Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study.

OBJECTIVE: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. METHODS: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. RESULTS: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. CONCLUSIONS: The study vaccine  had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs.

Design and Evaluation of Risk Assessment Tools to Identify Pediatric Tuberculosis Infection in Bohol, the Philippines, a Low-HIV- and High-TB-Burden Setting.

Identifying children with, or at substantial risk of, Mycobacterium tuberculosis infection (TBI) and providing TB preventive therapy (TPT) represent an important, yet challenging, strategy in curbing the global burden of childhood TB. Risk assessment scoring tools, which quantify risks associated with unique factors characterizing an individual, could act as a surrogate measure of TBI risk and guide effective and efficient TPT delivery. We assessed important risk factors of childhood TBI and created risk assessment tools through secondary analysis of data from a large, community-based childhood TB prevalence study in the island province of Bohol in the Philippines, a low-HIV- and high-TB-burden, post-disaster setting. We identified four factors that were statistically associated with acquiring TBI-being 5 years or older, having a known TB contact, having a known TB contact who was either the mother or another primary caregiver, and living in a high-TB-burden municipality. We created 2-item, 4-item, and 9-item scores intended to identify child TBI in this low-resource, low-HIV-, and high-TB-burden setting. In addition to the design, evaluation, and impact analysis of these generalizable and valuable risk assessment tools, our study findings emphasize the necessity of targeting both household and community-associated transmissions of childhood TBI to achieve the global goal to end TB.

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.

Prevalence of Tuberculosis in Children After Natural Disasters, Bohol, Philippines.

In 2013, a severe earthquake and typhoon affected Bohol, Philippines. To assess the postdisaster risk for emergence of Mycobacterium tuberculosis infection in children, we conducted a cross-sectional multistage cluster study to estimate the prevalence of tuberculin skin test (TST) positivity and tuberculosis (TB) in children from 200 villages in heavily affected and less affected disaster areas. Of the 5,476 children we enrolled, 355 were TST-positive (weighted prevalence 6.4%); 16 children had active TB. Fourteen (7%) villages had >20% TST-positive prevalence. Although prevalence did not differ significantly between heavily affected and less affected areas, living in a shelter with >25 persons approached significance. TST positivity was independently associated with older age, prior TB treatment, known contact with a person with TB, and living on a geographically isolated island. We found a high TST-positive prevalence, suggesting that national programs should consider the differential vulnerability of children and the role of geographically isolated communities in TB emergence.

Influenza in the Asia-Pacific region: Findings and recommendations from the Global Influenza Initiative.

The fourth roundtable meeting of the Global Influenza Initiative (GII) was held in Hong Kong, China, in July 2015. An objective of this meeting was to gain a broader understanding of the epidemiology, surveillance, vaccination policies and programs, and obstacles to vaccination of influenza in the Asia-Pacific region through presentations of data from Australia, Hong Kong, India, Indonesia, Malaysia, New Zealand, the Philippines, Taiwan, Thailand, and Vietnam. As well as a need for improved levels of surveillance in some areas, a range of factors were identified that act as barriers to vaccination in some countries, including differences in climate and geography, logistical challenges, funding, lack of vaccine awareness and education, safety concerns, perceived lack of vaccine effectiveness, and lack of inclusion in national guidelines. From the presentations at the meeting, the GII discussed a number of recommendations for easing the burden of influenza and overcoming the current challenges in the Asia-Pacific region. These recommendations encompass the need to improve surveillance and availability of epidemiological data; the development and publication of national guidelines, where not currently available and/or that are in line with those proposed by the World Health Organization; the requirement for optimal timing of vaccination programs according to local or country-specific epidemiology; and calls for advocacy and government support of vaccination programs in order to improve availability and uptake and coverage. In conclusion, in addition to the varied epidemiology of seasonal influenza across this diverse region, there are a number of logistical and resourcing issues that present a challenge to the development of optimally effective vaccination strategies and that need to be overcome to improve access to and uptake of seasonal influenza vaccines. The GII has developed a number of recommendations to address these challenges and improve the control of influenza.

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.

Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen content Haemophilus influenzae type b vaccine in Filipino children.

OBJECTIVES: To evaluate the immunogenicity, reactogenicity and safety of primary and booster vaccination with DTPw-HBVLT/Hib2.5 vaccine containing low thiomersal and reduced quantities of Hib polysaccharide (PRP). BACKGROUND: Combined DTP vaccines have high global coverage. Thus, the addition of new antigens to existing DTP vaccines is the most effective way to ensure high coverage. METHODS: 192 healthy infants were randomized to receive the investigational DTPw-HBVLT/Hib2.5 vaccine or licensed DTPw-HBV/Hib10 at 6, 10, 14 weeks. Immune memory to the Hib antigen was assessed through administration of plain PRP challenge at 10 months in 50% of subjects. Challenged and unchallenged subjects respectively received a DTP-HBV or DTPa-HBV/Hib booster at 15-18 months of age. Antibody responses were measured using enzyme-linked immunosorbent assay (ELISA) and reactogenicity was assessed using diary cards. RESULTS: One month post-primary vaccination, 100% and ≥ 93.7% of subjects in both groups had anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL, respectively. Robust responses to PRP were observed after the 10 month plain PRP challenge and booster responses were observed in unchallenged subjects after the booster dose at 15-18 months of age. Post-primary and post-booster responses to the other vaccine antigens were at least as high in the DTPw-HBVLT/Hib2.5 group versus the DTPw-HBV/Hib10 group. The reactogenicity profile of the DTPw-HBVLT/Hib2.5 vaccine was acceptable. CONCLUSION: The DTPw-HBVLT/Hib2.5 combination vaccine with reduced thiomersal and Hib content had equivalent immunogenicity and tolerability versus the full standard DTPw-HBV/Hib10 vaccine. DTPw-HBVLT/Hib2.5 or DTPw-HBV/Hib10 vaccines can contribute to reducing childhood diseases through ensuring high vaccine coverage in mass vaccination programs. ClinicalTrials.gov identifiers: NCT 01061541, NCT00158808.

Profile of pediatric patients with dengue fever/dengue hemorrhagic fever over a five-year period (2000-2004)

Objectives: This study was conducted to determine the clinico-demographic profile of pediatric patients who were admitted for dengue infection at the Research Institute for Tropical Medicine (RITM) from 2000 to 2004. Methods: This is a retrospective, descriptive study. Charts of patients who were less than 19 years of age and were admitted at the RITM due to confirmed dengue (using paired dengue HI titer results) were reviewed. Conclusion: The clinico-demographic profile of patients involved in the study was very similar to that of other studies done, both locally and abroad. By using Spearman's correlation of ranks, the study showed that there was no significant relationship between the severity of dengue infection based on the World Health Organization (WHO) Grade and whether it was a primary or secondary infection with r=.018, p-value=.025.

Priorities and challenges for hepatitis B control in the Philippines and the importance of a vaccine dose at birth.

The Philippines annual birth cohort of over 2 million is the second largest in the Western Pacific Region; 44% of births occur outside health facilities. With third dose infant hepatitis B (HB) vaccine coverage of 43% in 2006, erratic vaccine supply, and lack of policies or processes for universal HB vaccine birth dose delivery, a substantial burden of preventable chronic HB infection continues to occur. Funding, policy, technical and immunization delivery developments now make substantial progress in HB control in the Philippines possible. These developments can help expand access to trained birth care and essential postnatal care for mothers and their newborn.

Primary vaccination with a new heptavalent DTPw-HBV/Hib-Neisseria meningitidis serogroups A and C combined vaccine is well tolerated.

OBJECTIVE: Safety and reactogenicity of a new heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine was compared with a widely used pentavalent DTPw-HBV/Hib vaccine. METHODS: Three phase III randomized studies comparable in design and methodology, in which healthy infants received DTPw-HBV/Hib-MenAC (N=1334) or DTPw-HBV/Hib (N=446) at 2, 4, and 6 months, were pooled for analysis. Solicited symptoms were recorded for 4 days, and unsolicited adverse events for 31 days after each dose. Serious adverse events (SAEs) were recorded throughout the studies. RESULTS: There were no significant differences between the two groups in the proportion of subjects with fever >39.5 degrees C or >40.0 degrees C (p<0.005). Compared to group DTPw-HBV/Hib, a significantly higher percentage of subjects in group DTPw-HBV/Hib-MenAC reported fever >39 degrees C (21.2% vs. 14.8%, p=0.004). Fever subsided quickly, did not lead to differences in attendance to medical services and did not increase from dose to dose. Sixty-seven SAEs were reported, 56/1334 (4.2%) in group DTPw-HBV/Hib-MenAC and 11/446 (2.5%) in the DTPw-HBV/Hib group. CONCLUSION: Overall, the heptavalent and pentavalent vaccines had similar safety profiles. The difference observed in percentage of subjects with fever >39 degrees C did not lead to differences in medically attended visits for fever.