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Enterovirus 68 (EV68) is a rare enterovirus associated with respiratory illness that, unlike other enteroviruses, has been identified only from respiratory specimens. We identified EV68 from respiratory specimens of children hospitalized with a diagnosis of severe pneumonia in Leyte, Republic of the Philippines. Twenty-one samples showed high similarity with EV68 by sequencing of 5' nontranslated region; 17 of these samples were confirmed as EV68 by sequencing of viral protein 1 capsid coding region. Most previously reported EV68 cases had been identified as sporadic cases. All 21 patients we identified had severe illness, and 2 died, possibly the first reported fatal cases associated with EV68 infection. Our study suggests that EV68 may be a possible causative agent of severe respiratory illnesses. [ABSTRACT FROM AUTHOR]

Abstract Background Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. Methods The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. Result Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. Conclusion Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.

Background: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality among adults worldwide. However, the distribution of the etiology of CAP varies from one country to another, with limited data from rural areas., Methods: A prospective hospital-based study on adult CAP was conducted in Leyte, Central Philippines from May 2010 to May 2012. Blood, sputum, and nasopharyngeal samples obtained from patients were used to identify pathogens using standard microbiological culture methods and PCR., Results: Of the 535 patients enrolled, 38% were younger than 50 years old. More than half of the patients had an underlying disease, including pulmonary tuberculosis (22%). The detection rate was higher for bacteria (40%) than viruses (13%). Haemophilus influenzae (12%) was the most commonly detected bacterium and influenza virus (5%) was the most commonly detected virus. The proportion of CAP patients with Mycobacterium tuberculosis infection was higher in the younger age group than in the older age group. Among CAP patients, 14% died during hospitalization, and drowsiness on admission and SpO 2 <90% were independent risk factors for mortality., Conclusions: Bacterial infections contribute substantially to the number of hospitalizations among CAP patients in rural Philippines. This study also highlights the importance of treatment of tuberculosis in reducing the burden of adult CAP in the country., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human adenovirus (HAdV) serotype 7 is an important etiological agent of severe childhood pneumonia. The aim of this study was to define the role of HAdV7 and to describe its clinical and molecular epidemiological characteristics in the Philippines in 2011. HAdVs were detected by viral culture, and a partial region of hexon gene was sequenced. A total of 700 patients were enrolled, of which 22 (3.1%) died. Nine (1.3%) HAdV cases were confirmed, of which 7 were positive for HAdV7, 1 for HAdV3, and 1 for HAdV5. Among the 9 HAdV-positive cases, 4 (44%) with HAdV7 died. Molecular analysis revealed that all HAdV7 isolates were closely related to genome type h strains. This study demonstrated the significance of HAdV7 as an etiological agent of severe pediatric pneumonia with a high fatality rate. Hence, continuous monitoring is required to define the clinical and public health significance of HAdV7 infection.

Background: Detection of Enterovirus 68 (EV68) has recently been increased. However, underlying evolutionary mechanism of this increasing trend is not fully understood., Methods: Nasopharyngeal swabs were collected from 5,240 patients with acute respiratory infections in the Philippines from June 2009 to December 2011. EV68 was detected by polymerase chain reaction (PCR) targeting for 5' untranslated region (5'UTR), viral protein 1 (VP1), and VP4/VP2. Phylogenetic trees were generated using the obtained sequences., Results: Of the 5,240 tested samples, 12 EV68 positive cases were detected between August and December in 2011 (detection rate, 0.23%). The detection rate was higher among inpatients than outpatients (p<0.0001). Among VP1 sequences detected from 7 patients in 2011, 5 in lineage 2 were diverged from those detected in the Philippines in 2008, however, 2 in lineage 3 were not diverged from strains detected in the Philippines in 2008 but closely associated with strains detected in the United States. Combined with our previous report, EV68 occurrences were observed twice in the Philippines within the last four years., Conclusions: EV68 detections might be occurring in cyclic patterns, and viruses might have been maintained in the community while some strains might have been newly introduced.

Human rhinovirus (HRV) C was recently identified as the third species of HRV using a molecular technique. Infections caused by previously identified HRVs (A and B) are thought to be limited to the respiratory tract; however, pathogenesis of HRVC is still largely unknown. A total of 816 nasopharyngeal swabs from hospitalized children with severe respiratory infections in the Philippines (May 2008-May 2009) were tested for HRV by reverse transcription polymerase chain reaction (RT-PCR), and 243 samples (29.8%) were positive for HRV. Among these patients, serum samples were also tested to determine whether specific HRV species were associated with viremia. Only 30 serum samples (12.3%) were positive for HRV. However, the HRV positive rates were different among HRV species, 3% (4/135) for HRVA, 0% (0/25) for HRVB, and 31% (26/83) for HRVC, and were the highest on 2 days after the onset of symptoms. These results suggest that HRVC may have a different pathogenicity and can more commonly cause viremia than HRVA and HRVB. Serum positive rates for HRV are affected by age, i.e., higher positive rates for those aged 1 year or more. HRVC that were detected from serum exhibited the same level of sequence diversity as those positive only for nasopharyngeal samples in phylogenetic analysis. However, all HRVA which were detected from serum were clustered in a monophyletic clade based on their 5' non-coding region (NCR) sequences, which is closely related with a certain HRVC genotype (A2) in 5'-NCR. This finding suggests that the 5'NCR region may be associated with viremia.

Objectives: The value of measurements of serum C-reactive protein (CRP) in differentiating central nervous system (CNS) infections of varying etiologies in the Philippines was investigated., Methods: A wide array of bacteriologic and virologic methods as well as computed tomography, typical clinical presentation, and autopsy were used for etiologic diagnosis., Results: Among 103 patients with CNS infection, etiology was identified in 60 (58%) cases. Bacteria were found in 19 (including 7 Streptococcus pneumoniae, 5 Haemophilus influenzae, 3 Neisseria meningitidis), tuberculosis in 4, viruses in 38 (including 20 coxsackievirus, 8 measles, 4 adenovirus, and 4 poliovirus infections), and brain abscess in 3 patients. C-reactive protein was elevated on admission in all 18 cases of bacterial meningitis tested, exceeding 50 mg/L in 17 (94%), and was not affected by prior antibacterial treatment. The mean CRP was significantly higher in the bacterial group than in the viral group (207 +/- 111 mg/L vs. 39 +/- 34 mg/L; P < 0.001). In the viral group one third had CRP above 50 mg/L. In patients with tuberculous meningitis, brain abscess, or cryptococcal meningitis, CRP was moderately to highly elevated., Conclusions: In the presence of a normal CRP concentration (below 10 mg/mL) acute bacterial meningitis is excluded even in a developing country setting and antimicrobial therapy is not warranted.

Serum antibody responses to three Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccine (PRP-OMP, PRP-T, and HbOC) were evaluated in 174 Philippine infants after a primary vaccination series. Children were randomized to receive one of the Hib vaccines (Hib groups) or into a control group. Vaccination was carried out at six, 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule. Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects. Anti-Hib concentrations were determined by the Farr-type radioimmunoassay. There were no significant differences (P = 0.3626) in the prevaccination anti-Hib geometric mean concentration (GMC) among the three Hib groups. Differences in the GMC after the primary series of three doses were significant (P < 0.0001); GMC was highest for PRP-T (6.62 micrograms/ml), followed by HbOC (1.9 micrograms/ml), then PRP-OMP (1.06 micrograms/ml), and lowest for the control group (0.11 microgram/ml). We conclude that all three Hib conjugate vaccines (PRP-T, HbOC, and PRP-OMP) were immunogenic after three primary doses among Philippine infants.