Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

BACKGROUND: Cell-culture-derived influenza vaccines may enable a closer antigenic match to circulating strains of influenza virus by avoiding egg-adapted mutations. METHODS: We evaluated the efficacy of a cell-culture-derived quadrivalent inactivated influenza vaccine (IIV4c) using a Madin-Darby canine kidney cell line in children and adolescents 2 to less than 18 years of age. During three influenza seasons, participants from eight countries were enrolled in an observer-blinded, randomized clinical trial comparing IIV4c with a noninfluenza vaccine (meningococcal ACWY). All the participants received a dose of a trial vaccine. Children 2 to less than 9 years of age without previous influenza vaccination who were assigned to the IIV4c group received a second dose on day 29; their counterparts who were assigned to the comparator group received placebo. Participants were followed for at least 180 days for efficacy and safety. The presence of influenza virus in nasopharyngeal swabs from participants with influenza-like illness was confirmed by reverse-transcriptase-polymerase-chain-reaction assay and viral culture. A Cox proportional-hazards model was used to evaluate the efficacy of IIV4c as measured by the first occurrence of laboratory-confirmed type A or B influenza (primary end point). RESULTS: Between 2017 and 2019, a total of 4514 participants were randomly assigned to receive IIV4c or the meningococcal ACWY vaccine. Laboratory-confirmed influenza occurred in 175 of 2257 participants (7.8%) in the IIV4c group and in 364 of 2252 participants (16.2%) in the comparator group, and the efficacy of IIV4c was 54.6% (95% confidence interval [CI], 45.7 to 62.1). Efficacy was 80.7% (95% CI, 69.2 to 87.9) against influenza A/H1N1, 42.1% (95% CI, 20.3 to 57.9) against influenza A/H3N2, and 47.6% (95% CI, 31.4 to 60.0) against influenza B. IIV4c showed consistent vaccine efficacy in subgroups according to age, sex, race, and previous influenza vaccination. The incidences of adverse events were similar in the IIV4c group and the comparator group. CONCLUSIONS: IIV4c provided protection against influenza in healthy children and adolescents across seasons, regardless of previous influenza vaccination. (Funded by Seqirus; EudraCT number, 2016-002883-15; ClinicalTrials.gov number, NCT03165617.).

Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, compared to standard IPV: A phase 3 observer-blinded, randomised, controlled trial in infants vaccinated at 6, 10, 14 weeks and 9 months of age.

BACKGROUND: A dose-sparing inactivated polio vaccine (IPV-Al), obtained by adsorption of inactivated virus to an aluminium hydroxide adjuvant, can help mitigate global supply and the cost constraints of IPV. The objective of this trial was to demonstrate the non-inferiority of IPV-Al to standard IPV. METHODS: This phase 3, observer-blinded, randomised, controlled trial was conducted at 5 investigational sites in the Philippines. Infants not previously vaccinated with any polio vaccines were randomised to receive three IPV-Al (n = 502) or IPV vaccinations (n = 500) at 6, 10 and 14 weeks of age plus a booster vaccination at 9 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. RESULTS: Seroconversion rates following primary vaccination with IPV-Al (483 infants in the per-protocol analysis set) or IPV (478 infants) were: polio type 1, 97.1% versus 99.0%; type 2, 94.2% versus 99.0%; and type 3, 98.3% versus 99.6%. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the predefined -10%-point limit: type 1, -1.85% (-3.85; -0.05); type 2, -4.75% (-7.28; -2.52); type 3, -1.24 (-2.84; 0.13). The booster effect (geometric mean titre (GMT) post-booster / GMT pre-booster) was: type 1, 63 versus 43; type 2, 54 versus 47; type 3, 112 versus 80. IPV-Al was well tolerated with a safety profile comparable to that of IPV. Serious adverse events were recorded for 29 infants (5.8%, 37 events) in the IPV-Al group compared to 28 (5.6%, 48 events) in the IPV group. CONCLUSION: Non-inferiority of IPV-Al to IPV with respect to seroconversion was confirmed and a robust booster response was demonstrated. Both vaccines had a similar safety profile. ClinicalTrials.gov identifier: NCT03032419.

Etiology, incidence and outcomes of acute hepatic failure in 0-18 year old Filipino children.

Data on the epidemiology of acute hepatic failure (AHF) among pediatric Filipinos is limited. This study investigated the etiology, outcomes and incidence of AHF among 0-18 year old Filipino children. A hospital-based retrospective and prospective surveillance study was conducted at Philippine General Hospital between January 2000 and December 2006. AHF was defined as onset of coagulopathy and/or encephalopathy < or = 28 days after the onset of symptoms, a patient/ laboratory prothrombin time >2, an elevated bilirubin level and evidence of liver failure complicated by encephalopathy. Blood samples were tested for viral hepatitis antibodies using ELISA (Abbott Lab). AHF incidence rates were calculated with 95% confidence intervals (CI). Twenty-seven subjects were recruited and 26 included in the analysis. The mean age of AHF subjects at the time of hospital admission was 6.9 years (SD:6.09 years). The most frequent etiological agents for AHF were hepatitis A virus (HAV) (19.2%; 5/26) and hepatitis B virus (3.8%; 1/26). Incidence of AHF was 11.05 per 100,000 subject years (95% CI 6.81-15.30). Jaundice was observed in 84.6% (22/26) of subjects and encephalopathy on admission (any grade) was reported in 72.0% of subjects: AHF was fatal in 84.6% (22/26) of subjects. HAV was the most common etiological agent for AHF. Indeterminate causes for AHF indicate the need for further investigation.

Varicella in immunocompromised children at the Philippine General Hospital: A six-year review

Objective: This research aims to describe the profile, clinical course, treatment and outcome of varicella in immunocompromised children at the Philippine General Hospital from January 1999 to December 2004.Study Population: All immunocompromised patients less than 19 years of age with a clinical diagnosis of varicella admitted at the Philippine General Hospital during the study period were included. Method: A review of medical records and monthly census reports of the Pediatric Infectious Disease and Hematology-Oncology Services was conducted. Results: Out of 26 immunocompromised patients who developed varicella during the study period, only 22 charts were available for review. Of these patients, 13 were male and 9 were female. The highest incidence occurred from 0 to 5 years old (41%). Twenty patients had an underlying malignancy in the form of leukemia (14%) and solid organ tumors (6%). Two patients were on chronic steroid therapy (Prednisone) for more than a month due to Nephrotic Syndrome and Myelodysplastic Syndrome with Stevens-Johnson Syndrome. The most common presenting symptom was a rash (68%), with an associated fever seen in 54% of the cases. Majority were treated with acyclovir for an average of 7 days with good response. Nine patients developed complications: mainly, pneumonia and sepsis. Recovery rate was 82%; however, fatality rate was 13.6%. Conclusion: Varicella in immunocompromised children is associated with increased morbidity and mortality. Our patients responded well to sequential intravenous and oral acyclovir. Vaccination of targeted populations such as close household contacts of immunocompromised patients, as well as, healthcare workers may be a good strategy to protect high-risk children from developing the disease and its complications.

Rotavirus acute gastroenteritis among Filipino children

This is a prospective study aimed to determine the clinical profile of pediatric patients less than 5 years old with rotavirus diarrhea seen at the Philippine General Hospital from August 1-September 15, 2001. Ninety-one patients with acute diarrhea were included in the study. Of these 39 patients (42.9 percent) had rotavirus antigen in the stool as detected by the ELISA method. The mean age of the patients was 11.5 months with 61.5 percent of the patients belonging to the 7-12 months of age, mostly well-nourished. The stools were described as watery (74.4 percent), yellow in color (84.7 percent), with no pus, red blood cells or parasite. Average duration of diarrhea prior to consultation was 2.5 +/- 1.8 days with 7 episodes per day. Vomiting, fever and concomitant upper respiratory tract infection were noted in 76.9 percent, 64 percent and 23.7 percent of the patients respectively. A comparison of the rotavirus versus bacterial etiology of diarrhea showed fever and vomiting to be more predominant in rotavirus while dehydration was noted in bacterial isolates. Antibiotic was noted to be given to 38.5 percent rotavirus cases. Increased awareness of rotavirus diarrhea, regarding its high incidence and clinical profile, will help guide physicians in their rational use of antibiotics for patients with acute diarrhea

The effect on various treatment methods on the disinfection of artificially contaminated water

Since waterborne diseases are still an important cause of morbidity and mortality in the Philippine setting, it is evident that the quality of water supplies cannot always be assured, and remedial measures are required to provide consumers with safe drinking water. Boiling is a proven household disinfection method, but doubt regarding its efficacy has led to a search for alternatives. This study was thus performed to compare the efficacy of various methods of water treatment, and to perform a cost analysis for each method Sterile water was seeded with E. Coli ATCC 25922 to a concentration of 10 exponent 5 cfu/ml. Equal amounts were then disinfected by:(1) boiling for 10 minutes; (2) passage through an ultraviolet (UV) light water treatment device (UV Waterworks TM); (3) reverse osmosis (RO). Three replicates were done for each procedure, and for each replicate five aliquots were obtained for (1) immediate testing: (2) testing after 24 hours in room temperature; (3) testing after 24 hours at a temperature of 2-8 degrees C; (4) testing after 48 hours in room temperature; and (5) testing after 48 hours at a temperature of 2-8 degrees C, Samples were analyzed using the spread-plate method on MacConkeys agar. For all samples taken, no growth was seen after 24 hours of incubation Taking into account the cost of consumables for each method, UV disinfection has the advantage of being 200 times less expensive than boiling, which in turn is less costly by 50 percent compared to RO. The increased cost of RO is due to large amount of water discarded during processing. An advantage offered by methods such as RO and UV disinfection is its time-saving aspect. However, households without access to UV or RO units should consider boiling a cost-effective option, so long as manpower and fuel resources are available. (Author)