in the Philippines, a total of 12 water samples were collected from rivers in Manila City for detection of HEV RNA. Three of 12 samples were positive for HEV RNA indicating that HEV is circulating in the Philippines. Phylogenetic analysis classified all of the HEV sequences into genotype 3.
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http://dx.doi.org/10.4269/ajtmh.13-0562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973527PMC
April 2014

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

Proc Natl Acad Sci U S A 2014 Mar 18;111(9):3520-5. Epub 2014 Feb 18.

Department of Geography and Institute of Behavioral Sciences, University of Colorado Boulder, Boulder, CO 80309.

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.
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http://dx.doi.org/10.1073/pnas.1313748111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948245PMC
March 2014

Molecular characteristics of extended-spectrum β-lactamases in clinical isolates of Enterobacteriaceae from the Philippines.

Acta Trop 2011 Oct-Nov;120(1-2):140-5. Epub 2011 Jul 28.

Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai 980-8574, Japan.

β-Lactamases, including extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases, are major resistance mechanisms of Enterobacteriaceae. Emergence of plasmid-mediated quinolone resistance (PMQR) determinants in ESBL-producing isolates poses a global threat. The molecular characterisitcs of ESBL and PMQR determinants in the Philippines are not well characterized. In this study, we investigated ESBLs and AmpC β-lactamases in clinical isolates of Enterobacteriaceae from the Philippines, and analyzed the association between ESBL and PMQR genes. A total of 91 amoxicilin non-susceptible Enterobacteriaceae were collected at the Research Institute for Tropical Medicine of the Philippines from 2006 to 2008. AmpC- or ESBL-producing isolates were screened by detecting a zone diameter for cefoxitin ≤ 14 mm or cefpodoxime ≤ 20 mm, respectively. Possible ESBL-producing strains were assessed by the ESBL confirmation test of the Clinical and Laboratory Standards Institute. PCR and sequencing were performed to detect the ESBL and PMQR genes. The number of ESBL-producers and AmpC-producers confirmed phenotypically was 17 (18.7%) and 61 (67.0%), respectively. Of 17 phenotypic ESBL-producers, 14 isolates had ESBL genes, including 6 of Escherichia coli, 3 of Enterobacter cloacae, 2 of Enterobacter aerogenes, 2 of Klebsiella pneumoniae, and 1 of Klebsiella ozaenae. Among these isolates, there were 13, 4, and 12 with bla(CTX-M), bla(SHV), and bla(TEM), respectively. Of the bla(CTX-M)-positive isolates, bla(CTX-M-15) shows the highest prevalence, followed by bla(CTX-M-3) and bla(CTX-M-14). Of 14 ESBL-producers identified by PCR, 4, 6, and 7 isolates were positive for qnrB, qnrS, and aac(6')-Ib-cr, respectively. The frequency of aac(6')-Ib-cr positivity was significantly higher among CTX-M-15-producing isolates. Thus, we identified bla(CTX-M), aac(6')-Ib-cr, and qnr in ESBL-producing Enterobacteriaceae from the Philippines, and revealed a significant association between bla(CTX-M-15) and aac(6')-Ib-cr. Local epidemiological data are important for implementing appropriate antimicrobial therapy and effective infection control measures. Continuous monitoring of antimicrobial resistance genes in the Philippines will be required.
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http://dx.doi.org/10.1016/j.actatropica.2011.07.007DOI Listing
March 2012

Detection of novel respiratory viruses from influenza-like illness in the Philippines.

J Med Virol 2010 May;82(6):1071-4

Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Several novel viruses have been recently identified in respiratory samples. However, the epidemiology of these viruses in tropical countries remains unclear. The aim of the present study was to provide an overview of the epidemiology of novel respiratory viruses, including human metapneumovirus, human bocavirus, new subtypes of human coronavirus (NL63 and HKU1), KI virus, WU virus, and Melaka virus in the Philippines, a tropical country. Nasopharyngeal aspirates from 465 patients with influenza-like illness were collected in 2006 and 2007. Reverse transcription polymerase chain reaction (RT-PCR) and PCR were performed to detect viruses from culture-negative specimens. Human metapneumovirus, human bocavirus, human coronavirus HKU1, KI virus, and WU virus were detected for the first time in the Philippines; Melaka virus was not found.
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http://dx.doi.org/10.1002/jmv.21763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166497PMC
May 2010

Pneumonia among young infants in rural Southeast Asia (Bohol Island, Philippines).

Trop Med Int Health 2009 Dec 21;14(12):1457-66. Epub 2009 Oct 21.

Clinical Research Division, Research Institute for Tropical Medicine (RITM), Manila, Philippines.

Objective: To develop a clinical algorithm that can be used to identify pneumonia deaths in young infants in developing countries and estimate the disease burden in this population.

Patients And Methods: Infants younger than 60 days hospitalized with signs of severe pneumonia who underwent clinical, microbiologic and radiological evaluation were the subjects. Stepwise logistic regression and subtractive iterative process were used to derive the algorithm.

Results: Three-hundred and one infants had either clinical or radiographic pneumonia. The case fatality rate for 185 infants with radiographic pneumonia was 21%vs. 5% for clinical pneumonia. Age below 7 days was associated with an increased risk of dying. Among 7- to 59-day-old infants, poor feeding, cyanosis and absence of crackles were predictors of death from pneumonia. Using logistic regression, an algorithm consisting of any one of three clinical signs (cyanosis, poor feeding and abnormally sleepy) was developed in infants aged 7-59 days; 80% of deaths and 50% of those with radiographic pneumonia have at least one of these signs. It performed better than both the WHO case management algorithm and the IMCI algorithm.

Conclusion: Radiographic pneumonia is a common and serious infection among infants below 2 months old in the Philippines. Cyanosis, poor feeding and abnormal sleepiness are simple signs that can be used by health workers to identify seriously ill infants who are most likely to die from pneumonia.
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http://dx.doi.org/10.1111/j.1365-3156.2009.02398.xDOI Listing
December 2009

Serious community-acquired paediatric infections in rural Asia (Bohol Island, Philippines): bacterial meningitis in children less than 5 years of age.

Scand J Infect Dis 2007 21;39(11-12):983-9. Epub 2007 Jun 21.

From the Celestino Gallares Memorial Hospital, Bohol, Philippines.

This paper describes the clinical profile and aetiology of bacterial meningitis in infants and children less than 5 y old admitted to a rural general hospital in the Philippines. A total of 989 infants and children 0-59 months old with suspected meningitis using a standardized guideline based on clinical signs and symptoms were prospectively enrolled from April 1994 to May 2000. Blood and CSF were drawn on admission for culture, antigen testing and cell count. All had blood cultures and 623 (63%) had CSF samples. Bacterial aetiology was found in 54 (5%). The most common bacterial pathogens were H. influenzae type b (Hib) (20, 37%) and S. pneumoniae (Pnc) (10, 18%). All of the Hib infections and 8 (80%) Pnc infections were in infants less than 1 y old. 12 (22%) of the subjects with bacterial meningitis died. All strains of S. pneumoniae and H. influenzae were sensitive to chloramphenicol, cotrimoxazole and ampicillin. In conclusion, S. pneumoniae and H. influenzae type b are the most common aetiological agents of bacterial meningitis in a rural area in the Philippines, and occur especially in infants less than 1 y old. Aetiological agents were susceptible to the currently recommended antimicrobial agents.
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http://dx.doi.org/10.1080/00365540701466157DOI Listing
March 2008

Central nervous system infection is an important cause of death in underfives hospitalised with World Health Organization (WHO) defined severe and very severe pneumonia.

Vaccine 2007 Mar 20;25(13):2437-44. Epub 2006 Sep 20.

Research Institute for Tropical Medicine, Philippines.

Over 6 years, 1667 children aged 2-59 months admitted for pneumonia [1287 severe and 380 very severe] were studied. The case fatality rate (CFR) in children with severe pneumonia was 2.1% and 14.3% with CNS infection, with very severe pneumonia the CFR was 18.9%, 10.4% in those with hypoxemia and 43.6% with CNS infection. High CFRs were associated with CNS infection and inability to drink/cyanosis. The appropriate management of children with very severe pneumonia should include cerebrospinal fluid examination, oxygen monitoring and possibly ventilated support, suggesting that these are minimal standards of care at the district hospital.
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http://dx.doi.org/10.1016/j.vaccine.2006.09.017DOI Listing
March 2007