BACKGROUND

Pneumococcal vaccination has been widely used for the prevention of pneumococcal disease, with two types of vaccines available since 2009. With the World Health Organization (WHO) recommendation of incorporating pneumococcal conjugate vaccines (PCVs) in National Immunization Programs (NIPs) worldwide, a ten-valent PCV (PHiD-CV) was initially introduced in the Philippines in 2012. This, however, transitioned to the use of the 13-valent PCV (Prevnar) subsequent to the recommendation of the Formulary Executive Council in 2014.

This review aimed to present evidence on pneumococcal disease and vaccine inclusion in the Philippine NIP from 2005 - 2021.

This narrative review compiled articles on Pneumococcus from January 2005 to October 2021, sourcing literature from databases such as BIOSIS Preview, CAB Direct, Embase, Google Scholar, and others.

In the Philippines, there was a shift in prevalent serotypes of Streptococcus pneumoniae among children under five following the introduction of PCV13 in the National Immunization Program in 2014, with serotype 14 becoming the most common by 2018, and a significant reduction in isolates reported in 2020, where only serotypes 5, 19A, and 23F were identified among invasive strains. The immunogenicity results of a potential vaccine candidate should be factored into the overall evidence when conducting a reassessment of PCV.

As part of the decision making about the inclusion of the PCVs in the NIP of the Philippines, various factors such as local epidemiology, vaccine supply, cost, and programmatic characteristics must be careful weighed. Enhancing laboratory and surveillance capacity are essential to provide evidencebased decision-making in terms of existing serotype distribution and antimicrobial resistance (AMR) profile in the country. With the introduction of a new affordable formulation of a 10-valent PCV offering a comparable serotype coverage, the reassessment of choice of PCV with the consideration of all three formulations, namely PCV13, PHiD-CV, and SIIPL-PCV, may be warranted.

BACKGROUND

The World Health Organization (WHO) estimates that in 2015, approximately 325 million or 4.4% of the global population were living with chronic hepatitis B or hepatitis C infection. In the same year, around 1.34 million died from this disease.

This study aimed to estimate the burden of hepatitis B in the Philippines and to determine the costeffectiveness of possible interventions.

This study utilized the Center for Disease Analysis Foundation’s (CDAF’s) mathematical disease burden model of hepatitis B. Model inputs were collected using literature review, key informant interviews, expert panel interviews, and records review, and were validated through a series of round table discussions with experts.

Results show that in 2017, the prevalence of chronic hepatitis B infection in the Philippines was 9.7%, equivalent to 10 million infected individuals. Although the model projects a decreasing trend in chronic hepatitis B virus (HBV) infections, liver-related mortality and morbidity due to these viruses are expected to rise if the status quo is maintained. Results show that substantial increase in government subsidy for WHO elimination scenarios would be required to achieve cost-effective outcomes.

Hepatitis B remains a huge problem in the Philippines. The HBV modelling exercise reveal that it will be worthwhile and cost-effective to adhere to the WHO elimination targets. A substantial financial investment will be necessary to do so, specifically a significant scale up in the screening, diagnosis, treatment, and monitoring of patients with HBV. While this modelling exercise does not yield burden of disease as accurate as a prevalence survey, experts consulted in the round table discussions agreed with the modelling inputs.

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.
COVID-19 ; COVID-19 Serotherapy

Background: The COVID-19 pandemic became a severe public health threat to the Philippines, overwhelming the health system and its healthcare workers. As infections spread globally, it became imperative to understand the infection prevention practices (e.g., face mask-wearing, handwashing, social distancing) to better understand the pandemic and its effects on the healthcare workforce. Objective: The study aims to describe the sociodemographic and medical profile and the COVID-19 infection prevention practices, and the correlation between both among employees of a medical center in the National Capital Region (NCR), Philippines, Methods: The analytic cross-sectional study utilized an online survey administered to employees of a medical center in NCR, Philippines. A total of 112 responses were analyzed. Descriptive statistics were used to analyze respondents’ sociodemographic and medical characteristics and summarize their COVID-19 infection prevention practices. Spearman’s rank correlation and Pearson’s chi-square tests were performed to determine the association of the respondents’ sociodemographic and medical profiles with their corresponding infection prevention practices. Results: Majority of respondents were between ages 30-50 (52.68%), female (71.43%), with college (83.93%) as their highest educational attainment, single (70.54%), and without comorbidities (66.07%). 76.5% (72/94) of respondents living in multi-person households lived with familial ties, and 59.6% (56/94) of respondents living in a multi-person household lived with at least one member considered a high-risk individual (i.e., a senior citizen with comorbidities). The respondents practiced face mask-wearing (4.92) and respiratory etiquette (4.90) the most, whereas reduction of unnecessary outings (3.81), not drinking alcohol (3.81), and sleeping at least 7 hours per day (3.42) were least practiced. Results showed that only age and having chronic kidney disease correlated with infection prevention practices with a p-value of <0.05, showing that people with chronic kidney disease and those aged 30-50 were more likely to engage in infection prevention practices. Conclusion The study findings provide insight into sociodemographic and medical factors that may contribute to adherence to infection prevention practices among the hospital-based workforce. Recommendations for further research were discussed.
COVID-19 ; Hospitals

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.
Female ; Humans ; Epithelial Cells/pathology* ; Hyperplasia/pathology* ; Papilloma/pathology* ; Adult ; Middle Aged ; Mammary Glands, Human/pathology* ; Breast Neoplasms/pathology* ; Carcinoma, Lobular/complications* ; Carcinoma, Ductal/complications*

Humans ; B7-H1 Antigen ; Neoplasms/genetics*

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.
Male ; Female ; Humans ; Child ; Glomus Tumor/surgery* ; Endothelial Cells/pathology* ; Paraganglioma, Extra-Adrenal/pathology* ; Immunohistochemistry

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl₂ and hypoxia (1%O₂) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl₂ and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; HeLa Cells ; Von Hippel-Lindau Tumor Suppressor Protein/genetics* ; Mutation ; Signal Transduction ; Luciferases/therapeutic use* ; Hypoxia/genetics* ; RNA, Messenger ; Lipids/therapeutic use* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Background and Objectives: Tuberculosis (TB) remains a public health problem in the Philippines despite trends indicating a decline in the burden of disease. Persons who use drugs who are confined in government-retained drug abuse treatment and rehabilitation centers (DATRCs) face an increased risk for TB because of the congestion in the facility coupled with the absence of guidelines on TB management specific to DATRCs. Thus, this study was conducted to document the current case finding and case holding practices as well as TB treatment pathway in six (6) Luzon-based, government-retained DATRCs.

Methods: Key informant interviews were conducted with DATRC personnel involved in TB diagnosis and management in six selected DATRCs in Luzon, Philippines. Interviews were transcribed and coded for thematic analysis. We compared the DATRC practices with the provisions of the 2014 National TB Control Program (NTP) Manual of Procedures. Results were validated through a workshop with (a) a group of physicians and rehabilitation practitioners assigned in other DATRCs; and (b) a group of experts who have experience in managing or overseeing DATRCs in the country.

Results: Two physicians and four nurses participated in the interviews. Variations in case finding and case holding practices in six DATRCs have been found. National guidelines exist for congregate settings but are more specific to jails/prisons, which are administratively and operationally different from DATRCs.

Conclusion: Development of special guidelines for TB case finding and case holding in DATRCs as well as staff training on the latest NTP Manual of Procedures are recommended. However, gaps and inequities posed by the current set-up underscore the need to address health system-wide factors affecting the practice and performance of these facilities.

Key Words: tuberculosis, case finding, case holding, drug abuse treatment and rehabilitation centers, Philippines

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.