Unique characteristics of new complete blood count parameters, the Immature Platelet Fraction and the Immature Platelet Fraction Count, in dengue patients

The advanced platelet parameters Immature Platelet Fraction and Immature Platelet Fraction Count have been implemented in clinical practice as measures of thrombopoietic activity, mainly in hematologic disorders that cause thrombocytopenia. The purpose of this observational study was to examine thrombopoiesis as reflected by these 2 new CBC parameters in patients infected with dengue. The study was conducted in infectious disease referral hospital in Metro Manila, the Philippines. We enrolled hospitalized patients at admission who were diagnosed with acute dengue or community acquired bacterial infection (CABI). Immature Platelet Fraction (IPF) and Immature Platelet Fraction Count were evaluated at admission and during hospitalization. A total of 606 patients were enrolled from May 1, 2017 to June 1, 2018. The participants consisted of 152 patients with dengue infection, 180 confirmed CABI, and 274 suspected CABI patients. At admission, the percent IPF (IPF%) of the patients with dengue was significantly higher than that of the confirmed CABI patients (median 3.7% versus 1.9%; p <0.001). In a time course evaluation, there was no significant difference of IPF% between the patients with dengue infection and the confirmed CABI patients in the febrile phase (median 1.9% versus 2.4%; p = 0.488), however, the IPF% of the patients with dengue infection increased to be significantly higher than that of the confirmed CABI patients in the critical phase (median 5.2% versus 2.2%; p <0.001). Our study elucidated the unique characteristics and time-course trends of IPF percent and number (IPF#) in the patients with dengue infection. IPF% and IPF# are potentially valuable parameters in dengue and further investigation is required for the optimal use in clinical practice

A call to protect non-clinical frontliners in the fight against COVID-19: evidence from a seroprevalence study in the Philippines.

Since the COVID-19 pandemic started in 2020, healthcare workers (HCW) and other hospital personnel have been regarded as “frontliners”, and at increased risk of SARS-CoV-2 infection compared to the general population. As such, testing only symptomatic individuals or regular testing of HCWs who directly attend to COVID-19 patients or specimens may underestimate the extent of infection, and actual SARS-CoV-2 seroprevalence. Because of this, the World Health Organization has called for seroepidemiological surveys to assess the extent of infection amongst HCW and other populations to provide timely estimates of COVID-19 virus infection severity and inform public health responses and evidence-based policy decisions

Diphtheria in Metro Manila, the Philippines 2006–2017: A Clinical, Molecular, and Spatial Characterization

BACKGROUND: Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. METHODS: We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). RESULTS: We studied 267 patients (range:12-54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8-50.0%). A higher number of cases and CFR was observed among children <10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types. CONCLUSIONS: Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis

Background: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. Methods: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity.Results: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third—46.0%, fourth—44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9–9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection.Conclusions: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis.

BACKGROUND: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program. METHODS: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity. RESULTS: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third-46.0%, fourth-44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9-9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection. CONCLUSIONS: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines

engue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015?2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa sub-group and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission

An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines

engue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015–2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa sub-group and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission