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.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report.

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Clinical, epidemiological, and spatial features of human rabies cases in Metro Manila, the Philippines from 2006 to 2015.

Rabies remains a public health problem in the Philippines despite the widespread provision of rabies vaccines and rabies immunoglobulin (RIG) as post-exposure prophylaxis (PEP). Detailed descriptions of recent human rabies cases in the Philippines are scarce. This study aimed to describe the clinical, epidemiological, and spatial features of human rabies cases between January 1, 2006, and December 31, 2015. We conducted a retrospective hospital-based case record review of all patients admitted to one referral hospital in Manila who received a clinical diagnosis of rabies. During the 10-year study period there were 575 patients (average 57.5 cases per year, range 57 to 119) with a final diagnosis of rabies. Most patients were male (n = 404, 70.3%) and aged ≥ 20 years (n = 433, 75.3%). Patients mostly came from the National Capital Region (n = 160, 28.0%) and the adjacent Regions III (n = 197, 34.4%) and IV-A (n = 168, 29.4%). Case mapping and heatmaps showed that human rabies cases were continuously observed in similar areas throughout the study period. Most patients had hydrophobia (n = 444, 95.5%) and/or aerophobia (n = 432, 93.3%). The leading causative animals were dogs (n = 421, 96.3%) and cats (n = 16, 3.7%). Among 437 patients with animal exposure history, only 42 (9.6%) had been administered at least one rabies vaccine. Two patients (0.5%), young children bitten on their face, had received and a full course of rabies vaccine. Human rabies patients were continuously admitted to the hospital, with no notable decline over the study period. The geographical area in which human rabies cases commonly occurred also did not change. Few patients received PEP and there were two suspected cases of PEP failure. The retrospective design of this study was a limitation; thus, prospective studies are required.

A prospective observational study of community-acquired bacterial bloodstream infections in Metro Manila, the Philippines.

Community-acquired bacterial bloodstream infections are caused by diverse pathogens with changing antimicrobial-resistance patterns. In low-middle income countries in Southeast Asia, where dengue fever is endemic and a leading cause of fever, limited information is available about bacterial bloodstream infections due to challenges of implementing a blood culture service. This study describes bacterial bloodstream pathogens and antimicrobial-resistance patterns in Metro Manila, the Philippines. We aimed to identify the proportion of patients with a positive blood culture, the bacteria isolated and their antimicrobial resistance patterns, and the clinical characteristics of these patients, in this dengue endemic area. We conducted a prospective observational study in a single hospital enrolling febrile patients clinically suspected of having a community-acquired bacterial bloodstream infection between 1st July 2015 and 30th June 2019. Each patient had a blood culture and additional diagnostic tests according to their clinical presentation. We enrolled 1315 patients and a significant positive blood culture was found in 77 (5.9%) including Staphylococcus aureus (n = 20), Salmonella enterica Typhi (n = 18), Escherichia coli (n = 16), Streptococcus pneumoniae (n = 3) and Burkholderia pseudomallei (n = 2). Thirty-four patients had meningococcal disease diagnosed by culture (n = 8) or blood PCR (n = 26). Additional confirmed diagnoses included leptospirosis (n = 177), dengue virus infection (n = 159) and respiratory diphtheria (n = 50). There were 79 (6.0%, 95%CI 4.8%-7.4%) patients who died within 28 days of enrollment. Patients with a positive blood culture were significantly more likely to die than patients with negative culture (15.2% vs 4.4%, P<0.01). Among S. aureus isolates, 11/20 (55%) were methicillin-resistant (MRSA) and ST30: USA1100 was dominant sequence type (88.9%). Antimicrobial-susceptibility was well preserved in S. enterica Typhi. Among hospitalized patients with clinically suspected community-acquired bacterial bloodstream infection in Metro Manila, the Philippines, 5.9% had a blood culture confirmed infection of whom 15.6% died. S. aureus, including a significant number of MRSA (USA1100 clones), S. enterica Typhi, E.coli and Neisseria meningitidis were frequently identified pathogens.

Comparative genomic analysis of Leptospira spp. isolated from Rattus norvegicus in Indonesia.

Leptospirosis is one of the most prevalent zoonotic diseases caused by pathogenic spirochetes of Leptospira spp. The disease has become a public health concern in urban localities in the tropics, where rats serve as significant reservoir animals for leptospirosis transmission. In Indonesia, the occurrence of leptospirosis is underestimated, and information on the causative Leptospira genotypes and serotypes is limited. This study reports the isolation of Leptospira spp. from rats captured in urban areas of Bogor, Indonesia. Serogroups and genotypes, sequence types (STs), or multiple-locus variable-number tandem repeat analysis (MLVA) types using 11 loci, were determined for the isolates. Furthermore, whole genome sequencing (WGS) was performed on 11 Indonesian isolates and 24 isolates from other Asian countries. Ninety small mammals, including 80 Rattus norvegicus and ten Suncus murinus, were captured and, 25 Leptospira spp. were isolated solely from R. norvegicus (31.3%). The isolates were identified as Leptospira borgpetersenii serogroup Javanica with ST 143 (four strains) and Leptospira interrogans serogroup Bataviae with the same MLVA type as isolates from other Asian countries (19); the serogroup of the two L. interrogans with ST252 could not be identified. The core genome SNP-based phylogenetic tree revealed that Indonesian isolates were genetically related to L. borgpetersenii serogroup Javanica strains widely distributed in Asian countries but formed a different cluster from other strains. The phylogenetic tree of L. interrogans serogroup Bataviae isolates from Indonesia, the Philippines, Taiwan, and Vietnam revealed that isolates were grouped into five clusters based on their geographic locations. This study discovered a high carriage rate of Leptospira spp. among R. norvegicus in Bogor, Indonesia, indicating a potential risk of rat-borne leptospirosis in the area. Besides L. borgpetersenii serogroup Javanica, WGS on L. interrogans serogroup Bataviae illustrated the geographical structuring of genetic diversity in Leptospira spp.

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.

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.

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.

Frequent Community Use of Antibiotics among a Low-Economic Status Population in Manila, the Philippines: A Prospective Assessment Using a Urine Antibiotic Bioassay.

The widespread unregulated use of antibiotics without medical consultation contributes to the burden of antibiotic resistance in Southeast Asian countries. This study investigated antibiotic use before hospital consultation. In a prospective observational study from February 2, 2015, to July 2, 2015, we enrolled febrile patients attending the emergency room in San Lazaro Hospital, Manila, the Philippines. A urine sample was collected and a bioassay was used to detect antibiotic activity in urine using Bacillus stearothermophilus (ATCC7953), Escherichia coli (ATCC25922), and Streptococcus pyogenes (ATCC19615). Patients or caregivers reported their medication history, clinical information, and socioeconomic status. During the study period, 410 patients were enrolled. The median (interquartile range) age was 14 (7-23) years and 158 (39%) reported prior antibiotic use, predominantly a beta-lactam antibiotic. A total of 164 (40%, 95% confidence interval [CI]: 35-45) patients were urine bioassay positive with any of three organisms. The Bacillus assay was the most sensitive, detecting 162 (99%, 95% CI: 96-100) cases. Among bioassay positive patients, dengue (N = 91, 55%, 95% CI: 48-63) was the most frequent diagnosis, followed by other viral infections, including measles, rubella, and mumps (N = 17, 10%, 95% CI: 6-16). Patients with a positive bioassay were significantly more likely to be from the lowest-income group (adjusted odds ratio [AOR]: 1.7; 95% CI: 1.1-2.6) and required hospital admission (AOR: 2.1; 95% CI: 1.3-3.5). Unnecessary antibiotic use for febrile illnesses before hospital consultation is common in a low-income, highly populated urban community in Manila. Education targeting this group should be implemented to reduce unnecessary antibiotic use.

HIV in the Filipino healthcare worker : A way forward

The unprecedented increase in HIV cases in the Philippines has not spared healthcare workers. Due to the severe stigma associated with this disease, healthcare workers (HCWs) with HIV face signification discrimination especially if they elect to continue practicing medicine. This article examines the evidence for occupation transmission of HIV from healthcare workers to patients and provides a framework for ethical testing of HCWs and a means to continue practice while preserving patient safety.

Prediction of response to treatment of chronic hepatitis B with pegylated interferon in the Philippines.

The response marker for interferon has not been investigated fully for hepatitis B viruses (HBVs) in the Philippines where novel subtypes B5 and C5 were recognized recently. The prediction parameters for interferon treatment were assessed, with emphasis on the mutation patterns in the basal core promoter and precore regions in patients with chronic hepatitis B. Seventeen HBeAg-positive patients were stratified according to response to treatment with pegylated interferon based on HBe seroconversion and HBV load. Intra-patient distributions of wild-type strains (A1762, G1764) and variants (T1762, A1764) were analyzed using HBV-DNA amplification and subsequent molecular cloning. The rate of variants (T1762, A1764) harbored by a patient was higher among responders (41.2% and 31% per person on average) than among non-responders (2.4% and 2.4%) to treatment with pegylated interferon at the baseline, respectively (P < 0.05). The rate of variants (T1762, A1764) harbored by responders (41.2% and 31%) decreased to 1.7% and 1.7%, and wild-type strains (A1762, G1764) conversely became majority (98.3% and 98.3%) after treatment with pegylated interferon, respectively. HBV strains harbored by two of six responders and a patient with lower baseline load (1.0 x 10(4) copies/ml) showed genotype shift from A to other genotypes, where genotype A disappeared preferentially after the loss of HBeAg and genotypes B and C formed a major population. These results suggest that the HBV variants (T1762, A1764) and HBV genotype A in the Philippines have an advantage in the response to pegylated interferon. These results warrant a large-scale examination for further precise prediction of the response to treatment with interferon.

Rapid spread of hepatitis C virus among injecting-drug users in the Philippines: Implications for HIV epidemics.

From the trends of human immunodeficiency virus (HIV) epidemics in South and Southeast Asia, it was postulated that an HIV epidemic would start as a blood-borne infection among injecting-drug users in the Philippines. In 2002, 560 individuals were recruited in Metro Cebu, Philippines and tested for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections. The seroprevalence of anti-HCV among injecting-drug users (70.1%, 61/87) was significantly higher than those among inhalation drug users (16.3%, 7/43; P = 0.00; OR = 12), sex workers (0%, 0/130; P = 0.00; OR = infinity), antenatal clinic attendees (0%, 0/100; P = 0.00; OR = infinity), and students/health care workers (2%, 4/200; P = 0.00; OR = 115). The seroprevalence of HBsAg among injecting-drug users (10.3%, 9/87) was significantly higher than those among sex workers (2.3%, 3/130; P = 0.01; OR = 4.9), and antenatal clinic attendees (3%, 3/100; P = 0.04; OR = 3.7), but was not statistically different from those among inhalation drug users (9.3%, 4/43; P = 0.9) and students/health care workers (4.5%, 9/200; P = 0.06). None of the study population was reactive to anti-HIV antibody. The HCV strains obtained from the injecting-drug users belonged to either genotype 1a or 2b and the strains in each genotype clustered closely to each other. There was no dual infection with genotype 1a and 2b. These results suggest that the HCV infection in injecting-drug users may be emanating rapidly from limited number individuals in Metro Cebu, Philippines.