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.

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.

Laboratory-confirmed Dengue in Children in Three Regional Hospitals in the Philippines in 2009-2010.

BACKGROUND: The burden of dengue is high in the Philippines but the prevalence of confirmed cases is unknown, and the disease is subject to underreporting because surveillance of suspected cases is passive. We conducted a prospective epidemiological study to estimate the proportion of laboratory-confirmed dengue among clinically suspected hospitalized cases in the pediatric wards of 3 regional hospitals in the Philippines and to describe the clinical and laboratory features, age distributions, case fatality rates and serotype distributions of these hospitalized cases. METHODS: Patients ≤18 years and hospitalized for suspected dengue were included if they had an axillary temperature ≥38°C for 2-7 days and 2 or more dengue-associated symptoms. Dengue infection was confirmed in acute blood samples by serotype-specific reverse transcription-polymerase chain reaction and IgM immunoassay. RESULTS: We confirmed dengue infection in 1809 (86.1%) cases of 2103 suspected cases between November 2009 and November 2010. The 6- to 10-year-old age group had the highest proportion of cases overall (36.7%). Fever, anorexia, myalgia, abdominal pain and headache were the most common symptoms at admission. Hemorrhagic manifestations, signs of plasma leakage, thrombocytopenia and leucopenia were all significantly more common in confirmed than in nonconfirmed cases. Most cases (76.5%) developed dengue hemorrhagic fever or dengue shock syndrome, and the overall case fatality rate was 0.94%. Distributions of all 4 virus serotypes varied at each hospital. CONCLUSIONS: The clinical burden of pediatric dengue continues to be substantial in the Philippines. Most hospitalized cases of suspected pediatric dengue can be laboratory confirmed and most develop severe disease.

HLA-A*33:01 as protective allele for severe dengue in a population of Filipino children.

Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection.

Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines.

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and ß- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.