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

[This corrects the article DOI: 10.1371/journal.pone.0258936.].

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Epidemiological and clinical characteristics of children with confirmed COVID-19 infection in a tertiary referral hospital in Manila, Philippines.

BACKGROUND: COVID-19 has challenged the under-resourced health systems of low- and middle-income countries, significantly affecting child health. Available published data on Filipino children with COVID-19 infection are limited. This study aims to describe the epidemiological and clinical characteristics of pediatric patients with confirmed COVID-19 in an infectious disease hospital in Manila, Philippines. MAIN TEXT: This cross-sectional study reviewed data on patients ages 0 to 18 years with confirmed COVID-19 infection, admitted to San Lazaro Hospital from January 25, 2020 to January 25, 2022. Demographic data and clinical characteristics obtained from COVID-19 case investigation forms were summarized and compared between severe and non-severe cases. Risk factors for disease severity and mortality were analyzed. Of 115 patients, 64% were males. There were 87 patients (75.7%) with asymptomatic, mild, or moderate disease, and 28 cases (24.3%) with severe or critical illness. The median age of all patients was 10 years (interquartile range: 4-15 years). The majority of patients (40.9%) were adolescents ages 13 to 18 years. Predominant symptoms were fever (73.9%) and cough (55.7%). Patients with severe or critical illness were more likely to experience difficulty of breathing (55.2% vs 44.8%, p < 0.001), and have a longer hospital stay (11 days vs 8 days, p = 0.043). Among all patients, 48.7% had at least one underlying disease; and common infectious co-morbidities were tuberculosis (17.4%), dengue (12.2%), and HIV (4.3%). Having tuberculosis (p = 0.008) or at least one co-morbidity (p < 0.001) was associated with disease severity. Ten patients (8.7%) died; and mortality was higher among those with severe or critical illness (80% vs 20%, p < 0.001). Sepsis (p = 0.020) or having at least one co-morbidity (p = 0.007) was associated with death. CONCLUSION: Children of all ages remain susceptible to COVID-19 infection, and usually present with mild or moderate symptoms. In this study, many adolescents are affected, highlighting the value of COVID-19 vaccination in this age group. Understanding the clinical features of COVID-19 in Filipino children is essential to identifying and optimally managing those at highest risk of severe disease.

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.

Measles outbreak in the Philippines: epidemiological and clinical characteristics of hospitalized children, 2016-2019.

BACKGROUND: Measles outbreaks increased worldwide during 2017-19. The largest outbreak in the World Health Organisation Western Pacific region occurred in the Philippines where first-dose measles-containing vaccine (MCV1) coverage had reduced to 75% in 2018. The aim of this study was to summarise paediatric measles admissions to the national infectious diseases referral hospital in Manila during 2016 to 2019. METHODS: A retrospective single-centre observational study including 5,562 children aged under five years admitted with measles from January 2016 to December 2019. We summarised sociodemographic and clinical characteristics, vaccine status, reported exposures, and outcomes. Univariable and multivariable logistic regression analyses were undertaken to assess associations between different characteristics of hospitalised children and death. FINDINGS: The median age of children hospitalised with measles was 11 months (interquartile range: 7-28). 84·5% of cases were reported not to have received any MCV. The risk of mortality was 3·2%, with 41% of deaths occurring among children aged less than 9 months. No children died who had received two MCV. The following characteristics were significantly associated with mortality in the multivariable analysis: age group, residence outside of the national capital region, not having received any MCV, duration between onset of fever and hospital admission of 7-14 days compared with 0-3 days, not receiving vitamin A supplementation, having pneumonia, and gastroenteritis. INTERPRETATION: The Philippines remains at risk of future measles epidemics. Routine immunization needs to be strengthened and earlier timing of MCV1 requires further evaluation to reduce measles incidence and mortality.

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.

Epidemiological and clinical characteristics of the first 500 confirmed COVID-19 inpatients in a tertiary infectious disease referral hospital in Manila, Philippines.

BACKGROUND: The Philippines has been one of the most affected COVID-19 countries in the Western Pacific region, but there are limited data on COVID-19-related mortality and associated factors from this setting. We aimed to describe the epidemiological and clinical characteristics and associations with mortality among COVID-19-confirmed individuals admitted to an infectious diseases referral hospital in Metro Manila. MAIN TEXT: This was a single-centre retrospective analysis including the first 500 laboratory-confirmed COVID-19 individuals admitted to San Lazaro Hospital, Metro Manila, Philippines, from January to October 2020. We extracted clinical data and examined epidemiological and clinical characteristics and factors associated with in-hospital mortality. Of the 500 individuals, 133 (26.6%) were healthcare workers (HCW) and 367 (73.4%) were non-HCW, with HCW more likely presenting with milder symptoms. Non-HCW admissions were more likely to have at least one underlying disease (51.6% vs. 40.0%; p = 0.002), with hypertension (35.4%), diabetes (17.4%), and tuberculosis (8.2%) being the most common. Sixty-one (12.2%) died, comprising 1 HCW and 60 non-HCW (0.7% vs. 16.3%; p < 0.001). Among the non-HCW, no death occurred for the 0-10 years age group, but deaths were recorded across all other age groups. Compared to those who recovered, individuals who died were more likely to be older (p < 0.001), male (p = 0.015), report difficulty of breathing (p < 0.001), be HIV positive (p = 0.008), be intubated (p < 0.001), categorised as severe or critical (p < 0.001), have a shorter mean hospital stay (p < 0.001), or have an additional diagnosis of pneumonia (p < 0.001) or ARDS (p < 0.001). CONCLUSION: Our analysis reflected significant differences in characteristics, symptomatology, and outcomes between healthcare and non-healthcare workers. Despite the unique mix of cohorts, our results support the country's national guideline on COVID-19 vaccination which prioritises healthcare workers, the elderly, and people with comorbidities and immunodeficiency states.

If Not COVID-19 What Is It? Analysis of COVID-19 versus Common Respiratory Viruses among Symptomatic Health Care Workers in a Tertiary Infectious Disease Referral Hospital in Manila, Philippines.

The COVID-19 global pandemic is entering its second year. In this short report we present additional results as a supplement to our previous paper on COVID-19 and common respiratory virus screening for healthcare workers (HCWs) in a tertiary infectious disease referral hospital in Manila, Philippines. We sought to understand what etiologic agents could explain the upper/lower respiratory tract infection-like (URTI/LRTI-like) symptoms exhibited by 88% of the 324 HCWs tested. Among the patients who had URTI/LRTI-like symptoms, only seven (2%) were positive for COVID-19, while 38 (13%) of the symptomatic participants were identified positive for another viral etiologic agent. Rhinovirus was the most common infection, with 21 (9%) of the symptomatic participants positive for rhinovirus. Based on these results, testing symptomatic HCWs for common respiratory illnesses in addition to COVID-19 should be considered during this time of global pandemic.

Correction to: Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines.

[This corrects the article DOI: 10.1186/s41182-020-00241-8.].

COVID-19 Screening for Healthcare Workers in a Tertiary Infectious Diseases Referral Hospital in Manila, the Philippines.

COVID-19 is an emerging disease threatening the lives of patients and healthcare workers (HCWs) alike. In this article, we present initial results of COVID-19 screening performed among the hospital staff of an infectious diseases referral hospital in Manila, the Philippines. Of 324 HCWs tested, eight were positive; only one was exposed to COVID-19 patients, whereas seven others belonged to two different departments. Routine screening of hospital staff is invaluable for the safety of the HCWs and the patients in hospitals and should be performed on a regular basis. In monitoring HCWs, we protect one of our most valuable assets against COVID-19.

Correction to: First COVID-19 infections in the Philippines: a case report.

[This corrects the article DOI: 10.1186/s41182-020-00203-0.].

First COVID-19 infections in the Philippines: a case report.

BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient's condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.

Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to almost every region and country in the world, leading to widespread travel restrictions and national lockdowns. Currently, there are limited epidemiological and clinical data on COVID-19 patients from low and middle-income countries. We conducted a retrospective single-center study of the first 100 individuals with suspected COVID-19 (between Jan. 25 and Mar. 29, 2020) admitted to San Lazaro Hospital (SLH), the national infectious diseases referral hospital in Manila, Philippines. RESULTS: Demographic data, travel history, clinical features, and outcomes were summarized and compared between COVID-19 confirmed and non-confirmed cases. The first two confirmed cases were Chinese nationals, admitted on Jan. 25. The third confirmed case was a Filipino, admitted on Mar. 8. Trends toward confirmed COVID-19 cases not reporting international travel and being admitted to SLH from the densely populated area of Manila city were observed during Mar. 8-29. All 42 of the 100 confirmed COVID-19 cases were adults, 40% were aged 60 years and above and 55% were male. Three were health workers. Among individuals with suspected COVID-19, confirmed cases were more likely to be older, Filipino, not report international travel history and have at least one underlying disease, particularly diabetes, report difficulty in breathing, and a longer duration of symptoms. In over 90% of non-COVID-19 cases, the alternative diagnosis was respiratory. Nine (21%) confirmed cases died. The median duration from symptoms onset to death was 11.5 (range: 8-18) days. CONCLUSIONS: Imported COVID-19 cases have reduced but local transmission persists and there is a trend toward cases being admitted to SLH from densely populated areas. This study highlights the difficulty in diagnosing COVID-19 on clinical grounds and the importance of diagnostic capacity in all settings. Difficulty of breathing was the only symptom associated with COVID-19 infection and should alert clinicians to the possibility of COVID-19. Clinical characteristics of confirmed COVID-19 cases and a hospital case fatality rate of 21% are comparable with other settings.