Objective: The clinical presentation, outcome, and risk factors for mortality in children with Fever of Unknown Origin (FUO) were determined. Methods: Medical records of pediatric patients admitted for FUO from January 2009 to December 2013 were reviewed. Clinical manifestations, physical exam findings, diagnostic work-ups and final diagnosis were determined, as well as the relationship between final diagnosis and risk for mortality. Results: Fifty-seven patients with FUO were included. Weight loss, cough, colds, and rashes were common symptoms while pallor, lymphadenopathies, and hepatomegaly were common physical exam findings. All patients underwent Phase I evaluation for FUO, while 73.7% underwent further diagnostic tests. A specific etiology was established in 96.5% of cases: infectious, 43.9%, connective tissue disease, 38.6%, and hematologic/oncologic, 14%. Two cases remained to have no specific diagnosis. Majority of patients had a benign course and were discharged improved (84.2%). The mortality rate is 15.8% and was not associated with any disease category (p-value 0.204). Conclusion FUO in children occurs across all age groups. Its clinical presentations are varied and non-specific and common signs and symptoms are pallor, lymphadenopathies, weight loss, cough, colds. and joints pains. Infection is the most common cause of FUO in children, followed by connective tissue diseases and hematologic and oncologic diseases. The mortality rate from FUO is 15.8%.
Fever of Unknown Origin

RATIONALE: Among the first line antituberculosis (anti-TB) drugs, the major drug incriminated in the development of hepatotoxicity is isoniazid (INH). The human N-acetyl transferase2 (NAT2) gene is mainly responsible for INH metabolism. This gene exhibits a hereditarily determined polymorphism. There is presently no study on the predominant NAT2 genotype among Filipinos. There are also no Filipino studies on the incidence of hepatitis and other adverse effects of first line anti-TB drugs.

OBJECTIVES: To determine the predominant NAT2 genotype and its association with the development of hepatitis among Filipino children given first line anti-TB drugs (INH, rifampicin and pyrazinamide) and to determine the incidence of hepatitis and other serious adverse reactions to these drugs.

STUDY DESIGN: Prospective cohort study

SETTING: Tertiary government hospital in Metro Manila

STUDY POPULATION: Children on to 18 years old with pulmonary tuberculosis and normal liver function test at baseline.

METHODS: Total bilirubin (TB), direct bilirubin (DB) and liver transaminases (AST and ALT) were checked routinely at baseline and at thow, four, eight and 12 weeks after starting treatment. Within the first month of treatment, blood was also taken for NAT2 genotyping. The identification of the three NAT2 polymorphisms that are associated with a slow acetylator status - 481C to T (NAT2*5), 950G to A (NAT2*6) and 857G to A (NAT2*7) was carried out by polymerase chain reaction-restriction fragment length polymorphism. All patients were followed up for a total of six months. The presense of any adverse effects like gastroinstestinal symptoms, rash, hepatitis or drug fever was also monitored.

RESULTS: A total of 24 children [mean age: 5 years; 11 males] were included. Majority (96%) were diagnosed by passive detection and mean Z score was - 1.38 (1 to -3). No patient developed hepatotoxicity or any side effects to anti-TB drugs. In 23 patients who had NAT2 genotyping, 39% and 22% were alleles homozygous for the NAT2*6 and NAT2*7, respectively. There was a combination of alleles in only three (13%) subjects.

CONCLUSION: NAT2*6 and NAT2*7 alleles associated with a slow acetylator status were detected among our patients although the presence of these variants did not lead to any hepatotoxicity nor any treatment-related side effects. A larger study with broader genotype analysis is needed to confirm the present findings.

Human ; Male ; Female ; Adolescent ; Child ; Child Preschool ; Infant ; Isoniazid ; Pyrazinamide ; Rifampin ; Alleles ; Bilirubin ; Liver Function Tests ; Transaminases ; Antitubercular Agents ; Tuberculosis, Pulmonary ; Hepatitis ; Polymorphism, Genetic

Background: Pulmonary TB in children remains to be a burden in the Philippines. Diagnosis remains to be a challenge for pediatricians due to its paucibacillary nature, difficulty in obtaining specimens, cost of test as well as the varied sensitivity of the different tests available. Gastric aspirate (GA), commonly used for bacteriological diagnosis of pulmonary tuberculosis (PTB) in children, involves an invasive procedure that may cause discomfort and sometimes require admission. Nasopharyngeal aspirate (NPA), on the other hand, can be easily and non-invasively obtained but is currently not a recommended specimen for testing for PTB. Objectives: This study aims to determine the accuracy of NPA GeneXpert in diagnosing PTB among pediatric patients 0-18 years old with presumptive TB using GA GeneXpert as the initial screening test and GA TB culture as gold standard. Methodology: This prospective, cross-sectional diagnostic study involved collection of single NPA and GA specimens for GeneXpert and TB culture in 100 patients with presumptive PTB seen at a tertiary government hospital in the Philippines. Results: Of the one hundred pediatric patients (mean age 6 ± 5.63 years) enrolled, 50 were clinically diagnosed PTB, 16 bacteriologically-confirmed and 34 were not PTB disease. Sensitivity, specificity and predictive values with 95% confidence intervals of the NPA GeneXpert were determined compared to GA GeneXpert and GA culture. Sensitivity, specificity, positive and negative predictive values of the NPA GeneXpert compared to GA GeneXpert were 70%, 96.67%, 70% and 96.67%, respectively. While NPA GeneXpert compared to GA TB culture were 40%,91.58%, 20% and 96.67%, respectively. Conclusion GeneXpert testing on a single NPA specimen is a highly specific and rapid test that can be used to diagnose PTB in pediatric patients, particularly where gastric aspiration or mycobacterial culture is not feasible.
Tuberculosis, Pulmonary

Background/Objective: An outbreak of nosocomial infections through nasal carriage of organisms by health care workers may also occur. The health care workers (who are in close contact with the patients are possible sources of hospital-acquired infections. Staphylococci are a leading cause of bacteremia, surgical wound infections and nosocomial infection in many areas around the globe. The objective of this study was to determine the nasal carriage rate of Staphylococcus aureus among health care workers in a pediatric intensive care unit. Methods: Twenty six healthcare workers in a pediatric intensive care unit of a tertiary hospital were included. Cultures from the anterior nares were obtained using a sterile cotton tip swab, which was moistened with sterile normal saline solution. Samples were then analyzed using standard microbiological methods. The susceptibilities of the isolates to antibiotics were then determined by the Kirby Bauer disk diffusion method. Nasal carriage rate of Staphylococcus aureus was determined. Results: The mean age of the subjects was 35 years (range 22-56) old. There were 20 nurses (76.9%), 4 (15.4%) nurse assistants, and 2(7.7%) utility workers; 3 (11. 5%) were males and 23 (88.5%) were females. Two subjects (7.7%) grew Staphylococcus aureus. Both reported 100% sensitivity to all tested antibiotics except for Penicillin G which showed 100% resistance. Twenty four of the subjects (92.3%) grew Staphylococcus epidermidis, 5 (20.83%) were methicillin resistant. All showed 100% sensitivity to Gatifloxacin, Levofloxacin, Oxacillin, and Vancomycin. There was high resistance (62.5%) to Penicillin G. Conclusion The nasal carriage rate (7.7%) of Staphylococcus aureus in this study is lower compared to earlier reports. The results of this study showed higher nasal carriage of Staphylococcus epidermidis (92.3%).
Staphylococcus ; Staphylococcus aureus ; Methicillin-Resistant Staphylococcus aureus

The most common cause of pyogenic infection of the skin and soft tissues in children is Staphylococcus aureus, a fast-emerging problem due to its accompanying significant cost and morbidity. The popularity of herbal medications has increased due to the search for cheaper and more accessible alternatives. However, data is still lacking to back up these claims. Although a few in vitro studies have tested Neem leaf extract on S. aureus, there are none done on Methicillin-resistant Staphylococcus aureus (MRSA) despite the fact that it is being marketed for such purposes. Objectives: This study aims to determine if Neem leaf extract (Azadirachta indica) has antibacterial properties against Methicillin-sensitive and Methicillin-resistant Staphylococcus aureus and to compare the anti-staphylococcal properties of Neem leaf extract with oxacillin, vancomycin, mupirocin, and povidone iodine. Methods: An in vitro experimental study was performed using Neem leaf, properly identified and verified, was subjected to ethanol extraction of its active ingredients then diluted to produce 25%, 50%, 75%, and 100% concentrations. Standard strains of Staphylococcus aureus and clinical isolates of MRSA where inoculated on blood agar plates and subjected to the standardized disc susceptibility testing method. Zones of inhibition were measured for each test extract and compared to currently used medications, namely oxacillin, vancomycin, mupirocin, and povidone iodine with the pure diluent as negative control. The data was analyzed using difference of means hypothesis testing; it utilized the student's t-test to determine significance. Results: A trend of increasing antibacterial activity was noted with increasing concentration of the extract. Zones of inhibition started to appear at 50% concentration for S. aureus and 75% for MRSA. The antibiotics were able to produce greater zones of inhibition than the Neem extracts. Conclusion: Data from this study strongly suggest that the ethanol extract from Neem leaves exhibits in vitro antibacterial activity against both Staphylococcus aureus and MRSA with greatest zones of inhibition noted at 100% concentration.
STAPHYLOCOCCUS AUREUS ; AZADIRACHTA ; ANTI-BACTERIAL AGENTS ; METHICILLIN ;

Objective: This study aimed to determine the clinical profile and outcome of pediatric patients with acute viral encephalitis syndrome admitted at a single tertiary government hospital. Methods: All pediatric patients admitted at the Philippine General Hospital from January 2011 to December 2014 and discharged with a final diagnosis of acute viral encephalitis were included. After demographic data, clinical manifestations, and laboratory findings were collected, the outcome was determined using the Modified Rankin Scale for children. The data were summarized using descriptive statistics. The median test was used to compare the outcomes while the chi-square test was used to analyze the comparison between study groups. Results: Sixty-four patients diagnosed with acute viral encephalitis syndrome were included in the study. The highest number of cases was reported in ages 1- 4 years (32.81%) and among the male population (68.75%). The most common symptoms were seizure (46.87%), abnormal behavior (21.88%), and altered sensorium (20.31%). Forty-four patients had CSF viral studies done, and among them, the 11 (25%) were positive for Japanese encephalitis. The modified Rankin scale showed that 41 (64.08 %) subjects showed good outcomes, while 23 (35.23%) exhibited poor outcomes. There was no significant difference in the modified Rankin scale for Japanese encephalitis compared to the other etiologic agents of acute viral encephalitis (p value= 0.717). Conclusion In patients with acute viral encephalitis, the most common symptoms were seizures, abnormal behavior, and altered sensorium. Majority of the subjects did not show any significant symptoms and disability. No difference was seen in the clinical outcome of patients infected with Japanese encephalitis compared to other etiologic agents, but these results need to be verified by larger studies.<
Acute Febrile Encephalopathy ; Encephalitis, Japanese

Rationale: A paired comparison of reactivity to purified protein derivative 2 TU PPD RT-23 and 5 TU PPD-S in children with clinical manifestations of tuberculosis was done to assess if 2 TU PPD RT-23 can be used instead of 5 TU PPD-S in routine Mantoux testing in the country. Objective: To determine the correlation of skin test reactivity to 2 TU PPD RT-23 and 5 TU PPD-S. Study Design: Cross Sectional Study. Methods: Two simultaneous skin tests using 2 TU PPD RT-23 and 5 TU PPD-S were performed. Each dose was randomly assigned in a blinded manner to the right or left forearm and read after 72 hours. Correlation between the size of induration obtained with 2 TU PPD RT-23 and with 5 TU PPD-S was done, as well as, correlation between tuberculin reactivity and age, gender, nutritional status, presence of BCG vaccination, exposure, and clinical manifestations. A p-value <0.05 was considered statistically significant. Results: Sixty five patients were included in the study. The overall mean difference in paired reaction sizes for the two doses was-1.02 + 2.8 mm (range of -11 to 3 mm). Using the present guidelines in the country to determine a positive tuberculin skin test, 27 (41.5 %) patients were positive when tested with 2 TU PPD RT-23 and 33 (50.8 %) patients were positive when tested with 5 TU PPD. The mean PPD size with 2 TU was 4.7 mm + 6.1 mm compared to 5.8 mm + 6.1 mm with 5 TU. PPD skin test reactivity with the two reagents was highly correlated (intraclass correlation 0.88; 95% CI 0.83-0.94). There was no significant association between age, gender, nutritional status, presence of BCG vaccination, TB exposure, and clinical manifestations to tuberculin reactivity. Conclusion: Tuberculin skin test reactivity among children, who were with clinical manifestations of tuberculosis and tested with 2 TU PPD RT-23 and 5 TU PPD-S, were found to be comparable. Age, gender, nutritional status, presence of BCG vaccination, TB exposure, and clinical manifestations were not factors influencing the size of the PPD reaction. 2 TU PPD RT-23 can be used instead of 5 TU PPD-S in routine Mantoux testing.
Human ; Male ; Female ; Adolescent ; Child ; Child Preschool ; Infant ; Infant Newborn ; TUBERCULIN ; SKIN TESTS ; TUBERCULOSIS

Background: The features and outcome of hepatobiliary tuberculosis (HBTB) have not been extensively reported in children. Objective: To describe the clinical, biochemical, radiologic, microbiologic and histologic features and outcome of children diagnosed with HBTB. Methods: Data of HBTB patients aged 0-18 years were collected by review of medical records and as they were admitted. Cases were classified as bacteriologically-confirmed (positive AFB smear, TB culture or PCR of bile/liver tissue) or clinically-diagnosed (clinical, histologic and/or radiologic evidence). Results: A total of 36 patients were included (mean age: 13yrs; 64% males): three bacteriologically-confirmed and 33 clinically-diagnosed. Most common signs/symptoms were weight loss (69%), fever (67%), hepatomegaly (61%) and jaundice (53%). Of the total, 68% had hypoalbuminemia, 50% increased transaminases and 47% prolonged prothrombin time. Fifteen (42%) patients were AFB positive on various microbiologic specimens. Most common imaging finding was hepatic calcification (64%). Of 11 patients with liver biopsy, seven (64%) had chronic/ granulomatous inflammation. All 36 were managed medically. Eight were lost to follow up, six died, and 22 (61%) are alive, nine with complete resolution of liver disease. Conclusion Hepatobiliary tuberculosis presents with non-specific clinical and biochemical findings. Several investigations are necessary to confirm the diagnosis. Overall response to anti-TB treatment is satisfactory with possible resolution of liver disease.
Polymerase Chain Reaction ; Granuloma

Objective: To describe the clinical, biochemical, microbiologic, radiologic and histological features and outcome of intestinal TB. Methods: Medical records of patients diagnosed with intestinal TB were reviewed. Cases were considered bacteriologically-confirmed if intestinal tissue was positive on smear culture or polymerase chain reaction (PCR); and clinically-diagnosed if with clinical, histologic, and radiologic evidence of extra-pulmonary TB. Results: Fifteen patients [Mean (SD) age: 13 (4) years; 53% females] were included. One was bacteriologically-confirmed; and fourteen were clinically-diagnosed. Fever (87%) and abdominal pain (73%) were commonly seen. Seven (47%) had anemia, 5 (33%) leukocytosis and 10 (71%) hypoalbuminemia. Eleven (73%) were positive on smear or TB PCR of various specimens. Nine of 10 (90%) patients with an abdominal CT scan had thickening of bowel loops. Three with intestinal biopsy demonstrated caseation granuloma. Fourteen patients were given quadruple anti-TB medications. Six had surgery, 8 had no disease-related complications, 4 died of sepsis and 3 were lost to follow up. Conclusion Intestinal TB presents with non-specific clinical and laboratory features. Radiologic findings may provide a clue to the diagnosis. Histologic confirmation in intestinal tissue was only seen in a few cases. The prognosis was favorable for patients who completed the anti-TB treatment.
Tuberculosis, Extrapulmonary ; Mycobacterium tuberculosis

Introduction: Healthcare-associated infections (HCAIs) are a common complication of prolonged hospital stay, leading to increased morbidity and mortality. This study aims to determine the effectiveness of daily chlorhexidine bathing in reducing HCAIs in the pediatric intensive care unit (PICU). Methodology: This is a randomized controlled, observer-blinded study conducted over a 6-month period. Included were 2 months to 18-year-old patients admitted to the PICU, randomly assigned to daily bathing with 2% chlorhexidine or to the standard practice of bathing with plain soap and water. Primary outcome was the incidence of HCAI in each group. Results: A total of 50 patients were enrolled in the study. Overall incidence of HCAI was lower in the chlorhexidine group compared to the control group (12% versus 36%, RR=0.33, 95% CI 0.10 – 1.09, p=0.047). Incidence density rate was lower in the chlorhexidine group (5.91 versus 21.03 infections per 1000 person-days, p=0.049). Ventilator-associated pneumonia and bloodstream infections were lower in the chlorhexidine group, but results were not statistically significant. There were no significant differences in mortality rates and length of hospital stay. One adverse event of transient rash occurred in the chlorhexidine group. Conclusion Daily chlorhexidine bathing may be more effective in reducing HCAIs in the PICU compared to standard care.
Chlorhexidine ; Intensive Care Units, Pediatric